Prof Didier Astruc

Jean-René Hamon

Sergio Moya

Danijela Gregurec

Joseba Irigoyen

Luis

Amalia Wang

Haibin Rapakousiou

Dong Gu

Na Wang

Sylvain Li

Roberto Gatard

Xiang Ciganda

Fangyu Liu

Qi Fu

Wang

Changlong Wang

Djamila Ikhlef

Samia Kahlal

Jean-Yves Saillard
email: saillard@univ-rennes1.fr

Didier Astruc
email: d.astruc@ism.u-bordeaux.fr

Lionel Salmon

Qian Li

María Echeverría Igartua

Roberto Ciganda

Jaime Ruiz

Y Mei

G Sharma

Y Lu

M Drechsler

T Irgang

R Kempe

Langmuir M Ballauff

Metal-catalyzed azide-alkyne "click" reactions: Mechanistic overview and recent trends

Keywords: Metal-Catalyzed Alkyne-Azide Cycloaddition Copper Click Mechanism CuAAC green chemistry, heterogeneous catalysis, ligand design, nitroarene reduction, transition metal nanoparticles

and Dr. Lionel Salmon for their supports over the last four years, for

General introduction

Nanoscience and nanotechnology involve studying and working with matter on an ultrasmall scale and deal with the exploration, characterization and application of nanostructured materials. This area has undergone great prosperity and has become an emerging field of research for which significant studies have revolutionized the nanosystems. [1] Promises and possibilities are wide-ranging; for instance, nanomachines will transform modern medicine to the search for cancer cells or to deliver drugs. [2] Nanomaterials have stimulated great interest in optical, electrical, and mechanical applications, and among them nanocatalysts [3] have opened new routes for drug developments, clean energy conversion, environmental decontamination and green chemistry for fine chemical production.

Homogeneous catalysts are usually solubilized in the reaction media and are very efficient, selective, and industrially useful, but they suffer from lack of recovery, reusability and limited thermal stability. [4] On the other hand, heterogeneous catalysts benefit from easy recovery from reaction media and possible use of high temperatures, but they suffer from selectivity problems and lack of mechanistic explorations.

Furthermore, green catalysis, [5] that is critically addressed by the principles of green chemistry, is an important issue in modern chemical processes. Features of the green catalysts ideally involve low preparation costs, high activities, good selectivities, high stabilities, efficient recovery, and good recyclability. Green catalysts should efficiently catalyze reactions in "green" solvents (e.g., neat condition, water, ethanol). Finally the design and applications of green catalysts is not only a task of great economic and environmental importance in catalysis science, but also should overcome the problems of metal contamination in products.

Nanocatalysis is defined by catalysis using nanoparticles (NP). [3] The catalytically active NPs have sizes between the order of one nanometer (nm) and several tens or hundreds of nanometers, but the most active ones in catalysis are only one or a few nanometers in diameter (containing a few tens to a few hundred atoms).

They have a high surface-to-volume ratio and a large proportion of surface atoms, i. e. predominantly edge and corner atoms that are very active for substrate activation.

Since around the beginning of the 1990's, this area of catalysis has become an independent field usually called colloidal catalysis or quasi-homogenous catalysis since it was believed, at that time, to be a bridge between classical homogenous catalysis and heterogeneous catalysis. In this regard, nanocatalysis combines the positive aspects of both homogenous catalysis (high catalytic activity and selectivity, and mechanistic studies leading to catalyst improvements) and heterogeneous catalysis (easy catalyst separation from reaction media and good recyclability). [4] In this context, transition metals based nanomaterials are of particular interest in the utilization of nanocatalysts. [6] Transition-metal-based heterogeneous nanomaterials contain the catalytic species that perform substrate activation, and the catalytic reaction proceeds on the supported metal surface thereby bringing about selectivity and efficiency. In order to obtain nano-sized catalytically active NPs, transition-metal NP size must be restricted to a few tens to several thousand metal atoms. Therefore these transition-metal NPs need be stabilized by dendrimers, polymers, ionic liquids (ILs) and inorganic solid supports such as silica, alumina, zirconia, carbon, etc. Indeed, stabilizers are playing a crucial role and eventually affect the catalytic properties. [7] For instance some strong ligands (thiolates, phosphines, phosphine oxides, etc.) inhibit the active surface sites, leading to negative catalytic effects on the catalytic reactions occuring at the NPs surface. Thus, "green" ligands that involve mild NP stabilization in water and are easy to displace and eventually provide more surface active sites in catalytic processes are searched to further improve activity. This is the case for instance with nitrogen donors (e. g. amines or 1,2,3-triazole based ligands) that leave the metal site at the metal surface in the zero oxidation state without back bonding, i.e. electron rich, which is potentially most favorable for catalysis. On the other hand, "ligand-free" supported nanocatalysts represent another promising alternative compared to traditional nanocatalysts, because the absence of ligand enables "clean" NP surfaces that mostly expose the edge and corner active atoms that usually are very efficient to activate substrates. Indeed, the rational synthesis of ligandless, ultrafine and efficient nanoparticle catalysts is an ongoing challenge.

Before this PhD our research group has examined dendrimers and transition-metal NPs as templates for homogeneous and heterogeneous catalytic reactions. [8] We have extended the principle of dendritic templated nanocatalysis to ligand-induced nanocatalysis including the use of amphiphilic triazole (click) nanomaterials for improved nanocatalysis. Thus the present PhD thesis deals with the design and application of transition metals based nanomaterials as new nanocatalysts in a variety of chemical reactions with the aim to nano-engineer NP size and supporting environment in order to improve the catalytic activity, stability, recovery ability and to decrease the catalyst loading.

In the first chapter, a review is presented to generally introduce the mechanistic aspects and recent trends of the metal-catalyzed azide-alkyne cycloaddition reactions [9] with catalysts based on various transition metals. The copper-catalyzed alkyne-azide cycloaddition (CuAAC), [10] click reaction, forming 1,2,3-triazole based ligands, is the most used one and has revolutionized molecular engineering including applications to organic and medicinal chemistry, polymer science and materials science.

In the second chapter, a new concept based on the design of amphiphilic ligand that mimics the functions of dendrimers to stabilize various transition metal nanoparticles was firstly proposed. This tris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand containing three clicked triazole rings and a PEG 2000 chain is synthesized through CuAAC and a Williamson reaction. These amphiphilic ligand-transition metal nanoparticles are very efficient nanocatalysts with part per million (ppm) loadings for 4-nitrophenol reduction, click reaction, Suzuki-Miyaura reaction and transfer hydrogenation reaction. [11] Moreover, we also compared the stabilization of AuNPs by mono-, bis-, and tris-trz and their influence of the trz denticity on the 4-nitrophenol reduction by NaBH 4 in water also including comparison with current polyethylene glycol 2000 (PEG) and polyvinylpyrrolidone (PVP) AuNP stabilizers. Further, based on this ligand, especially the utilization of the chelation of the triazole groups, an efficient amphiphilic "click" Cu I catalyst in water is designed. This catalyst shows high activity for CuAAC "click" reaction in water at ambient temperature with catalyst loading at only ppm levels for the synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties. [12] The third chapter first reports the preparation of ultrafine and monodispersed bimetallic RhAg nanoparticles (NPs) that are uniformly supported on reduced graphene oxide nanosheets (RhAg/rGO). The bimetallic RhAg NPs involve a synergy between the two metals on rGO that improves the catalytic activity compared to both monometallic counterparts. The catalyst was recycled, and its amount was reduced to ppm level while retaining an exceptional catalytic efficiency in the 4-NP reduction by NaBH 4 in water at room temperature. [13] Secondly, the supramolecular H-bonding interactions between the PEG termini of the tris-trz-PEG ligand and the functional groups of the graphene oxide (GO) support enables the design of new heterogeneous α-Fe 2 O 3 nanocluster/GO catalysts, which showed not only high efficiencies towards 4-nitropheol reduction and Suzuki-Miyaura reaction, but also can be recovered and reused without significantly loss of catalytically active NPs and activities. [14] More importantly, highly efficient ligand-free nanocatalysts synthesis based on the redox reaction between transition-metal cations and GO providing transition metal NP/GO nanocatalysts and their use in water under ambient conditions for a variety of reactions. The high efficiencies of such noble-metal as well as biometal composites as excellent green catalysts are exemplified for the 4-nitrophenol reduction, the hydrolysis of ammonia-borane (AB) for H 2 generation in water, the Sonogashira reaction and the click reaction. [15] The fourth chapter demonstrates the highly dispersed ligand free Ni NPs have been successfully synthesized using zeolitic imidazolate framework as nanocatalyst template, exhibiting remarkably high catalytic activity for hydrogen generation from hydrolysis of ammonia-borane. [16] By the mechanistic studies, ion effect is further discovery the in this reaction, which allows the remarkable improvement of the catalytic performance and the controlled release of hydrogen.

At the end of the thesis, the "Conclusion and Perspectives" section summarizes the progress resulting from the research conducted during this thesis concerning the design and application of transition metal based nanocatalysts for various chemical reactions. Thereafter, perspectives are provided, indicating that development of new heterogeneous nanocatalysts for instance the exploration of bimetallic catalysts, and earth abundant metal (so-called "biometals") catalysts, should be valuable research directions of further work along this line. In turn, the theoretical advances could guide and lead chemists to imagine new reaction improvements.

Introduction

The concept of "click chemistry" proposed by Kolb, Finn and Sharpless in 2001 [1] has revolutionized molecular engineering including applications to organic and medicinal chemistry [2][3][4][5][6][7][8][9][10][11], polymer science and materials science [12][13][14][15][16][17][18][19][20][21]. Among the various "click" reactions responding to the requirements of this concept, the most generally used one is the copper(I)-catalyzed reaction between terminal alkynes and azides (CuAAC) selectively yielding 1,4-disubstituted 1,2,3-triazoles, that was reported independently by the Sharpless-Fokin [22] and the Meldal groups in 2002 [23,24]. This reaction is the catalyzed version of the 1,3 dipolar cycloaddition, known in the former decades as the Huisgen reaction that had already been first disclosed in the XIXth century [25]. The advantages of the Cu(I) catalyzed "click" reaction are that (i) it is regioselective, whereas the non-catalyzed Huisgen reaction lacks regioselectivity, producing both the 1,4-and 1,5-disubstituted isomers, (ii) it proceeds at milder temperature than the non-catalyzed reaction (iii) it fulfills the requirements of "green chemistry" in so far as it can occur in aqueous or alcoholic medium, (iv) the catalyst reported by Sharpless and Fokin is simple and inexpensive; it consists in CuSO 4 •5H 2 O + sodium ascorbate, the later reagent being fine for the reduction of Cu(II) to Cu(I), but not to Cu(0) [22]. The only drawback is the need of large quantities of this catalyst mixture that is slow. Indeed, various nitrogen ligands accelerate the Cu(I) catalysis of the "click" reaction and allow using 1% or a few % Cu (I) catalyst [20,26]. Recently we reported that using a recyclable dendritic nanoreactor in water only, it was possible to decrease the Cu(I) amount using the CuSO 4 •5H 2 O + sodium ascorbate catalyst to 1 ppm or only a few ppm with various applications to biomedical targets [27a]. Disubstituted alkynes cannot be used for the CuAAC reaction, because deprotonation of the terminal alkyne to give Cu(alkynyl) intermediate species is mandatory in this reaction [26]. With pentamethylcyclopentadienyl-ruthenium catalysts, however, the Fokin group showed that the other isomer, i.e. 1,5-disubstituted triazole is regioselectively formed in the RuAAC reaction even with disubstituted alkynes according to a different mechanism [28]. Ruthenium catalysis is versatile, because other ruthenium catalysts reacted with terminal alkynes via a key ruthenium-acetylide species to yield the 1,4-disubstituted triazoles [29]. Since the early reports, a variety of transition-metal catalysts have been used for the reactions between mono-or disubstituted alkynes and azides (vide infra). For the Cu(I) catalyzed reaction, a variety of mechanisms involving Cu(I)-aryl intermediates have been proposed in which the key-step species contains either mononuclear [35] or binuclear copper species [30][31][32][33][34][35][36][37][38]. Theoretical studies of the RuAAC reaction have also been reported [28,[39][40][41]. Given this mechanistic variety and the large number of transition-metals catalysts used for the MAAC reactions (M = transition metal), it is essential and timely to address the mechanistic problems by reviewing the state of knowledge in the literature, conduct theoretical calculations on MAAC reactions and compare these results with those reported in the literature.

MAAC reactions with various metal catalysts

The CuAAC reactions

With over 2000 publications in hardly more than a decade, the CuAAC reaction is illustrious and undoubtedly has been a breakthrough in organic synthesis and Cu(I) catalysis 42]. Although a large number of Cu(I) catalysts are efficient in catalyzing this reaction [21,24,26], the conventional Sharpless-Fokin catalyst (CuSO 4 /sodium ascorbate) [22] is by far the most used one in spite of the large required catalyst amount, slow rate, difficulty to remove copper after the reaction, and sometimes the detrimental effects on rates and yield observed in the presence of chlorides, bromides and iodides [43]. For instance, low efficiency was observed for CuAAC of 2-azidopyridines [44]. Thus experimental protocols such as adding podand-like ionic liquids (ILs) [45], simple thermal heating [46], ultrasound-assistance [47], and the combination of both ultrasounds and ILs [48] were used to accelerate the reaction rates of the Sharpless-Fokin catalyst.

Concerning the optimization of "X" ligands in the Cu(I)(X) catalysts, Zhang et al. compared various Cu(I) sources (CuCl, CuBr, CuI, CuSO 4 •5H 2 O/NaAsc and [(CuOAc) 2 ] n ) that catalyze the CuAAC reaction of 6 tetrazolo- [1,5-a]pyridines toward the synthesis of 1-(pyridin-2-yl)-1,2,3-triazoles, and the results showed that copper(I) acetate was the most efficient catalyst [49]. The nitrogen ("L") ligands accelerate the CuAAC reaction are amines, pyridines, and triazoles, in particular tridentate ligands [26,[50][51][52]. N-heterocyclic carbenes (NHC) that were reported by Nolan's group to be excellent ligands, providing high reaction rates and yield for the CuAAC reaction (vide infra). Interestingly, internal alkynes were also successfully used, which suggested that a different mechanism than that implying copper-acetylide intermediates was involved [33,53]. Bertrand's mesoionic carbenes were also efficient [54,55] even with sterically hindered azide and alkynes [55]. With various ligands and Cu(I) catalysts, a large variety of solvents have been used, and the reaction is compatible with aqueous solvents [21,22].

Noticing the fact that the Cu(I) species accelerated the rate of the AAC reactions by 7-8 orders of magnitude compared to purely thermal cycloaddition reactions observed without metal catalysts, Sharpless and coworkers then proposed a stepwise mechanism involving a mononuclear Cu-acetylide intermediate based on DFT studies (top of Fig. 1) [31]. In a latter study, however, Fokin and Finn also pointed out the possibility that two Cu centers were involved in the transition state of the cycle [32], for which the following detailed kinetic studies confirmed the possibility of a ,-bimetallic Cu(I) intermediate [26,50,56]. Subsequent DFT calculations, carried out in the same group [22b,57], supported this hypothesis by showing that the complexation of the alkyne unit by a second metal center (bottom of Fig. 1) reduces the activation energy barrier by 4-6 kcal/mol, depending on the nature of the ligand on the Cu B atom indicated in Fig. 1 [57]. The effect of -complexation of the -alkynyl-Cu(I) species enhances the reactivity of the alkynyl ligand by decreasing electron density on the sp carbon atoms, thus facilitating the azide attack. In fact the 2 coordination mode of the alkyne to Cu B was quite distorted and dependent on the ligand nature. Concomitantly to the DFT investigation on binuclear processes of Fokin and coworkers [57], Straub published a computational investigation on copper acetylide complexes showing the same trend, i.e., di-and tetra-nuclear species display higher reactivity in the CuAAC reaction than do their mononuclear relatives [58a]. According to this study, the complexation of a supplementary copper atom reduces the Cu C C double bond character and therefore the ring strain in the metallocyclic intermediate. Following previous work [58b], Straub's group also recently presented the first molecular copper acetylide complex that featured high activity in CuAAC with added acetic acid even at -5 • C. The relationship between the "click" reactivity and the aggregation of acetylidecopper species different from dinuclear intermediates contributes to the mechanistic interpretation of this reaction. Indeed, complexes with acetylide ligands that bind copper species may be resting states of the catalyst in such click reaction mixtures that are not acidic [58c].

Following these pioneering computational works, several theoretical mechanistic investigations on the CuAAC reactions have been carried out, considering various copper systems, most of them multinuclear, and leading basically to similar qualitative conclusions [34,[58][59][60][61][62]. A recent investigation pointed out the possibility for a concerted vs. stepwise nature of the mechanism, however, depending on the ligand nature [63]. The most recent experimental mechanistic study by Fokin's group unambiguously demonstrated the participation of a dinuclear copper intermediate in the case of a CuAAC reaction in which a mixture of Cu(I)(aryl) complex and [Cu(I)(MeCN) 4 ] + was used (Fig. 2). Their study revealed that Reprinted with permission from Ref. [57]. Copyright 2007, American Chemical Society. Reproduced with permission from Ref. [38]. Copyright 2013, American Association for the Advancement of Science. monomeric copper acetylide complexes were not reactive toward organic azides, except in the presence of exogenous copper catalyst [38]. Furthermore, direct injection by time-of-flight mass spectrometry (TOF-MS) for crossover experiments with an isotopically enriched exogenous copper source showed that two copper centers were involved within the cycloaddition process yielding the 1,4-substituted 1,2,3-triazoles. This mechanism was also recently confirmed by ESI-MS upon utilizing a mixture of an approach of neutral reactant and the strategy by Angelis's group that involves ion tagging and characterized the putative dinuclear copper intermediates [64].

The CuAAC reaction is also working well with the mononuclear mechanism as shown by efficient intradendritic catalysis that cannot accommodate two metals at the active site for obvious steric reasons. Intradendritic catalysis with the Cu catalytic center located either at the dendrimer core or activated by the triazole ligand located on the dendrimer tether is so efficient that sometimes down to a ppm amount of Cu is enough to catalyze the CuAAC reaction in water at ambient temperature [27a]. In the case of the active Cu(I)tren catalyst, a dendrimer was constructed around the tren ligand with Cu at the metallodendrimer core, emphasizing the monometallic mechanism. In such cases, the proposed mechanism based on DFT calculations [27b] involves the following intermediates (Fig. 3):

With a NHC-Cu(I) catalyst, however, DFT calculations by Nolan's group confirmed that a different mechanism was operating taking into account the reactivity of internal alkynes [33]. The following research from this group reported that, with the version of the NHC ligands bearing N-adamantyl substituents, the Cu-iodide catalyst was always superior to other [Cu(NHC)X] complexes in water or under neat conditions [65]. Based on the fact that the transformations involved both terminal and internal alkynes, these authors proposed a multiple mechanistic pathways for AAC reaction that suggested that the alkyne (or acetylide following deprotonation) might bind either end on or side on to Cu (Fig. 4) [66]. Moreover, the addition of aromatic nitrogen donors to the reagent mixture increased the AAC reaction activity, as reported by Gautier's group [67]. Furthermore, Nolan's group also pointed out the importance of NHC salts formation in the investigation of the cationic bis-carbene complexes for AAC. Indeed, the positive role of the second NHC ligand for the deprotonation of the terminal alkynes favors the generation of a [Cu]-acetylide species that plays a key role for AAC [68a].

Recently, the Bertrand group compared the role of the anionic ligand in each individual step of the AAC reaction catalyzed by LCuX by examining the kinetic profiles on these stoichiometric reactions [68b]. The X ligands covered a broad range of basicity (X = Cl, OAc, OPh, Ot-Bu, OTf), and the L ligand was Bertrand's cyclic (alkyl)(amino)carbene (CAAC). In these cases, the steps are the metallation of the terminal alkyne, the formation of the ,-alkyne bis(copper) complex, the cycloaddition producing the metallated triazole, and the protolysis of the latter that regenerates the active 11 Fig. 3. Computed intermediates and transition state involved in the mechanism of Cu(I)(tren)-catalyzed CuAAC reactions. Reproduced with permission from Ref. [66]. Copyright 2013, Royal Society of Chemistry.

catalytic species and produces the final triazole. Phenyl acetylene and benzyl azide were used as substrates. The results remarkably pointed out the Janus role of the X ligands. Basic X ligands favored the metallation, but disfavor the formation of the dinuclear intermediate, opposite to non-nucleophilic ligands. Acetate was a good compromise and very efficient for the proto-demetallation step. That the dinuclear Cu species can be disfavored in the CuAAC mechanism is also an interesting result at variance with other studies [68b].

In the CuAAC reactions, one of the interesting ways to generate Cu(I) appeared recently is by Cu(II) photoreduction simply activated using light to induce the click reactions. Tasdelen, Yagci and Ramil et al. have reviewed these applications, especially toward biomolecular systems and macromolecular syntheses [69], The mechanisms of photoinduced CuAAC "click" reactions involved the direct (i) and indirect (ii) reduction pathways of Cu(II) to Cu(I). The photo-click chemistry using visible light requires a radicalgenerating photoinitiator that assists photoreduction of Cu(II) to reactive Cu(I) species for the CuAAC reaction (Fig. 5, route a) as demonstrated by Bowman's group [70]. For example, upon irradiation at 350-520 nm, the presence of an additional photoinitiator is not necessary when the solvent contains at least 15 wt% of methanol that serves for the photoreduction process [71]. Another technique consists in the direct photolysis of the Cu(II) complex to generate Cu(I) by UV light irradiation, because many Cu(II) complexes such as CuCl 2 /PMDETA [70b,70d,70e,72], Cu(AP) 2 -PMDETA [70c], Cu(II)-PAC complex (PAC = polynuclear aromatic compound) [73], Cu(II)/carboxylate complex [74], and copper(II)-DMEDA complex [75] are sensitive to UV light or sunlight. Here the ligand is involved, i.e. it absorbs the UV light, promoting intramolecular electron transfer from the -system of the ligand to the central Cu ion (Fig. 5, route b). During this process, Cu(II) is reduced to Cu(I) and the ligand is transformed into a radical species [76]. Interestingly, recently doping small amounts of Cu into the ZnS quantum dots (QDs) shell partially quenched the QD core (CdSe) luminescence, making QDs photoactivated vectors for the release of catalytically active Cu + ions for CuAAC [77]. On light irradiation, the QDs photooxidized with S was oxidized to SO x y-, causing Cu to form a complex with the azide that acted as a sacrificial electron acceptor allowing the click reaction to occur.

The other interesting ways to generate catalytic active species Cu(I) by using Cu(0) NPs is through comproportionation of Cu(0) and Cu(II) in the native oxide layer on the Cu surface [78]. In Alonso's proposed mechanism for the CuNP-catalyzed AAC, Cu(I) acetylides appeared as the true intermediate species [79]. The in situ generation of CuCl was postulated after acetylene deprotonation, with the concomitant formation of triethylammonium chloride (in the presence of LiCl derived from CuNPs preparation), and the action of the latter on the CuNPs. The reaction of the nascent CuCl with the acetylide species would furnish the corresponding copper(I) acetylide (Fig. 6) [80]. From this point of view, the reaction mechanism followed the original stepwise pathway that was proposed by Noodleman, Sharpless and Fokin et al. [31].

The RuAAC reactions

Apart from copper, the most frequently used catalysts for the MAAC reactions are ruthenium-based catalysts, the reaction being then abbreviated as RuAAC. Among all the Ru catalysts, the most investigated ones are the pentamethylcyclopentadienyl ruthenium chloride-based (noted [Cp*RuCl]) complexes), although Fokin's group also observed that the steric encumbrance imparted by the Cp* ligand is detrimental to the reaction [81]. These complexes catalyzed the regioselective RuAAC reaction of terminal alkynes forming, unlike CuAAC catalysts, 1,5-disubstituted 1,2,3-triazoles, and also unlike the CuAAC catalysts, they reacted with internal alkynes providing trisubstituted 1,2,3-triazoles [28,39,40,82]. The Cp*RuCl based catalysts provided multiple application that were recently developed (vide infra) [81,[83][84][85][86][87].

The first mechanistic investigation was proposed by Lin, Jia, Fokin and coworkers based on DFT calculations [39]. The firstly formed azide-alkyne Ru complex was suggested to lead to a 6-membered ruthenacycle intermediate, followed by reductive elimination and formation of the triazole product. Subsequent calculations by Poater, Nolan and coworkers [88] found a somewhat different pathway but confirmed the key ruthenacycle intermediate. Their computed mechanism is reproduced in Fig. 7. More recently, Boz and Tüzün published a detailed DFT study in which various terminal and internal alkynes as well as Cp and Cp* ligands were considered [41]. They investigated the various possible mechanisms ensuing from the four possible configurations of the azide-alkyne Ru precursor complex. This detailed investigation allowed them to evaluate the interplay between the various electronic and steric effects. In any case the formation of a key 6-membered ruthenacycle intermediate is confirmed. Their computed regioselectivities (particularly in the case of internal alkynes) reproduce the experimental ones.

Given the richness of ruthenium catalysis, other families of ruthenium catalysts were disclosed. The Jia group first reported the RuAAC of terminal alkynes with 100% selectivity to lead to 1,4disubstituted 1,2,3-triazoles using the catalyst [RuH 2 (CO)(PPh 3 ) 3 ] [29,89]. Then they compared a family of Ru catalysts that do not contain Cp ligands for the RuAAC reaction of terminal alkynes to selectively yield 1,4-disubstituted 1,2,3-triazoles [29], and the most efficient catalyst was [RuH( 2 -BH 4 )(CO)(PCy 3 ) 2 ]. Both the experimental results and the DFT calculations indicated that the active species in the reactions was [Ru(C CR) 2 (CO)(PR ′ 3 ) 2 ] (Fig. 8). In their proposed mechanism, the authors indicated that the Ru-acetylide species 1 first formally underwent a cycloaddition reaction with an azide to give the species [Ru(triazolyl)], 2 (Fig. 8) resulting from initial coordination of the azide to the Ru center in 3 via the internal nitrogen atom (Fig. 9). Then, with a terminal alkyne metathesis of the Ru C bond occurred via a four-centered transition state yielding the 1,4-disubstituted 1,2,3-triazole, which regenerates the starting catalyst. The complete mechanism of this catalytic cycle proposed by Jia, Lin, Fokin, and coworkers [29] from a detailed DFT analysis of the mechanism with propyne, methylazide and [Ru(CCMe) 2 (CO)(PMe) 2 ] is shown in Fig. 9. These authors showed also that the formation of the 1,5-triazole is highly disfavored. This is in line with Boz and Tüzün's theoretical work (see above) that indicated the importance of the electronic and steric effects for Reproduced with permission from Ref. [29]. Copyright 2012, American Chemical Society.

13 Fig. 9. DFT free energy profile (in kcal/mol) for the proposed mechanism of the formation of 1,4-triazole catalyzed by a Ru complex lacking cyclopentadienyl ligand. Reproduced with permission from Ref. [29]. Copyright 2012, American Chemical Society.

the regioselectivity, both thermodynamic and kinetic parameters playing a crucial role in the reactions [41].

Lo's group presented the first case of ruthenium azido complexes catalyzing the cycloaddition reaction of terminal alkynes with alkyl azides [90,91]. The new ruthenium azido complexes were synthesized from the mother TpRu complex [Ru(Cl)(Tp)(PPh 3 ) 2 ], Tp = HB(pz) 3 , pz = pyrazolyl), yielding first [Ru(N 3 )(PPh 3 )[Tp( t BuNC)] [90], then the amine-substituted ruthenium azido complex [Ru(N 3 )(Tp(PPh 3 )(EtNH 2 )] [91]. Although the detailed mechanism could not be established, the authors speculated a similar mechanism to previous proposed by Fokin et al. [28]. As shown in Fig. 10, the displacement of the spectator ligands (EtNH 2 , PPh 3 ) produced the activated intermediate A that was then converted to the intermediate B via the oxidative coupling of an alkyne and an azide. After that, ligand substitution occurred in B leading to the release of the aromatic triazole product and regenerating the catalyst. Interestingly, in both cases, the N 3 ligand in the ruthenium azido complex did not couple the terminal alkyne in the substrate, because reaction energy for conversion of A to B is much smaller than that for conversion of A to C (DFT-computed free energies -45.9 kcal/mol vs. 34.9 kcal/mol, respectively) [91].

The AgAAC reactions

In a seminal report McNulty's group published the first example Ag(I) catalyst of the AAC reaction without copper at room-temperature (r.t.) [92]. Silver(I) salts alone were not efficient to promote the AAC reactions, but when AgOAc reacted with the P,O-ligand 2-diphenylphosphino-N,N,-diisopropylcarboxamide, the P,O ligand-silver(I) complex catalyzed the AAC reaction very well. Further experiments indicated that silver acetylide intermediate activated the formation of an acetylide-azide species toward cyclization [93]. Thus a reaction mechanism for homogeneous Ag(I)-catalyzed AAC reaction was proposed (Fig. 11). First of all, the loss of acetate from the 18-electron species 9 yield the active Ortega-Arizmendi et al. also reported an "abnormal" NHC complex, Ag(I)-aNHC, that catalyzed the ACC reactions [94]. In this case, silver chloride by itself catalyzed the cycloaddition of various alkynes and azides in good yield, however with side reactions. Further introduction of the aNHC ligand avoided side reactions and facilitated the purification of the final products. Hybrid AgNP catalysts were also developed. For example, Salam and co-workers recently reported that the AgNP/graphene oxide (Ag/GO) based composite catalyzed multi-component reactions and one-pot click reaction (Fig. 12). In their approach, the catalysts were very stable and showed no silver leaching or aggregation, and were reused at least 5 times without loss of catalytic activity [95]. However when the AAC reaction is said to be catalyzed by Ag-based catalysts or other metal catalysts, caution is appropriate, because trace amount of copper contaminants could be enough to catalyze the AAC reactions. Indeed, Connell et al. found that the successful cycloaddition of an azide and terminal alkyne catalyzed by the isolated complex [Ag 2 (L 1 ) 2 ](BF 4 ) 2 ] was actually catalyzed by trace amounts of copper in the catalyst [96].

Ferretti et al. recently reported that silver(I) oxide nanoparticles (Ag 2 O NPs) catalyzed AAC reactions in anhydrous toluene [97]. Although the Ag 2 O catalyst was less efficient than the conventional Cu I catalyst that was generated from the Cu(0) and CuO under the same condition, the Ag 2 O NPs are somewhat effective, robust and reusable, especially in the presence of a small amount of water. In this case, substituent effects were noticed, and substrates containing electron-withdrawing groups onto the azide moiety gave mixtures of regioisomeric cycloadducts, which was a limitation. One should recall here that the uncatalyzed Huisgen reaction that yields such mixtures of isomeric cycloadducts works under ambient or mild conditions when substrates possess electron-withdrawing groups [25]. Sarma's group then compared various silver sources in AAC reactions conducted in H 2 O/ethylene glycol (EG) under ambient conditions without exclusion of air [98]. The ligands and solvents played a critical role in their approach. Upon optimization the combinations of AgN(CN) 2 as a catalyst and DIPEA as a base/ligand gave the best results. It was proposed that this ligand played the same role as the tertiary amine in CuAAC reactions in the intermediate step. Various 1,4-disubstituted-1,2,3triazoles were synthesized in high isolated yield under these very mild conditions, showing that AgN(CN) 2 /DIPEA is a highly effective catalytic system for the AAC reactions.

The AuAAC reactions

"On-surface" chemistry was a viable method to synthesize covalent nanostructures under ambient temperature at the surface under ultra-high-vacuum (UHV) conditions [99]. This method has also been used to explore the mechanism of AAC reaction and guide the catalyst design. Bebensee et al. recently reported the fully regioselective AAC reaction on a Cu(111) surface leading to 1,4-triazoles (Fig. 13a) resulting from copper acetylide formation subsequent to C H activation and bonding of the alkynyl group to the Cu(111) surface. The reaction proceeded with a very low yield. Therefore XPS showed that significant degradation of the azide upon adsorption occurred on the surface, though the reaction proceeded readily; especially the intact reactants were available on the surface [100]. Using on-surface chemistry under UHV, Arado et al. explored the MAAC reaction on Au(111) (Fig. 13b). By combining cryogenic scanning tunneling microscopy (STM) and DFT studies, they confirmed Bebensee's results on Cu(111) (vide supra) according which the MAAC reaction occurred on the [100] surface. However, the difference between these two examples is Reproduced with permission from Refs. [100] and [101], respectively. Copyright 2013, American Chemical Society.

that Au (111) is not catalytically involved in C H activation of alkyne. It only played a role as a two-dimensional (2D) surface to place the two partners of the reaction, which provided the observed selectivity. The successful control of the regioselectivity of the MAAC by surface constraint together with the careful design of the reactants provided the effective well-defined nanostructure without the requirement of a catalyst or additional thermal activation [101]. Recently another particular case using a heterogeneous reusable Au/TiO 2 nanostructure to efficiently catalyze the AAC reaction was highlighted (Fig. 14a). The authors proposed a mechanism in three steps (Fig. 14b): (i) a gold atom (I) reduced the electron density on the alkyne, enabling facile nucleophilic attack by the azide; (ii) a six member intermediate II, then intermediate III formed (iii) gold was removed to afford 1,4-disubstituted 1,2,3-triazoles and complete the reaction cycle [102].

The IrAAC reactions

The Iridium-catalyzed intermolecular AAC (IrAAC) has also proved to be a valuable complement to the well-known CuAAC and RuAAC reactions. The dimeric iridium complex [Ir(cod)OMe] 2 catalyzed the direct formation of new 1,4,5-trisubstituted triazoles [103]. [Ir(cod)OMe] 2 catalyzed the AAC reaction bromoalkynes producing 1,5-disubstituted 4-bromo-1,2,3-triazoles under mild conditions (Fig. 15). The electronic features of the alkyne Reprinted with permission from Ref. [103]. Copyright 2013, American Chemical Society.

component strongly affected the reaction yield, i.e. the arylalkynes that are electron rich showed the optimized reactivity, while the bromoalkynes that are electron deficient provided a low yield of the corresponding 4-bromotriazoles. This catalyst was used to prepare 1,4,5-trisubstituted triazoles subsequent to Pd-catalyzed Suzuki-Miyaura reactions with appropriate arylboronic acids. Ding et al. compared various Ir complexes in the IrAAC of electron-rich internal alkynes and showed that the use of [Ir(cod)Cl] 2 optimized the reaction [104]. The increase of steric hindrance on the alkyne did not affect the reaction efficiency, but an electronic effect was also observed, i.e. electron-deficient alkynes led to moderate or good efficiency, while electron-rich and normal alkynes showed low reactivity except the aryloxy alkyne and selenyl alkyne.

These differences in the regioselectivities of addition of thioalkynes and bromoalkynes to azides have been elegantly rationalized through DFT calculations by Lin, Jia and coworkers [105]. Their major findings are summarized in Fig. 16. Both mechanisms start with the precoordination of the alkyne and azide on the metal center of [Ir(cod)X]. In the case of thioalkynes, a metallabicyclic Ircarbene intermediate, stabilized by the -donor effect of the 2 RS substituent is formed. In the case of bromoalkynes this -donor effect is much weaker, and the metallabicyclic intermediate cannot be stabilized. Rather, a six-member metallacycle intermediate is formed and, depending on the -donating ability of the R substituent, the 4-or the 5-bromotriazole is formed preferentially, as sketched in Fig. 16.

The NiAAC reactions

Rao's group recently demonstrated that the Raney Ni, without additional reducing agent, efficiently catalyzed acetylene azide cycloaddition reactions to form 1,2,3-triazoles [106]. In their methodology, the Raney nickel catalyzed combinatorial NiAAC with excellent yield. (Fig. 17a) To explore the NiAAC reaction pathway, deuteration experiments were conducted (Fig. 17b) in the presence of Ni(0) indicating that, unlike the copper-acetylide formation in CuAAC, the cycloaddition went through a metallocycle [107]. Thus in their proposed mechanism, the reaction starts on the Raney nickel surface by acetylene complexation leading to the -complex 11 (Fig. 17b). Then the reaction proceeds AAC leading to 13 via 12, and the Ni-acetylene species led to AAC in the orientation shown in 14. The authors suggested that stereoelectronic features of the azide and alkyne favor the transition states 12 or 14 leading to the 1,4-product preferred to 1,5.

The ZnAAC reactions

For the ZnAAC reactions, pioneering contribution by Chen's group showed that heterogeneous zinc-on-charcoal (Zn/C) catalyzed the cycloaddition of aryl/aliphatic azides and aryl alkynes (including internal alkynes) in DMF at 50 air (63-94% yield) (Fig. 18) [108]. In this case, no electronic effect was observed, both electron-rich and electron-poor azides generating similar good reaction yield. The catalyst was recovered and reused for at least five times without significant decrease of activity. When ZnNPs were alloyed with CuNPs to form the catalysts for multicomponent 1,2,3-triazole synthesis/triazole alkynylation, the presence of Zn resisted the oxidation of Cu by sacrificial formation of ZnO that played a role in controlling the formation of alkynylated triazoles [108].

On the other hand, Greaney's group also described a mild method for the regioselective formation of 1,5-substituted 1,2,3triazoles upon using ZnEt 2 at r.t [109a]. In their approach, the base N-methylimidazole (NMI) was needed to help the formation of the zinc acetylide species in order to promote reactivity and continue screening. The 4-position of the triazole was substituted via the aryl-zinc intermediate toward further coupling. The proposed mechanism for this reaction is summarized in Fig. 19. The initial metallation of the alkyne mediated by the amine base formed the zinc acetylide 16. Then the reversible pre-coordination between the azide and zinc acetylide occurred before the [3 + 2]-cycloaddition, after which the aryl-zinc intermediate 15 formed, then was utilized to lead to 1,4,5-trisubstituted 1,2,3-triazoles. Based on these experimental results, Lan's group then reported their DFT calculations toward the mechanism and regioselectivity research of this ZnAAC using frontier molecular orbital (FMO) theory and distortion-interaction energy analysis [109b]. B3LYP-D3BJ calculations showed that ethynylzinc complexes bearing alkyl substituents showed a reactivity analogous to that of ethyl(phenylethynyl)zinc and a lower regioselectivity. B3LYP calculations gave a higher regioselectivity, however, because of a lower distortion energy in the transition state and led to a lower activation energy for 1,5-substituted product generation, as explained by the distortion-interaction analysis. Furthermore, the FMO analysis revealed that the binding of Nmethylimidazole to zinc increased the energy of the HOMO of ethyl(phenylethynyl)zinc, which increased its reactivity.

The LnAAC reactions

Recently, a seminal example of rare earth-metal-catalyzed AAC reaction with terminal alkynes leading to 1,5-disubstituted 1,2,3triazoles was described by Zhou's group [110]. The authors chose [Sm{N(SiMe 3 ) 2 } 3 ] as the catalyst after compared examination of the rare-earth metal catalysts [Ln{N(SiMe 3 ) 2 } 3 ], Ln = Sm, Nd, Y, Gd. Optimization of the reaction conditions showed that the presence of 10 mol% n-BuNH 2 improved the yield (Fig. 20a). By comparison, they suggested that the involvement of an acetylide intermediate complex was essential for the efficiency and selectivity. The proposed mechanism is shown in Fig. 20b. First activation of the C H bond of the terminal alkyne produced the Ln acetylide A and HN(SiMe 3 ) 2 . Then 1,1-insertion of the azide in the Ln C bond of A gave the species C and D, and the anti-nucleophilic attack of the nitrogen atom to the -coordinated alkyne led to the triazolate E. Then, the protonation of E with another alkyne molecule afforded 17 and regenerated A (path a). In an alternative pathway, path b was suggested based on the presence of amine additives that were favorable to the cycloaddition.

We have computationally explored this proposed mechanism by DFT calculations considering the complex [Y{N(SiH 3 ) 2 } 3 ] (YL 3 ) as the simplified precatalyst, acetylene and hydrogen azide [27b]. The induction part of the mechanism (path a in the left side of Fig. 20b) that corresponds to the formation of the acetylide intermediate and a protonated ligand is computed to proceed with a rather low free energy barrier (7.0 kcal/mol). The computed B to E transit of Fig. 20b was a single step process and the rate-determining one, with a transition state that is 13.7 kcal/mol above B (Fig. 21). These results confirmed the proposed mechanism of Zhou's group (path a in Fig. 20b), although the pathway from B to E was computed to be a single step. Likewise, Li's group also recently computationally investigated the same catalytic process that was performed considering the pre-catalyst model [SmL 2 S(CCPh)] (L = acetylide) and benzyl azide [111]. In their case, the observed 1,5 isomer was produced from the formation of an intermediate that resulted from the azide coordination on [SmL 2 S(CCPh)] through its substituted nitrogen atom. This computed result was different from ours, indicating that only the 1,4-trz isomer was formed in this pathway though a similar mechanism, but with a higher energy barrier.

Recent trends

Following the basic features that characterize the MAAC reactions including the state of the art in the mechanistic understanding with various metals, recent trends essentially in CuAAC and RuAAC have appeared that are gathered in this section.

CuAAC

N-heterocyclic carbenes (NHCs) have become an increasingly used class of "L" ligands in organometallic chemistry and click catalysis [112]. Following the seminal work by Nolan's group [33], the Cu(I) complexes of NHC ligands were continuously very efficient catalysts for the click cycloaddition reaction between azides and alkynes [38,113]. Lal et al. compared the catalytic activity of NHC and phosphine complexes for the CuAAC formation of 5-iodo-1,2,3triazoles (Fig. 22). The experimental/computational-DFT results suggested that iodoalkynes might be prone to dehalogenation under copper catalysis conditions. Two distinct mechanistic pathways that proceed through a copper(III) metallacycle or by direct -activation of the starting iodoalkyne are likely to be competitive with these catalysts [112a]. Other carbene ligands that were recently used with success in catalysis of click reactions include abnormal N-heterocyclic carbenes (aNHCs) [55,114], mesoionic carbenes (MIC) and ring-expanded carbenes (RE-NHCs) [115]. With copper(I) complexes of triazolylidene ligands (Fig. 23a) [116] the halide-free complexes [Cu(aNHC)][BF 4 ], 20-23, are more efficient than the halide-containing complexes 18 and 19 in catalyzing CuAAC reactions. The complex [CuCl(aNHC)] (Fig. 23b) catalyzed CuAAC reactions in excellent yield at r.t. within short reaction time under solvent-free conditions [117]. With the complex [Cu(I)(MIC)], addition of a phenanthroline derivative generated 19 Fig. 21. DFT free energy profile (in kcal/mol) computed for the mechanism of the formation of 1,5-triazole catalyzed by a rare-earth complex reported in Ref. [110] (R 1 = R 2 = H; relative free energy values). a highly active catalyst that surpassed the performances of a "normal" NHC complex, which was taken into account by the combination of a greater electron-donating character of the carbene ligand and a less crowded environment of the catalytic center [118]. Beside the NHC ligands, Cu(I) complexes bearing one or two ␣-diimine ligands [119], hybrid nitrogen-sulfur ligand-supported Cu(I)/(II) complexes [120] were also highly efficient. Other recently Reproduced with permission from Refs. [116] and [117], respectively. Copyright 2013, WILEY-VCH.

reported useful systems include Cu(II) complexes supported by mixed NN, NO, and NS 1,2,3-triazole based ligands utilized together with sodium ascorbate [121], Cu(I) complexes with pyridyl and thioether hybridized 1,2,3-triazole ligands [122], Cu(I) complexes containing sulfur-based ligand [123], Cu(I) complexes with new chiral phosphine ligand [124], dinuclear Cu(I) complex (Cu 2 (pip) 2 ) with (2-picolyliminomethyl)pyrrole anion ligand [125], and binuclear Cu(I) complex of (N ′ 1E,N ′ 2E)-N ′ 1,N ′ 2-bis(phenyl(pyridin-2-yl)methylene)oxalohydrazide ligand [126]. On the other hand, Cu(II) species without deliberate addition of a reducing agent for CuAAC reactions have also been investigated. The mechanistic studies indicated that the real catalytic Cu(I) species were generated in a short induction period via reducing Cu(II) salts by alcoholic solvents [127], sodium azide [46,128], or thiobenzanilide [129] especially in the three-component 1,3-dipolar cycloaddition for 1,4-disubstituted 1,2,3-triazoles synthesis. For instance, the recently reported 2-pyrrolecarbaldiminato-Cu(II) complexes efficiently catalyzed three-component 1,3-dipolar cycloaddition reaction of benzyl halides and sodium azide with terminal alkynes in water at r.t., leading to the synthesis of several regioselective 1,4-disubstituted 1,2,3-triazoles in 55-97% yield [130]. On the other hand, the direct use of Cu(I) complexes to catalyze threecomponent reactions of N-tosylhydrazones, terminal alkynes and azides to efficiently synthesize 1,4,5-trisubstituted 1,2,3-triazoles with good to excellent yield has also recently been explored by Wang's group [131].

From the above examples and many others, the catalysts for CuAAC reactions are usually homogeneous catalysts. Although they are often very efficient, their preparation often is tedious and/or expensive. Together with the difficulties in handling and recycling the catalysts, the applications toward the click reactions using homogeneous catalysts are somehow limited. To solve these problems, considerable interest and efforts have been devoted to develop suitable supports, especially in the field of the heterogenization of homogeneous catalysts. For example, Varma's group reported a recyclable heterogeneous copper catalyst on chitosan for CuAAC reactions in water [132]. The chitosan-supported catalyst was simply obtained by stirring an aqueous suspension of chitosan in water with copper sulfate. The catalyst was very efficient in catalyzing CuAAC in water at r.t. (Fig. 24); it was recycled and reused at least 5 times without losing its activity and changing morphology. Pourjavadi and coworkers recently reported the immobilization of copper ions (CuSO 4 ) in a graphene oxide/poly(vinyl imidazole) nanocomposite (GO/Pim/Cu) as highly efficient, robust and recyclable catalysts for one-pot three-component cycloadditions in water in the presence of NaAsc as the reductant [133]. Moreover, they also successfully reduced the amount of catalysts to 0.002% mol with 93% isolated yield of product in water at 50 • C for 20 h.

Immobilizing Cu(II) on silica-type materials, such as SBA-15, to build up heterogeneous catalysts, has also been achieved [134]. For example, Roy's group recently reported Cu(II)-anchored functionalized mesoporous SBA-15 for one-pot CuAAC reaction [134a]. In a typical synthesis procedure shown in Fig. 25, 2pyridine-carboxaldehyde was added to a mixture of 3-amino propyl-functionalized SBA-15 in super dry ethanol. The reaction mixture was then stirred at 60 • C for 24 h to yield SBA-15 supported imine material. Then, reaction of Cu(OAc) 2 with SBA-15 yielded the catalyst Cu@PyIm-SBA-15. This catalyst in low amount (0.1 Cu mol%), showed a good activity and reusability for the one-pot click reaction between azides formed in situ from the corresponding amines and acetylenes in water at 0 • C to r.t., providing a wide variety of 1,4-disubstituted 1,2,3-triazoles. The electron paramagnetic resonance (EPR) spectrum of the fresh and used catalyst suggested that copper remained in +2 oxidation state throughout the reaction which was taken into account by Cu 2+ as catalyst, though such evidence does not prove the absence of active Cu(I) species [135]. Nasr-Esfahani reported copper immobilization on nanosilica triazine dendrimer (Cu(II)-TD@nSiO 2 , Fig. 26a), and excellent yield via a one-pot three-component reaction of alkynes and sodium azide with organic halides or ␣-bromo ketones at r.t. (Fig. 26b). Sodium ascorbate was then needed to reduce Cu(II) to Cu(I) [136], and the synthesis of 1,4-disubstituted 1,2,3-triazoles and bis-and tris-triazoles proceeded in a single-step operation. Cu(I) catalytic species were also reported upon immobilization onto solid supports for CuAAC reactions, such as silica cuprous sulfate (CDSCS) doped with Cu(I) [137], Cu(I) on modified poly(styreneco-maleic anhydride) [138], Cu(I) onto triazole functionalized Fe 3 O 4 [139] and CuBr on graphene oxide/Fe 3 O 4 [140].

Cu 2 O, another Cu(I) source, is also used for the CuAAC reactions, though in some cases a stabilizer such as PVP was used to enable the formation of the well-defined and small copper(I) oxide [141]. Bai and Chen's group demonstrated the safe and high efficient synthesis of triazole drugs by using a Cu 2 O-NP catalyst in aqueous/organic solvents (CH 3 CN and H 2 O) for the key AAC stage (Fig. 27) [142]. In their study, Cu 2 O-NP was more efficient than CuSO 4 /NaAsc, which was explained by the fact that the Cu 2 O-NP catalyst was dispensed in both organic solvent and water, while the CuSO 4 /NaAsc system required higher ratio of water. The in situ generated Cu 2 O together with HOAc exhibited better catalytic efficiency than isolated Cu 2 O combined with HOAc [143]. The Cu(II) species in Cu(OAc) 2 •H 2 O was also reduced to Cu(I) by NH 2 NH 2 •H 2 O that could in situ generate Cu 2 O-NPs and HOAc to efficiently catalyze CuAAC reactions in water at r.t. with relatively short reaction times. However, drawbacks are obvious, because of the unrecoverable and unreusable properties of small molecular organic acids. In order to overcome these problems, the authors latter on combined Cu 2 O and carboxymethylpullulan (CMP) for high-yield CuAAC reactions in water with a relatively short reaction times, and CMP still remained in water enabling easy recoverability and reusability [144]. Very recently, Cu 2 O supported on graphene nanosheet [145] served as recyclable and reusable heterogeneous catalyst with excellent catalytic activity for CuAAC. More importantly, an excellent performance was also obtained for bulk CuAAC reactions via melt-rheology with trivalent azide-and alkyne-functionalized polyisobutylenes (PIB) at r.t. (Fig. 28), which was useful for designing self-healing materials. Additionally, special rhombic dodecahedra Cu 2 O bounded by the {110} facets was also a promising heterogeneous catalyst for multicomponent AAC reactions [146].

Copper nanoparticles (CuNPs) have attracted interest for the CuAAC reactions due to their large surface area, tunable morphology and sustainable catalytic activities on the use of CuNPs to catalyze the CuAAC reaction by Fokin et al. [31], efforts have been devoted to design highly-efficient and lowcost heterogeneous CuNPs catalysts for this reaction. However, in most cases, strategies had to be developed in order to prevent CuNPs agglomeration [147], enabling the stability of small CuNPs and high activity toward CuAAC. For example, agarose was a cheap and degradable polysaccharide for the stabilization of active CuNP (CuNPs@agarose) in the size range of 4-8 nm in water under Reproduced with permission from Ref. [153]. Copyright 2013, American Chemical Society.

low catalyst loading and mild reaction conditions [148]. The 3aminopropylsilica support was able to stabilize smaller CuNPs with the size in the range of 1-4.5 nm, leading to very high catalytic activity (productivity up to 1689 mol/mol) in continuous-flow click reaction between phenyl acetylene and benzyl azide [149]. A more recent case showed fluorescent aggregates of hexarylbenzene derivatives serving both as reactors and stabilizers for the preparation of 9-17 nm-sized CuNPs with efficient catalysis of CuAAC reactions in excellent yield under solvent-free conditions [150].

On the other hand, Sureshan's group also successfully developed a simple methodology to generate naked CuNPs or their clusters as catalysts (CuSO 4 •5H 2 O + N 2 H 4 •H 2 O) that did not require stabilizers, solid support, or special conditions for solvent-free CuAAC reactions at r.t. (Fig. 29) [151]. Interestingly, Cravotto's group successfully adopted ball-mill-based mechanochemical activation of metallic copper powder that facilitated solvent-free CuAAC reactions. This new, efficient, facile and eco-friendly procedure has afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yield and purities [152].

Alonso and Yus et al. have also investigated the use of CuNPs for multicomponent CuAAC reactions [80]. They showed that the nanostructured CuNPs supported on active carbon (CuNPs/C) catalyst displayed much higher catalytic activity than commercial bulk copper catalysts in the one-pot synthesis of 1,2,3-triazoles from inactivated alkenes. Their sequence involved two click steps including first the azidosulfenylation of the olefin, then the reaction of the in situ generated organic azide with the terminal alkyne (Fig. 30b) [153]. Other recently reported nanostructured Cu catalysts for three-component CuAAC reactions included CuNPs [154], heterogeneous porous Cu(0) [155], and CuNPs on silica coated maghemite nanoparticles (CuNPs/mag silica) [156].

Since Lipshutz's seminal study involving nickel oxide NPs in the CuAAC reaction [157], essentially Cu-M bimetallic alloys (M = metal or its oxides NPs, mainly Fe and Ni) have been explored in the AAC reaction. Among these various bimetallic alloyed nanostructures for AAC, Cu is known for its catalytic efficiency, while M is known for its magnetic nature or other catalytic efficiencies except for AAC. In the case of the CuFe system, although Nageswar's group showed the successful multicomponent synthesis of 1,4-disubstituted 1,2,3triazoles in water at 70 • C catalyzed by magnetically separable CuFe 2 O 4 [158], low efficiency of CuFe 2 O 4 NP-catalyzed benzyl azide and phenylacetylene cycloaddition in water at r.t. was also observed [159]. To alleviate this limitation, they then synthesized bimetallic CuFe NPs by using presynthesized FeNP-reducted CuSO 4 .

Here, the presence of FeNPs served both as the electron source to reduce Cu(II) into Cu(I) and the support for Cu(I) species to prevent their liberation as soluble ions, enabling a heterogeneous mechanism for the CuAAC reaction. Likewise, Fulop's group also recently showed that iron powder was a readily available copper scavenger for continuous-flow CuAAC [160]. By contrast, in the case of the CuNi bimetallic alloy nanostructures, heterogeneous Cu-Ni/C catalysts have independently been reported by Lipshutz's [157] and Tang's group [161]. In the former case, Cu-Ni/C mediated both group 10 and group 11 cross-couplings [157], whereas in the latter case, transformation of waste polymer materials into valuable metal/carbon heterogeneous composites was highlighted. In this approach, the Cu/Ni molar ratios (initial catalytic substances were Ni 2 O 3 and CuCl) played a crucial role in the formation of the microstructures and for the catalytic functions. Although Cu-Ni/C-0.5 was used to catalyze a CuAAC reaction with high yield (97%), the reaction time was longer compared to those of previous reports [157,162], which was attributed to the amorphous nature of carbon covering the Cu particles in Cu-Ni/C-0.5, leading to insufficient catalysis [161]. On the other hand, Mandal's group also showed that chain-like bimetallic magnetic CuNi nanoalloy in the presence of polymers (PVP or PEG) is a stabilizing/structure-directing agent for CuAAC reactions with good to excellent yield in water and in DMF at r.t. XPS and zeta potential analysis confirmed that Cu(I) on the alloyed NPs surface was responsible for the catalytic activity, while the magnetic reusability was attributed to Ni [163]. This novel unsupported Cu based nanocatalyst was highlighted for its advantages of both homogeneous and heterogeneous catalysis while avoiding their drawbacks, and it was called pseudo-homogeneous catalyst. Moreover, a new bimetallic catalyst derived from nickel and copper supported on magnetite was a good catalyst for the multicomponent reaction of terminal alkynes, sodium azide, and benzyl bromide derivatives, because of the positive and synergetic effect of the metallic species [164].

The use of microwaves was a valuable assistance in CuAAC reactions upon considerably shortening reaction times, and it improved yield [20,127c,165]. Perics's group reported the synthesis of tris(triazolyl)methane ligands [166] with CuCl for CuAAC of benzyl azide with representative alkynes. For instance with tris(aryltriazolyl)methanol-CuCl (see the ligands in Fig. 31), both [167], recoverable and recyclable Cu/SiO 2 composite for eco-friendly multicomponent synthesis of 1,2,3-triazoles [168], "copper-incharcoal" catalyzed triazole click reactions [169], palladium and copper-supported on charcoal as heterogeneous multi-task catalysts for sequential Sonogashira-click and click-Heck reactions [170], Cu/porous glass catalyst for CuAAC in water [165c], CuNPs supported on nano-Fe 3 O 4 -glutathione (Cu/nano-FGT) for one-pot multicomponent synthesis of 1,2,3-triazoles [171], and Fe 3 O 4supported CuBr catalysts for one-pot and scale-up synthesis of 1,2,3-triazoles (Fig. 32) [172]. When CuNPs are used, it is indeed assumed that surface oxidation of Cu(0) to catalytically active Cu(I) species occurs upon MW irradiation.

Concerning the CuAAC reaction using the conventional Sharpless-Fokin catalyst CuSO 4 •5H 2 O + Na Asc. for multiple applications, the shortcoming as already mentioned above is its large quantity, together with the toxicity of copper, limiting the potential for large applications in electronics, biomedicine and biological chemistry. Thus, new Cu(I) catalysts are on the "top-wanted" list. Our group recently developed the catalyst [Cu(hexabenzyl)tren][Br] that was easily synthesized, toluene soluble, efficient, easy to separate from products and recyclable [35]. In this approach, reactions achieved TONs of the order of 10 4 reached upon recharging substrates with only 0.1 mol% amount of catalyst. The latter was active for "click" reactions between azides and alkynes in toluene or water, and the system recharged at least 10 times. A key advantage of this catalyst [35] compared to Sharpless catalyst is the tremendous ligand acceleration of the reaction.

Other recent well-defined supramolecular catalytic approaches for the CuAAC reactions such as polymer-supported catalysts of Cu(I)-poly(styrene-co-maleimide) (CuI-SMI) for the one-pot threecomponent click synthesis of 1,4-disubstituted-1H-1,2,3-triazoles [138], polymer-anchored PS-C22-CuI for three-component synthesis of 1,4-disubstituted 1,2,3-triazoles under aerobic conditions in water [173], polymer-supported catalyst Amberlyst A-21-CuI for the synthesis of 1,4-disubstituted-1H-1,2,3-triazoles in CH 2 Cl 2 at r.t. [174], Cu(I)-incorporated microporous Schiff base network polymer for CuAAC in MeCN at r.t. [175], supramolecular material of polymer supported Cu(I) catalyst, (Cu(I)-poly(2-aminobenzoic acid), Cu(I)-pABA), showed excellent yield toward AAC reactions at r.t. in aqueous media [176]. The combined use of two polymer supported reagents (polystyrene-1,5,7-triazabicyclo[4,4,0]dec-5ene/Cu and polystyrene-2-iodoxybenzamide) enabled the reliable CuAAC in the presence of an oxidant agent [177], CuI onto dimethylamino-grafted cross-linked polystyrene (CuI@A-21) for azide-alkyne click polymerization [178], and metal-organic framework (Cu-MOF, Cu(PTZ)(NSA) 0.5 •H 2 O) for the solvent-free CuAAC [179], were also successfully achieved.

In addition, some of the abnormal 1,2,3-triazoles, for example N-carbamoyl 1,2,3-triazoles [180a], and 1,4,5-trisubstituted 5-dialkylamino-1,2,3-triazole [180b] were also successfully synthesized to fill the gap.

Interestingly, the Rennes-Valparaiso groups discovered that organometallic Schiff-base copper complexes were excellent precatalysts for the CuAAC reactions, including with regenerated polymethylmethacrylate supports [181].

RuAAC

Recent applications of Cp*RuCl-based catalysts included the synthesis of 4-haloisoxazoles and 5-halotriazoles [81], thiolactoside glycoclusters [83], one-step synthesis of triazoles [84], palladium-based metallocene complexes [85], 1,2,3-triazole peptides [86], 5-TTF-1,2,3-triazoles [87], 1,5-substitued 1,2,3-triazole amino acids [182], 5-amino-1,2,3-triazole-4-carboxylic acid [183a], and fluorinated 1,4,5-substituted 1,2,3-triazoles [183b].

RuAAC reactions catalyzed by Ru(II) complexes and RuNPs were also reported. In the former case, our group reported the simple and efficient synthesis of magnetically recyclable magnetic NP-supported pentamethylcyclopentadienyl Ru(II) catalyst (see Fig. 33a) for RuAAC reactions to yield the fully selective construction of 1,5-disubstituted 1,2,3-triazoles [184]. The catalyst provided excellent yield and almost 100% selectivity for the target product and was reused five times by simple magnetic separation with only a minimum decrease in catalytic activity and selectivity, (Fig. 33b) and little change in the morphology and size of the NPs.

A +3 metal oxidation state of polymer supported ruthenium complex was first demonstrated by Molla et al. who reported the synthesis of 1,4-disubstituted 1,2,3-triazoles in water with excellent yield via multicomponent coupling in aqueous medium at r.t [185]. On the other hand, Lee's group synthesized the RuNP catalyst using the co-precipitation method. The RuNP catalyst exhibited good results in terms of reactivity in the RuAAC reactions, but the size effect strongly influenced the catalytic activity of these RuNP catalysts, because the size of the catalyst was sensitive to parameters such as the pH of the medium and the type and concentration of the surfactant [186].

MW-assistance promoted RuAAC reactions [82,84,87], as recently exemplified by Johansson et al. who reported one-pot RuAAC reactions to synthesize 1,5-disubstituted 1H-1,2,3-triazoles involving two steps under microwave heating (Fig. 34). First of all, the organic azide was formed in situ by treating the primary alkyl halide with sodium azide in DMA under microwave heating, then the catalyst [RuClCp*(PPh 3 ) 2 ] was added, and a second microwave irradiation was applied to yield the cycloaddition product [187].

Applications of the CuAAC "click" reactions

The CuAAC reaction is considered as the most robust and straightforward synthetic procedure for various organic syntheses [188], especially in building novel structures, including natural products modifications [189], the synthesis of porphyrin based derivatives [190], the iterative click construction of dendrimers that are terminated with various functional groups [191], and polymers [192]. In the case of the dendrimer the "click" synthesis of a water soluble dendrimer that contained 9 intradendritic triazole rings and terminated by 27 triethylene glycol (TEG) termini was reported and used as nanoparticle stabilizer and catalyst template. This dendrimer has recently been employed as an amphiphilic micellar nanoreactor, stabilizer and activator for part-per-million Cu(I) catalyst of "click" chemistry in water under ambient conditions, due to its coordination and encapsulation abilities of Cu(I)-ions and hydrophobic Cu(I)-catalysts, respectively [27a]. The "click" synthesis of polycondensation metallopolymers containing redoxrobust bis(ethynyl)biferrocene (biFc) and di(azido) poly(ethylene glycol) was also achieved [193]. This polymer showed intriguing properties; the biFc unit provided a class-II mixed-valence polyelectrolyte and electrochrome properties, while the presence of PEG in the polymer improved the water solubility and biocompatibility. The triazole linkers between biFc and PEG units facilitated redox sensing of transition-metal cations. Moreover, this easy available polymer was an excellent template for the stabilization of catalytically active AuNPs and PdNPs for 4-nitrophenol reduction and Suzuki-Miyaura reaction, respectively.

The easy accessible click approach of various material constructions has a great impact in materials science [194a,b]. The excellent reviews on click chemistry in materials science by Bowman's group [194a] and Diaz [194b] cover this area. Veige's click functionalization of inorganic complexes (inorganic click) by reaction of PPh 3 AuN 3 with alkynyl-or p-substituted alkynyl gold complexes led to bi-and polymetallic triazoles [194c-g], and the functionalization of gold nanoparticles has also proved to be an effective method for the construction of novel nanostructures [195]. The functionalization of carbon-based nanomaterials has long attracted the interest of researchers. For example, CuAAC functionalizations of C 60 derivatives have been achieved [196] and improved their solubility. Recent examples include the preparation of fullerene sugar balls [197], C 60 -containing polymers [198], viral nanoparticle (VNP)-C 60 conjugates [199], supramolecular interactions between molecular tweezers and macrocycles, functionalization of C 70 fullerenes [200], and biotinylation of fullerene vesicle via CuAAC and conjugation with avidin [201]. Functionalized graphene and partially reduced graphene oxide (rGO) functionalized on the surface provide possibilities for improving the electrical strength recovery and utilization in devices. Functionalized rGO surface covalently immobilized with metal nanoparticles such as AuNPs and AgNPs, through the organic linkers is a good tool for achieving controllable transport in memory devices [202] and electron transfer in photocatalysis [203]. Click formation of 1,2,3-triazoles on the surface of rGO combined with localized surface plasmon resonance (LSPR) effect of the AuNPs allowed the observation of a fivefold photocurrent enhancement for triazole linkers. This showed that the triazoles linker between rGO and AuNPs were very efficient for charge separation and electron transfer [203].

In the field of biology, click chemistry has also been extensively used with various successful biological, chemical and medicinal applications [204] including nucleic acid ligation [205], bioconjugation for protein modification [206], drug design [207], gel syntheses for biomedical applications [208], chemical modification of biological molecules [209], and biomolecular labeling [210] activity-based protein profiling (ABPP) [211].

Conclusions and outlook

The MAAC reactions are of considerable use in synthesis with applications in materials science and biomedicine, and they remain by far the most prominent example of "click" chemistry. Therefore considerable research has been devoted to extend the variety of metal catalysts and to mechanistically understand the different MAAC reactions with the help of theoretical calculations, characterizations of intermediates and optimization of reaction parameters. In this field as in many others the theoretical calculation and experimental progress are intimately connected in order to improve the reaction efficiency, simplify procedures and apply them to industry in particular by decreasing catalytic amounts. Thus both mechanistic advances and recent trends of AAC "click chemistry" have been reviewed here. The multiple new advances are inspiring for theoretical chemists to rationalize the mechanisms of new routes. In turn, the theoretical advances guide and lead chemists to imagine new reaction improvements.

The CuAAC reaction remains the most currently used MAAC reaction, and the review has highlighted a multitude of reported improvements including the use of excellent Cu(I) ligands, copper metal and CuNPs in various forms to make this click reaction more practical and more easily applicable. The very practical initial Sharpless-Fokin catalyst CuSO 4 + NaAsc remains most often used, and with the use of optimized ligands researches have led to considerable decrease of the catalytic amounts down to the ppm permitting industrial applications. Some theoretical calculations have converged to the identification of a bimetallic , 25 intermediate in a bimetallic mechanism. On the other hand, studies showed that in the presence of very low amounts of catalyst a monometallic mechanism was occurring in catalytically efficient Cu(I)-centered dendrimers with positive dendritic effect for the smaller substrates and in extraordinarily efficient dendrimermediated Cu(I) catalysis. The complete change of regioselectivity provided by the RuAAC reaction discovered by Fokin's group has been perfectly rationalized mechanistically, but Nolan's introduction of the NHC ligands in the RuAAC reactions showed alternative results and mechanistic features. Many more metals are active in MAAC reactions and some of them including lanthanides have been mechanistically rationalized based on theoretical calculations. Indeed, the quality of modern theoretical calculations with DFT methods now allows confident mechanistic approaches with excellent determination of reaction energetics, for both thermodynamic and kinetic sides.

In conclusion calculations and experimental research have brought MAAC at the forefront of "green chemistry" with mild, environmentally benign and useful synthetic methods that are now applicable to industry. Further work including computational and experimental research is required, however, to push MAAC toward multicomponent "one-pot" syntheses [212] for industrial production and to design multi-task catalysts based on bimetallic or multi-metallic systems for tandem reactions.

chemistry, [2-11] polymer science and materials science. [12-21] Among the various "click" reactions responding to the requirements of this concept, the most generally used one is the copper(I)-catalyzed reaction between terminal alkynes and azides (CuAAC) selectively yielding 1,4-disubstituted 1,2,3-triazoles, that was reported independently by the Sharpless-Fokin [22] and the Meldal groups in 2002. [ 23,24] This reaction is the catalyzed version of the 1,3 dipolar cycloaddition, known in the former decades as the Huisgen reaction that had already been first disclosed in the XIXth century. [25] The advantages of the Cu(I) catalyzed "click" reaction are that:

(i)
it is regioselective, whereas the non-catalyzed Huisgen reaction lacks regioselectivity, producing both the 1,4-and 1,5-disubstituted isomers;

(ii) it proceeds at milder temperature than the non-catalyzed reaction;

(iii) it fulfills the requirements of "green chemistry" in so far as it can occur in aqueous or alcoholic medium;

(iv) the catalyst reported by Sharpless and Fokin is simple and inexpensive; it consists in CuSO 4 •5H 2 O and sodium ascorbate.

The only drawback is the need of large quantities of this catalyst mixture that is slow.

Indeed, various nitrogen ligands accelerate the Cu(I) catalysis of the "click" reaction and allow using 1% or a few % Cu (I) catalyst. [20,26] For the Cu(I) catalyzed reaction, a variety of mechanisms involving Cu(I)-aryl intermediates have been proposed in which the key-step species contains either mononuclear [27] or binuclear copper species. [28-35] With pentamethylcyclopentadienyl-ruthenium catalysts, however, the Fokin group showed that the other isomer, i.e. 1,5-disubstituted triazole is regioselectively formed in the RuAAC reaction even with disubstituted alkynes according to a different mechanism. [36] Ruthenium catalysis is versatile, because other ruthenium catalysts reacted with terminal alkynes via a key ruthenium-acetylide species to yield the 1,4-disubstituted triazoles. [37] Ag(I) catalysts of the AAC reaction without copper at room-temperature (r.t.) [38] indicated that silver acetylide intermediate activated the formation of an acetylideazide species toward cyclization. [39] An ""abnormal"" NHC complex, Ag(I)-aNHC, catalyzed the ACC reactions. [40] It showed that silver chloride by itself catalyzed the cycloaddition of various alkynes and azides in good yield, however with side reactions. Moreover, in the case of AgNP/graphene oxide (Ag/GO) catalyst, multi-component reactions and one-pot click reaction were efficiently catalyzed; the catalysts were very stable and showed no silver leaching or aggregation and were reused at least 5 times without loss of catalytic activity. [41] For the AuAAC, X-ray photoelectron spectroscopy suggested that significant degradation of the azide upon adsorption occurred on the surface, though the reaction proceeded readily; especially the intact reactants were available on the surface. [42] On the other hand, the mechanism of heterogeneous reusable Au/TiO 2 nanostructure to efficiently catalyze the AAC reaction involves : (i) a gold atom (I) reduced the electron density on the alkyne, enabling facile nucleophilic attack by the azide; (ii) a six member intermediate II, then intermediate III formed (iii) gold was removed to afford 1,4-disubstituted 1,2,3-triazoles and complete the reaction cycle. [43] While in the case of iridium-catalyzed intermolecular AAC (IrAAC), the dimeric iridium complex [Ir(cod)OMe] 2 catalyzed the direct formation of new 1,4,5-trisubstituted triazoles. [44] The electronic features of the alkyne component strongly affected the reaction yield. Ding et al. compared various Ir complexes in the IrAAC of electron-rich internal alkynes and showed that the increase of steric hindrance on the alkyne did not affect the reaction efficiency, but an electronic effect was crucial. [45] Lin, Jia and coworkers [46] then rationalized through DFT calculations the differences in the regioselectivities of addition of thioalkynes and bromoalkynes to azides.

Raney Ni, without additional reducing agent, efficiently catalyzed acetylene azide cycloaddition reactions to form 1,2,3-triazoles with excellent yield. To explore the NiAAC reaction pathway, deuteration experiments were conducted in the presence of Ni(0) indicating that, unlike the copper-acetylide formation in CuAAC, the cycloaddition went through a metallocycle. [47] For the ZnAAC reactions, heterogeneous zinc-on-charcoal (Zn/C) catalyzed the cycloaddition of aryl/aliphatic azides and aryl alkynes (including internal alkynes) in DMF at 50 °C without exclusion of air (63%-94% yield) [48] When ZnNPs were alloyed with CuNPs to form the catalysts for multicomponent 1,2,3-triazole synthesis/triazole alkynylation, the presence of Zn resisted the oxidation of Cu by sacrificial formation of ZnO that played a role in controlling the formation of alkynylated triazoles. [48] On the other hand, DFT calculations towards the mechanism and regioselectivity research of this ZnEt 2 catalyzed regioselective formation of 1,5-substituted 1,2,3-triazoles at r.t.; [49] ethynylzinc complexes bearing alkyl substituents showed a reactivity analogous to that of ethyl(phenylethynyl)zinc and a lower regioselectivity. Higher regioselectivity was due to a lower distortion energy in the transition state and led to a lower activation energy for 1,5-disubstituted product generation.

Rare earth-metal-catalyzed AAC reaction with terminal alkynes leading to 1,5-disubstituted 1,2,3-triazoles was described by Zhou"s group. [50] The authors chose [Sm{N(SiMe 3 ) 2 } 3 ] as the catalyst after compared examination of the rare-earth metal catalysts [Ln{N(SiMe 3 ) 2 } 3 ], Ln = Sm, Nd, Y, Gd. Optimization of the reaction conditions showed that the presence of 10 mol% n-BuNH 2 improved the yield. By comparison, they suggested that the involvement of an acetylide intermediate complex was essential for the efficiency and selectivity.

On the other hand, following the basic features that characterize the MAAC reactions including the state of the art in the mechanistic understanding with various metals, recent trends essentially in CuAAC and RuAAC have appeared that are gathered. The recent trends in CuAAC involve:

(i)
The design of "L" ligands, well-defined supramolecular catalytic approaches in organometallic chemistry and click catalysis;

(ii) The direct use of Cu(I) complexes to catalyze three-component reactions;

(iii) Recyclable heterogeneous copper catalyst for CuAAC reactions, including the use of Cu 2 O and copper nanoparticles (CuNPs) for the CuAAC reactions.

(iv) Abnormal 1,2,3-triazoles synthesis.

Moreover, recent developments of the CuAAC reaction are also reviewed in the fields of organic syntheses, materials science, and biological, chemical and medicinal applications.

The recent trends in RuAAC involve:

(i)
The applications of Cp*RuCl-based catalysts to the synthesis of 1,2,3-triazoles;

(ii) The design of novel Ru(II) complexes and RuNPs catalyzed RuAAC reactions;

(iii) Physical methods promoted RuAAC reactions.

From the above short summary, considerable research has been devoted to extend the variety of metal catalysts and to mechanistically understand the different MAAC reactions with the help of theoretical calculations, characterizations of intermediates and optimization of reaction parameters. In this field as in many others the theoretical calculations and experimental progress are intimately connected in order to improve the reaction efficiency, simplify procedures and apply them to industry in particular by decreasing catalytic amounts. Thus both mechanistic advances and recent trends of AAC "click chemistry" have been reviewed. The multiple new advances are inspiring for theoretical chemists to rationalize the mechanisms of new routes. In turn, the theoretical advances guide and lead chemists to imagine new reaction improvements.

In conclusion, calculations and experimental research have brought MAAC at the forefront of "green chemistry" with mild, environmentally benign and useful synthetic methods that are now applicable to industry. Further work including computational and experimental research is required, however, to push MAAC towards multicomponent "one-pot" syntheses [51] for industrial production and to design multi-task catalysts based on bimetallic or multi-metallic systems for tandem reactions.

Introduction

Our group has long been engaged in the use of copper-catalyzed alkyne-azide Huisgen-type cycloaddition (CuAAC, "click" reactions) yielding weak 1,4-disubstituted 1,2,3-triazoles (trz) ligands that mildly stabilize various transition metal nanoparticles (trz-NPs) that are very efficient catalysts in water. Amphiphilic dendrimers as nanoreactors have been exploited for catalysis in water with as little as parts per million (ppm) amounts of metal amounts from TMNP catalysts. [1] The synthesis and use in catalysis of amphiphilic dendrimers as nanoreactors represents a very productive sophistication, but it is time-consuming. On the other hand, trz ligands with PEG tails were recently shown to stabilize AuNPs that catalyze 4-nitrophenol reduction in water with excellent rates. [2] We then In the third part, we report that the CuAAC reaction using the conventional Sharpless-Fokin catalyst that consists of CuSO 4 + Na ascorbate, the most well-known and used "click" reaction, is considerably accelerated by the addition of a tris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand in water under ambient conditions. Only parts-per-million Cu I were necessary to reach quantitative yields with TON up to 86000 and TOF 3600 h -1 . The ligand was fully recycled, and the catalyst reused at least 6 times without decomposition. Large-scale syntheses were also successfully achieved with 93 % yield. The catalyst was applied to the efficient synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties.

Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions

Changlong Wang,Roberto Ciganda, Lionel Salmon, Danijela Gregurec,J oseba Irigoyen, Sergio Moya, Jaime Ruiz, and Didier Astruc* Since the seminal discoveries by Haruta [1] and Hutchings, [2] catalysis of chemical reactions by transition metal nanoparticles (TMNPs) has attracted considerable interest owing to its efficiency, greenness,c onvenient use,a nd improved understanding of reaction mechanisms. [3-9] Thes upport and medium have been shown to play an essential role in TMNP catalysis,but relatively little attention has been paid to TMNP surface ligand design. Yetb oth TMNP formation in micelles or inverted micelles and catalysis therein are also strongly dependent on the stereoelectronic parameters of the stabilizing agents. [10-13] Catalysis in water offers great advantages in terms of green chemistry,a nd has recently been actively investigated. [14-21] Fori nstance,a mphiphilic dendrimers are unimolecular micelles, [18-20] and this property has recently been exploited for catalysis in water with little as parts per million (ppm) amounts of molecular or TMNP catalysts. [21] The synthesis and use in catalysis of amphiphilic dendrimers as nanoreactors represents avery productive sophistication, but it is time-consuming,a nd one can conceptualize ar elated approach using simpler amphiphilic ligands.

Toward this goal, we suggest the design of weak, but multidentate bulky ligands that offer both easy displacement from TMNP surface by substrates for catalysis and sufficient TMNP stabilization. As ar esult, we report the amphiphilic tripodal ligand tris(1,2,3-triazolyl)-polyethylene glycol (tristrz-PEG), 2,t hat led to the synthesis of very small TMNPs with various transition metals (Fe, Co,Ni, Cu, Ru, Ag, Pt, Pd, and Au). These TMNP-2 complexes are shown to be remarkably efficient catalysts of several major green reactions.F irst, 4-nitrophenol (4-NP) reduction by NaBH 4 in water was used as am odel NP surface reaction to demonstrate the catalyst efficiencya nd compare all of these metals with one another. Then RuNP-catalyzed transfer hydrogenation of nitrobenzene with i-propanol as the hydrogen source in water/i-propanol, PdNP-catalyzed Suzuki-Miyaura crosscoupling reaction between bromobenzene and phenylboronic acid in water/EtOH, and CuNP-catalyzed azide-alkyne 1,3cycloaddition (CuAAC, click) reaction in water were shown to work using extremely low amounts (down to afew ppm) of catalysts.

Thes ynthesis of the tris-trz-PEG ligand 2 starts with the preparation of tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol, [22] 1 (Figure 1a). Three clicked trz rings of 1,f ormed through CuAACr eactions, [23, 24] are amphoteric p-electronrich aromatics that are biocompatible and stable toward both oxidizing and reducing agents.T hey are neutral and weak ligands for TMNP core surfaces,b ut provide stabilization of TMNPs,o wing to their bulk and compared to monodentate ligands. [25,26] This ligand is not water soluble,however, and the pursuit of green chemistry has led us to search catalysts in aqueous solution. To this end, aW illiamson reaction was conducted between 1 and chlorinated PEG 2000 (mPEG2000-Cl) to form ligand 2 that contains both the tristrz ligand and aw ater-solubilizing and biocompatible PEG chain. See the Supporting Information (Section 2) for the details.

Thes ynthesis of the family of TMNP-2 (with Fe,C o, Ni, Cu, Ru, Pd, Ag, Pt, and Au)was carried out in water at r.t. in the presence of the ligand 2 by NaBH 4 reduction of the transition metal salts followed by dialysis (Figure 1b;S upporting Information, Section 3). Both the trz groups of the tris-trz ligand and the PEG 2000 polymer are acting as weak ligands for the TMNP-2,whereby the synergy between weak, but multidentate,TMNP surface coordination and the overall large bulk permit the stabilization of these TMNPs (Figure 1b). Although the neutral nitrogen ligands are known to be better ligands than the neutral oxygen ligands,t he electronic delocalization within the trz ligands very much weakens the nitrogen donor ability,w hich should favor catalytic reactions by easy ligand substitution by substrates for surface catalysis.T he thermal stability of the TMNP-2 in water is ascertained by the lack of aggregation throughout catalytic experiments,e ven upon heating under inert atmosphere (see below).

Forinstance,with AuNP-2,refluxing the aqueous solution for 5hours did not provoke aggregation or any change of the SPB at 515 nm (Figure S15). Moreover,a lthough the large class of AuNPs with thiolate ligands contain Au I surface atoms,i nt he present case the X-ray photoelectron spectroscopy (XPS) signals at 84.05 eV for Au 4f 7/2 of AuNP-2 clearly show the presence of only Au 0 surface atoms (Figure 2a and S16). We selected the 4-NP reduction to 4-AP by NaBH 4 in water catalyzed by TMNPs [Eq. ( 1)] as as tandard reaction that can be used to evaluate the potential of the new ligand 2 to promote catalytic activity at the surface of TMNP-2.T his homogeneous reaction is simple,w ithout side paths,a nd easily monitored through UV/Vis spectroscopy by the decrease of the strong adsorption of the 4-NP anion at 400 nm. [27-29] TheB allauff group has shown that the mechanism (although unknown) involves rearrangement of the substrates 4-NP and NaBH 4 at the AuNP surface according to the Langmuir-Hinshelwood (LH) kinetic model, that is,t he diffusion of the reactants is fast compared to the rate-limiting substrate rearrangement at the AuNP surface. [27] TheA uNP-2 displays as urface plasmon band (SPB) at 515 nm in the UV/Vis spectrum, and ac ore size of 2.9 AE 0.3 nm in TEM (Table 1; Supporting Information). First, the 4-NP reduction in water catalyzed by AuNP-2 was conducted [Eq. ( 1)],a nd the reaction rates show that the AuNP-2 is one of the most efficient catalysts known (k app = 4.37 10 À2 s À1 ), compared with other catalysts from the literature (Supporting Information, Table S2). In addition, no induction times are found for the AuNP-2,a lthough the latter was observed in previous studies of thiolate-AuNPs and citrate-AuNPs. [30] Thev ery high reaction rates observed here,a nd the absence of induction time,r eveal the successful design of AuNP-2 as very efficient catalysts,a se xpected from the weak bonding ability of the trz-and PEG-coordination to AuNPs.The catalyst AuNP-2 was recycled five times with reaction rates that decreased only overall by less than 20 %, showing good stereoelectronic stabilization by the ligand 2, although the catalyst undergoes Ostwald ripening illustrated by the core size increase and slight variations by afew nm in the SPB.T his structural change is due to catalysis at the AuNP-2 surface, introducing the 4-AP product as aligand. Precipitation is never observed, however. Finally,w ec ompared 4-NP reduction catalyzed by AuNP-2 and AuNP-3,t he latter being stabilized by the ligand trz-PEG 2000, 3,which contains asingle trz ligand (Figure S10).

In this way,t he goal was to examine the influence of the multiplicity of the mono-versus tris-trz ligands containing the same PEG tail. Theresults indicate that the catalysis of 4-NP was significantly faster with AuNP-2 (k 1 = 0.410 Ls À1 m À2 ) than with AuNP-3 (k 1 = 0.253 Ls À1 m À2 ), showing the positive influence on catalysis of the tris-trz ligand bulk in 2 near the AuNP-2 surface.

We then extended the use of 2 to the synthesis of TMNP-2 with both cheap,a bundant metals (Fe, Co,N i, and Cu), and some other second-and third-row noble transition metals (Ru, Pd, Pt, and Ag) in the same manner as for the abovementioned preparation of AuNP-2 (Figure 1b). Interestingly, most of the TMNPs were formed with 2 in their nanocluster size (< 2nm), except the CoNPs and AgNPs which were slightly larger than 2nm(Table 1). This small size is advantageous for catalysis because the majority of atoms (54-70 %) are located on the TMNP surface for these metals (Fe, Ni, Cu, Ru, Pd, and Pt), forming monodispersed TMNP-2 cores with diameters smaller than 2nm(Figure 2b-e;Supporting Information, Section 3). Thus,t he catalytic properties of these TMNP-2 were also evaluated for the model 4-NP reduction with NaBH 4 [Eq. ( 1)].

Fort he group of first-row NPs,t he induction time was observed in all the cases,a nd these TMNP-2 exhibited the reaction rate order of Cu > Co > Fe > Ni in k 1 (k 1 = k app /S, S being the NP core surface area). [27, 28] Interestingly,noSPB of CuNP-2 was observed, whereas aS PB at 590 nm was observed for large CuNPs in the absence of 2 (Figure S18). Indeed, the SPB is absent in the UV/Vis spectra of the very small nanoclusters,i nw hich the molecular structure dominates. [31, 32] CuNP-2,with its small size (1.4 nm), presented no SPB,a nd showed ar eaction rate of k 1 = 1.75 10 À3 Ls À1 m À2 .

Other noble metal NP-2 (Au, Pd, and Pt) catalyzed the 4-NP reduction very well, using only 0.2 mol %catalyst, and no induction time was observed. In this category,t he reaction rate k 1 decreased with the order of Au > Pd > Pt > Ag. In the group 11 (Cu, Ag, and Au), from the first to the third row of transition metals,t he induction time decreases,a nd the reaction rates greatly increase,w hich is best taken into account by the increased facility of oxidative addition in the catalytic mechanism for heavier late transition metals (Table 1). ForR uNPs,e xceptionally small sizes (1 nm) and remarkably high reaction rate constants were observed (k 1 = 1.26 10 À2 Ls À1 m À2 ), ranking third best among these TMNP-2.Altogether,the tris-trz-PEG amphiphilic ligand 2 stabilized very small, monodispersed TMNP-2 with high efficiencies,as shown in the comprehensive comparisons of the recent literature for reaction rate constants of TMNP-catalyzed 4-NP reduction reactions with various stabilizers (Table S3). Note that, although the first-row transition metal NP-2 complexes exhibited high efficiencies in the 4-NP reduction when compared to other reported catalysts,t heir catalytic activities were still much lower than those of the noble metal NP-2.

Forfurther catalytic investigations,wethen selected three of the most efficient TMNP-2 (Cu, Pd, and Ru), AuNP-2 having already been shown to exhibit excellent catalytic activity for 4-NP reduction (see above).

CuAAC [23, 24] is well established as one of the most useful reactions in organic synthesis,materials science,and biomedical sciences.Recently,ithas also been shown that CuNPs are active catalysts for this reaction. [33-38] CuNP-2 was tested here as ac atalyst for AACb etween benzyl azide and phenylacetylene [Eq. ( 2)],a nd found to be highly efficient. This reaction was quantitatively achieved at 35 8 8Cf or 24 hu sing only 20 ppm of Cu from CuNP-2,l eading to an exceptional TONof28000 and TOFof1170 h À1 (Table S4). This is one of the best results ever obtained using CuNP catalysts.

Fort he investigation of the actually active species,X -ray photoelectron spectroscopy (XPS) of CuNPs was conducted (Figure 3). Them ain Cu peak, Cu 2p 3/2 ,i sf ound at binding energy (BE) of 932.6 eV (Figure 3a). Thevery weak satellite at around 945 eV gives the first indication of Cu I and the absence of Cu 2+ .Other indications for assignment to Cu I are on one hand the Cu 2p 3/2 peak at ar elatively high FWHM compared to the C1speaks (2.3 eV vs. 1.4 eV; Figure 3a and S45), and on the other hand the modified Auger parameter calculated from the Cu LMM (Figure 3b)t hat is assigned to Cu I (Supporting Information, Section 5). All of these data showed that the catalyst was in its classic Cu I state. [23, 24] It is unavoidable that the CuNPs surface is oxidized by molecular oxygen from the air,and the active Cu I species is thus formed in the native oxide layer on the Cu surface through comproportionation of Cu 0 and Cu II ,e ven if caution is taken to remove air.R ecycling experiments using 100 pm of Cu from CuNP-2 provided yields larger than 80 %d uring at least four successive recycling experiments,showing the good stability of the catalyst CuNP-2. TMNP-2 Amount [a] [mol %]

D core [b]
[nm]

t 0 [c]
[s]

k app [d] [10 À3 s À1 ] k 1 [e]
[L s À1 Thep alladium-catalyzed Suzuki-Miyaura reaction is one of the common cross carbon-carbon coupling reactions. [39-42] Thus,catalysis of this reaction with ppm amounts of Pd is an ongoing challenge, [43, 44] and only afew works are known to use this approach. [21, 45-47] PdNPs are av aluable option, because toxic ligands that are often employed in efficient Pd catalysis are avoided with PdNP catalysts.T he 1.5 nm core-sized PdNP-2 with Pd 0 surface (from UV/Vis spectroscopy;F igure S20) catalyzed the Suzuki-Miyaura reaction between bromobenzene and phenylboronic acid using down to 10 ppm Pd per mol substrate [Eq. ( 3)],reaching aTON of 89 000 and aT OF of 3700 h À1 in 24 ha t8 08 8Ci nw ater/EtOH mixture (Supporting Information, Section 6). After the reaction, no aggregation of PdNPs was observed, indicating the very good thermal stability of the PdNP-2.I na ddition, recycling the PdNP-2 catalyst in 0.1 mol %f or this reaction gave yields of 87 %orabove up to the 5 th successive recycling run, with only as light increase of the PdNP-2 core size from 1.5 to 1.8 nm (Figure S54) without any aggregation.

Another challenging example is the catalysis of transfer hydrogenation (TH). TH refers to the addition of hydrogen to am olecule using an on-H 2 hydrogen source (such as isopropanol). It is ac onvenient, powerful, and green method to access various hydrogenated compounds. [48, 49] TheU V/Vis spectrum of the RuNP-2 confirms reduction to the Ru 0 surface following NaBH 4 reduction of RuCl 3 •x H 2 O (Figure S21). We found that the RuNP-2 efficiently catalyzed TH of nitrobenzene using H 2 O/isopropanol as the solvent at 80 8 8Ci nt he presence of the base with only 0.01 mol %o f catalyst at 80 8 8Cfor 24 h[Eq. ( 4)],leading to aTON of 2300 and TOF of 96 h À1 (Table S5). Recycling this catalyst with 0.1 mol %RuNP-2 provided aproduct yield of 85 %ormore up to the 3 rd successive recycling run.

In summary,l igand design for nanoparticle catalysis with very weak but multidentate Nand Oligands has been shown to apply to the stabilization and remarkable catalytic efficiency of very small, water-soluble TMNPs-2.T he favorable effect of the tris-trz ligand 2 over the less bulky,simple monotrz ligand 3 is illustrated by the increased reaction rate of AuNP-catalyzed 4-NP reduction observed with 2 compared to 3.The success of the ligand design involving 2 was exemplified with the catalysis by TMNP-2 of various major reactions that were conducted in water or aqueous media. This engineering efficiently applies to the first row transition metals,asshown with click chemistry and the reduction of the 4-nitrophenol pollutants to useful 4-aminophenol dyes.Italso applies to the noble transition metals with the use of only ppm amounts of TMNP-2 catalysts for transfer hydrogenation of nitrobenzene,r eduction of 4-NP,a nd cross carbon-carbon coupling.

Therecyclability studies were conducted using abiphasic organic/aqueous separation of products and subsequent addition of new reactants,w hich is ap otential means to reuse the catalyst in ac ontinuous flow-type arrangement. Many other reactions should benefit from this simple and general concept, operating under green conditions with ppm amounts of TMNP catalyst and in the absence of toxic ligands. So far, very few studies have demonstrated the possibility using only ppm amounts of metal, responding to the industrial limit of am aximum of 5ppm of residual metal in products, [21,45-47] and this new concept should enhance trends towards this goal.

From Mono to Tris-1,2,3-triazole-Stabilized Gold Nanoparticles and Their Compared Catalytic Efficiency in 4-Nitrophenol Reduction

■ INTRODUCTION

Gold nanoparticles (AuNPs) have received considerable scientific interests and are actively investigated in the areas of nanomaterials, 1 catalysis, 2 and biomedicine. 3 In the field of heterogeneous catalysis, exceptional activity has long been disclosed with very small AuNPs, especially with metal-oxidesupported AuNPs. 2 To obtain catalytically active AuNPs, stabilizers (dendrimers, polymers, ionic liquids (ILs), inorganic solid supports) are indeed playing a crucial role and eventually affect the catalytic properties. 4 Catalytic reactions typically occur at the AuNPs surface, although some strong ligands (thiolates, phosphines, phosphine oxides, etc.) inhibit the active surface sites, leading to negative catalytic effects. Thus, "green" ligands that involve mild NP stabilization in water and are easy to displace and eventually provide more surface active sites in catalytic processes are searched to further improve activity. This is the case for nitrogen donors that leave the metal site at the metal surface in the zero oxidation state without back bonding, that is, electron rich, which is potentially most favorable for catalysis.

4-Nitrophenol (4-NP) reduction by NaBH 4 to 4-aminophenol (4-AP) is among the most studied AuNP-catalyzed reactions, because its kinetics is easy to follow in aqueous media. 5 It is monitored by UV-vis spectroscopy, and the C t value represents the absorbance at 400 nm that corresponds to the nitrophenolate anion decreases with time along with the growth of a weak 4-AP band at 300 nm. This 4-NP reduction reaction catalyzed by NP catalysts is fitted with a pseudo-first-order kinetics with respect to 4-NP in the presence of excess NaBH 4 , leading to the determination of the rate constant k app = ln(C t /C 0 )/t. 2f This reaction was pioneered by Pal et al. in 2002, 6 and detailed kinetics studies by Ballauff's group have demonstrated that the mechanism involves rearrangement of the substrate fitting the Langmuir-Hinshelwood (LH) model with an induction time caused by dynamic restructuring of the NP surface. 7 This reaction provides a convenient way to examine the behavior of the stabilizing ligand at the NP metal surface including the facility of ligand displacement and catalysis on NP surface. Thus, in the present study we used this reaction in water to examine the efficiency of 4-NP reduction by NaBH 4 at the AuNP surface stabilized by 1,2,3triazole ligands.

In previous reports, we already used the well-known copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) reaction 8 to form weak 1,2,3-triazole (trz) ligands that mildly stabilize various AuNPs. 9 Among small transition metal NPs, 10 these trz-AuNPs have been shown to efficiently catalyze 4-NP reduction to 4-AP by NaBH 4 in water. 9-12 In particular, both mono-and tris-trz ligands with PEG tails were recently shown to stabilize AuNPs that catalyzed 4-NP reduction in water with excellent rates. 10 It has also been shown by Raman spectroscopy that the trz C-N and NN bonds are much closer to the AuNP surface than other ligand atoms, suggesting that the trz neutral ligands stabilize the AuNPs by coordination of their nitrogen atoms to the AuNP surface. 11 AuNPs stabilized by trz ligands present reaction rates for 4-NP reduction by NaBH 4 that are higher than those obtained with other ligands. In addition, AuNPs stabilized by trz ligands do not show induction times for this reaction, contrary to AuNPs stabilized by citrates and thiolates. 12 These features suggested that the weak trz ligands on AuNP surface were easily displaced by the 4-NP and NaBH 4 substrates that directly led to high reaction rates. Therefore, it was of interest to compare the AuNP stabilization and catalytic activities of various types of trz ligands. Here we are reporting the stabilization of AuNPs by mono-, bis-, and tris-trz and the influence of the trz denticity on the 4-NP reduction by NaBH 4 in water, also including comparison with current polyethylene glycol 2000 (PEG) and polyvinylpyrrolidone (PVP) AuNP stabilizers. These results should be informative concerning the benefit of AuNP stabilization by multidendate nitrogen ligands and catalytic properties herewith.

■ RESULTS AND DISCUSSION

We started the study by the parent trz 1 (Figure 1). Indeed, the stabilization of AuNPs in water upon NaBH 4 reduction of HAuCl 4 in the presence of 1 very much depends on the reaction stoichiometry. With the stoichiometry 1:1 trz/HAuCl 4 , aggregation of the formed AuNP-1 upon adding NaBH 4 quickly occurs as visually observed while stirring in water at room temperature (rt). This is confirmed by the weak surface plasmon band (SPB; Figure 2a, and Supporting Information), although a reaction rate in 4-NP reduction was obtained upon ultrasonic dispersion of AuNP-1 (Table 1). The use of 3 equiv of 1 versus HAuCl 4 to stabilize AuNPs resulted in considerably slowing this aggregation, and the AuNP-1 were now stable for several hours and could thus also be used to study their catalysis of 4-NP reduction. We then turn to the use of 1,3di(1H-1,2,3-triazol-1-yl)propane, 2, as the AuNP stabilizing agent with the hope of taking advantage of the stabilizing chelation of the AuNP surface by the bis-triazole ligand. This attempt was somewhat successful, because the AuNP-2 were stable overnight, allowing the records of AuNP-2 SPB and catalytic 4-NP reduction process by UV-vis spectroscopy (Table 1). The SPBs of AuNP-2 with various amounts of ligand 2 are much smaller than that of Au-1, while the 4-NP reaction rates are lower with AuNP-2 than with AuNP-1. These results suggested that the ligand 2 is a much better AuNP stabilizer than the ligand 1, as indicated by the smaller AuNP size and lower reaction rate of 4-NP reduction, although the main drawback is again the lack of long-term stability.

Polyethylene glycol (PEG) is a liner and green polymer that has long been recognized as an NP stabilizer and a phase transfer agent. 13 It has also been used to encapsulate some molecules for further catalytic processes, and these properties depend on the polymer chain length. 14 This typical PEG 2000 polymer (Mw = 2000, n = 44) was then used to stabilize AuNPs, and the stable PEG-stabilized AuNP-3 obtained presented a SPB at 527 nm with a core size measured by transmission electron microscopy (TEM) of 8.3 ± 0.5 nm, similar to those of AuNP-2 (Figure 2c, Table 1 and Supporting Information). The 4-NP reduction was then successfully conducted, yielding a reaction rate of k app = 18.3 × 10 -3 s -1 that is higher than some of the known published literature values (see the comparison in Table S1). In addition, an induction time was not observed, indicating that the weak Au-O bonds interactions in PEG-encapsulated AuNPs were easily displaced, favoring 4-NP reduction.

Trz with a PEG chain was then used with the idea that coordination of the triazoles on some AuNP surface atoms would leave the rest of the surface atoms only weakly stabilized by the weak ether ligand of the PEG. With this goal, the known monotrz-substituted PEG 4 was then used to encapsulate AuNPs, and under conditions identical to the above-mentioned AuNP preparations the use of 1 equiv of the monotrzsubstituted PEG 4 led to the known AuNP-4 with the SPB of 524 nm and AuNP core size measured by TEM of 5.8 ± 0.4 nm. 10 The 4-NP reduction rate catalyzed by AuNP-4, 20.9 × 10 -3 s -1 (k app ), was higher than that of AuNP-3, but the AuNP size was larger than expected. To obtain smaller AuNPs, 3 equiv of ligand 4 versus HAuCl 4 was used, and the core size of AuNP-4 was reduced to 3.1 ± 0.3 nm (Figure 2d) with a SPB of 515 nm in the UV-vis spectrum. The 4-NP reaction rate increased to 24.9 × 10 -3 s -1 (k app ), 10 which is one of the highest records among rates of 4-NP reduction compared with the recent literature (Table S1).

Recently active studies of micellar catalysts in water (e.g., dendrimer-encapsulated NPs) were reported, and these catalysts usually showed enhanced catalytic activities and selectivities. However, NP formation in micelles or inverted micelles and catalysis therein are very dependent on the stereoelectronic parameters of the stabilizing agent. 15 Moreover with the inspiring results obtained above we then envisaged that a water-soluble amphiphilic ligand containing hydrophobic tris(1,2,3-triazolyl) on the one side and a hydrophilic PEG chain on the other side to stabilize AuNPs, forming a micellar AuNP catalyst, would further improve the catalytic efficiency. The known ligand 5 was expected to fulfill all the important features with the AuNPs including small size (3 nm) and improved reaction rates on the AuNP surface. The optimizations of Au and ligand mole ratios with variations of SPBs, TEM sizes, and 4-NP reaction rates were thus investigated, and a best result was obtained with the stoichiometry of ligand 5:A u III of 1:1 with the smallest AuNP core size and highest reaction rate. 10 The positive influence on catalysis of the tris-trz ligand bulk in 5 near the AuNP-5 surface was also confirmed by comparison between the multiplicity of the mono-versus tris-trz ligand containing the same PEG tail (AuNP-4 and AuNP-5, respectively). 10 Comparison between AuNP-5 stabilized by the ligand 5 and AuNP-6 stabilized by the widely used commercial polymer polyvinylpyrrolidone 16 (PVP, Mw = 10 000, 90 monomer units) showed that although AuNP-6 was smaller than AuNP-5 (2.2 ± 0.4 vs 2.9 ± 0.3 nm), the reaction rate was much lower with AuNP-6 (15.2 vs 43.7 × 10 -3 s -1 in k app ), indicating that the stronger Au-N and Au-O bonds in AuNP-6 than in AuNP-5 ensured smaller AuNP formation but also inhibited the surface catalytic efficiencies (induction time). Also, in the 4-NP reduction catalyzed by AuNP-5-0°Ca t2 0°C, a short induction time of 40 s was noticed, probably resulting from higher order in more compact ligand distribution on the AuNP surface. The lack of induction time for AuNP-1, AuNP-2, and AuNP-3 is taken into account by the very small sizes of the ligands in the two former AuNPs and for the very weak AuNPligand bond for the latter. These data demonstrate the successful design of this well-defined, new, green, and amphiphilic surface ligand 5. Previously it has been reported that the intermediate Au I state played a critical role in controlling the morphologies of AuNP synthesized from Au III ions. 17 Indeed, some encouraging results have been obtained by using Au I as precursors in the presence of ligands to form AuNPs with controlled size, shape, and crystallinity. 18 Thus, Au I precursors with ligands make it possible to prepare AuNPs under mild conditions without a reducing agent. We then first investigated the use of gold(I)chloro(tetrahydrothiophene) [AuCl(SC 4 H 8 )] as a Au I precursor to illustrate the effect of the nature of the Au oxidation state on the AuNP size and catalytic properties in the presence of ligand 5. A Au(I) complex of 5 was obtained by ligand substitution in CH 2 Cl 2 , but this complex was not stable at rt (Scheme 1). On the one hand, after careful removal of CH 2 Cl 2 instead of adding water, AuNP-5-THT was obtained as purple solution after dialysis. However, at variance with previous reports, the present process led to the formations of AuNP-5-THT with a relatively large SPB (556 nm) and NP sizes (Table 1), and wide AuNP size distribution due to the usage of the weak ligand 5. 18 On the other hand, although large AuNP-5-THT were obtained, the use of AuNP-5-THT to catalyze 4-NP reduction was very successful, leading to a surprising value of K app = 17.5 × 10 -3 s -1 . This rate constant value is higher than that obtained with small AuNPs stabilized by PVP (AuNP-6), and no induction time was observed, suggesting both the promoting effect ligand 5 in 4-NP reduction and the ligand weakness upon easy displacement by substrates.

We also compared AuNP-5 synthesis at rt and 0 °C (icewater bath), namely, AuNP-5 and AuNP-5-0°C, respectively, to investigate the temperature effect in AuNP synthesis and catalytic properties in 4-NP reduction. Previously, it was established that a lower synthesis temperature favored the formation of two-dimensional-like nanostructures. 19 In the present case, AuNP-5-0°C shows a broad SPB (main at 538 nm) in the UV-vis spectrum, and TEM images show various shapes of anisotropic AuNPs (e.g., platelike and/or spherical particles) with a broad size distribution. The increase of temperature results in the decrease of particle size and narrows size distribution, whereas decrease in reaction temperature results in increase in particle size and broad size distribution with anisotropic AuNP nanostructures. 20 These phenomena were observed in many cases, because reactant depletions took place faster with higher reaction rates caused by high temperature, leading to the formation of smaller nanoparticles. 19,21 ■ CONCLUDING REMARKS Simple trz ligands stabilize AuNPs, but only the increase of ligand denticity to two and especially three insures full AuNP stabilization. Such AuNPs form with small core sizes of ∼3 nm, which allows observation of the plasmonics. Interestingly, the use of amphiphilic mono-and tris-trz ligand provides micellar AuNPs in a rather similar way to amphiphilic micellar dendrimers used in efficient catalysis, 22 but of much simpler synthesis. The 4-NP reduction in water is an excellent tool to investigate the AuNP-ligand bonding in water-soluble NPs, and indeed very high rate constant values were obtained in comparison with classical PEG-AuNPs and PVP-AuNPs. This technique also highlights the privileged tris-triazole ligand 5 (and presumably other tris-trz and tris-nitrogen ligands) over other triazole-type AuNP ligands for 4-NP reduction. This study opens the route both toward investigation of various other NP stabilizers and ligands for NP surface catalysis and toward micellar-type NP catalysts. 23 ■ EXPERIMENTAL SECTION General Data. All solvents and chemicals were used as purchased, unless elsewhere noted. Milli-Q water (18.2 MΩ) was used for all the AuNP preparations. Prior to the synthesis, the Schlenk flask was washed with a solution of aqua regia (HCl/HNO 3 = 3:1 v/v) to remove any traces of metal residue. NMR spectra were recorded at 25 °C with a Bruker 300 (300 MHz) spectrometer. All the chemical shifts are reported in parts per million (δ, ppm) with reference to Me 4 Si for the 1 H and 13 Synthesis of 1,3-Diazidopropane. A dried flask was charged with dimethyl sulfoxide (40 mL) and NaN 3 (1 g, 14.85 mol) under N 2 . 1,3-Dibromopropane (1 g, 4.95 mmol) was added by syringe, and the mixture was stirred for 24 h at rt. Water was added in portions (5 × 20 mL) while allowing the reaction mixture to cool to rt between portions. The mixture was extracted with 3 × 50 mL of Et 2 O. The extracts were combined and washed with water (3 × 50 mL) and brine (150 mL). The ether layer was separated and dried over MgSO 4 . The solvent was removed in vacuo to yield a clear oil. Yield: 90%. 1 H NMR (CDCl 3 ): δ ppm 3.43 (t, 4H), 1.84 (quintet, 2H).

Synthesis of 1,3-Di(1H-1,2,3-triazol-1-yl)propane, 2. A dried flask was charged with 1,3-diazidopropane (850 mg, 1 equiv) and ethynyltrimethylsilane (1.65 g, 2.5 equiv) in the presence of THF under N 2 . An aqueous solution of CuSO 4 (0.2 equiv, 10 mol % per branch) was added, and stirred for 30 min. Afterward, NaAsc (10 equiv per branch) was added dropwise. The mixture was then allowed to stir for 24 h at rt. Then, the mixture was then filtered and washed, and the solvents were removed in vacuo. Then MeOH and K 2 CO 3 was added, and the mixture was stirred for 24 h at rt to yield a white solid product. Yield: 76%. 1 Synthesis of the 1,2,3-Triazole-mPEG Ligand, 3. In a dried flask, trimethylsilyl azide (0.2 mL, 1.5 mmol) was added to a mixed dimethylformamide/MeOH solution (3 mL, 9:1) that contained the catalyst CuI (5.8 mg, 0.03 mmol) and ethynyl-mPEG (1000 mg, 1 mmol) under N 2 . The reaction mixture was stirred at 90 °C overnight. Then the mixture was cooled to rt, filtered, and the solvents were removed in vacuo. Then, the residue was dissolved in CH 2 Cl 2 and washed three times with water. The organic phase was collected and dried over anhydrous sodium sulfate to yield the white solid product. Yield 65%. 1 H NMR (CDCl 3 , 200 MHz) 7.67 (1H, H of triazole), 4.66 (2H, CH 2 -triazole), 3.58

(176H, -CH 2 CH 2 O-), 3.32 (3H, -OCH 3 ).
Synthesis of AuNP-L. Generally, the gold precursor (1 equiv) in 1 mL of water was added to a solution that contained 1 or 3 equiv of ligand (1 or 3 triazole per Au) in 5 mL of water. The mixture was allowed to stir for 15 min. Then, a freshly prepared aqueous solution of NaBH 4 (10 equiv) was added to the solution dropwise, and the solution was continuously stirred for another 30 min. Dialysis was conducted for 24 h to remove the excess of ligand and NaBH 4 . The AuNP-L was kept in aqueous solution for characterization and used as catalyst. The AuNPs stabilized by PEG were prepared under identical condition, except that 1 equiv of PEG per equiv of Au 3+ was used.

Reduction of 4-NP by NaBH 4 (at 20 °C). The catalytic efficiencies of the catalysts AuNP-L were tested using the model reaction of 4-NP reduction with an 81 equiv excess of NaBH 4 that is fast, simple, and well-controlled. Generally, 4-NP (1 equiv) was mixed with NaBH 4 in water under air. The color of the solution changed from light yellow to dark yellow due to the formation of 4-nitrophenolate ion. Then a solution containing AuNP-L (0.2 mol %) was added to the mixture. The solution quickly lost its dark yellow color with time, and the progress of the reaction was monitored by UV-vis spectroscopy (250-550 nm, 40 s for each run). ABSTRACT: The copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) using the conventional Sharpless-Fokin catalyst that consists of CuSO 4 +N a ascorbate, the most well-known and used "click" reaction, is considerably accelerated by the addition of a tris(triazolyl)-poly(ethylene glycol) (tris-trz-PEG) amphiphilic ligand in water under ambient conditions. Only parts per million amount of Cu I were necessary to reach quantitative yields with TONs up to 86000 and TOFs of 3600 h -1 . The ligand was fully recycled, and the catalyst was reused at least six times without decomposition. Large-scale syntheses were also successfully achieved with 93% yield. The catalyst was applied to the efficient synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties.

■ INTRODUCTION

The concept of "click chemistry" proposed by Kolb, Finn, and Sharpless in 2001 1 has undoubtedly revolutionized molecular engineering science. Following the seminal and independent report by the Sharpless-Fokin 2 and Meldal 3 groups in 2002 of copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) selectively yielding 1,4-disubstituted 1,2,3-triazoles, CuAAC has been applied to an enormous range of new syntheses and applications to macromolecules and nanomaterials. 4-7 For such CuAAC reactions, the catalytically active Cu I species was usually generated from the cheap and easily available mixture of CuSO 4 and sodium ascorbate (NaAsc), known as the Sharpless-Fokin catalyst. The CuAAC reaction rate is low if the catalyst is not presented in high concentration and in the presence of activating ligand, however. For practical reaction processes, in most of the cases the Sharpless-Fokin catalyst is used in relatively large quantities in order to avoid the formation of the 1,5-isomer 8a and to keep an acceptable reaction rate. 8b,c The problem then remains to remove the copper ions, which limits this "click" chemistry in electronics and biomedicine. 9 To overcome these difficulties, some ligands have been shown to considerably accelerate the reactions and reduce the catalyst amounts. Among them, nitrogen-based ligands such as polytriazoles 10,11 and tris(2aminoethyl)amine derivatives (tren) 12-14 have been found to be excellent, reducing the amount of Cu I catalyst to an order of 1% or less. Recently it was reported that a recyclable dendritic nanoreactor containing intradendritic triazoles 9 and the poly(Nisopropylacrylamide-co-N-vinylimidazole) polymer 15 promoted CuAAC reactions in water and in t-BuOH/H 2 O, respectively, down to the remarkable parts per million level of Cu I catalyst under the conditions of in situ Cu 2+ reduction using NaAsc. With such low amounts of catalysts and exceptional efficiencies, CuAAC reactions in aqueous solution under mild reaction conditions have effectively contributed to the pursuit of "green chemistry" with potential industrial applications. Nevertheless, only very few useful examples of synthetic applications under such conditions are known. In addition, in the case of the dendrimer, 9 such efficiency is associated with the complicated and time-consuming synthetic procedure of the catalyst. In this context we now address the utilization of an amphiphilic tripodal ligand, tris(triazolyl)-poly(ethylene glycol) (tris-trz-PEG), 16 the synthesis of which is simple, "green", and biocompatible. Its catalytic efficiency is similar to that of the dendrimer, 9 promoting the use of the conventional Sharpless-Fokin catalyst to the high efficiency of parts per million of Cu I in water for various organic syntheses of medicinal, catalytic, targeting, and labeling interests.

■ RESULTS AND DISCUSSION

The preparation of the new "click" catalyst involves addition of CuSO 4 •5H 2 O under nitrogen to an aqueous solution containing the amphiphilic tris-trz-PEG ligand and then in situ reduction of the precatalyst PEG-tris-trz-Cu 2+ to the PEG-tris-trz-Cu I catalyst by dropwise addition of NaAsc (Scheme 1 and Supporting Information).

The synthetic procedure has been monitored by UV-vis (Figure 1) and 1 H NMR spectroscopy (Supporting Information). In UV-vis spectroscopy, an aqueous solution of CuSO 4 • 5H 2 O has an absorption in the range of 700-800 nm (Figure 1, insert), which is attributed to the Cu 2+ d-d transition. 17 Upon coordination of Cu 2+ to the triazole rings this absorption disappears. After further reduction by NaAsc (10 equiv/mol of CuSO 4 ), the PEG-tris-trz-Cu I complex exhibits a moderately intense band in the range between 300 and 400 nm (main absorption at 370 nm, Figure 1) which is assigned to a metal to ligand charge transfer (MLCT) transition. 18 These phenomena have also been confirmed by 1 H NMR spectroscopy using D 2 O as the solvent (Figure S1 in the Supporting Information). After addition of Cu 2+ , the NMR signal of the triazole proton of the tris-trz-PEG ligand vanishes due to the paramagnetism of the Cu 2+ species, suggesting complexation. 9 When NaAsc is added, the NMR signal of the triazole proton of the tris-trz-PEG ligand reappears, but it is shifted to 8.19 ppm in comparison to the initial proton signal at 8.04 ppm (Figure S1), indicating that the triazole rings are coordinated to Cu I . 9,19 The efficiency of this new CuAAC catalyst was then tested using the standard "click" reaction between benzyl azide and phenylacetylene with various amounts of catalyst in neat water as the solvent (eq 1 and Table 1). When these reactions were performed in the presence of 2000, 200, and 100 ppm of PEGtris-trz-Cu I catalyst, respectively, in water at 35 or 30 °C, the crude reaction yields after 20 h were quantitative, and the desired 1,2,3-triazole was obtained in 97% yields (entries 1-3). A decrease in the catalyst amount to 50 ppm also resulted in quantitative conversion and 95% isolated yield at 35 °C (entry 4). Although the catalyst amount has been successfully decreased to 20 or 10 ppm (entries 5 and 6) without quantitative conversions, excellent yields are obtained, leading to TONs up to 86000 and TOFs up to 3600 h -1 . When the catalyst was reduced to 4 ppm (entry 7), the yield decreased but resulted in TON and TOF values that were still higher than those obtained with 20 ppm. The best conditions for this CuAAC catalytic system are at 50 ppm and 35 °C for 20 h, leading to full conversions and high isolated yields. A large-scale reaction under these conditions was Scheme 1. Synthesis of the PEG-tris-trz-Cu I "Click" Catalyst also successfully conducted, and a similar isolated yield (93%) was obtained (entry 4). Moreover, recycling the catalyst was also successful, because the amphiphilic tris-trz-PEG ligand is insoluble in cold diethyl ether, allowing complete extraction of the "click" products from the aqueous solution while the catalyst remained in the water phase. In this way, the catalyst was recycled at least six times without change of ligand structure during the CuAAC reactions (Figure S2 in the Supporting Information). However, a slight decrease in the yields was observed (Table S2 in the Supporting Information), which was due to the unavoidable lost of copper ions that were stoichiometrically trapped inside the product through interaction with the trz group (before being extracted with an ammonia solution). 20 It was then of interest to investigate the underlying reason(s) for such an efficiency in the CuAAC reactions in water using such low amounts of PEG-tris-trz-Cu I catalyst. To this end, Cu I stabilized by PEG 2000 (B), monotrz-PEG (1 and 3 equiv for C and D, respectively), and tris-trz-PEG (E) were compared with the original neat Cu I (CuSO 4 + NaAsc, A) catalyst for the CuAAC of benzyl azide and phenylacetylene in water under identical conditions. First, the original Cu I and PEG-stabilized Cu I species were compared, because the tris-trz-PEG has a PEG tail. The water-soluble and eco-friendly PEG is used extensively as a solvent or cosolvent in water for a variety of purposes due to its phase-transfer catalytic nature that is efficient in organic synthesis. 21 Previously, it was shown that "click" synthesis of 1,4disubstituted 1,2,3-triazoles proceeded in good yields using CuSO 4 + NaAsc in PEG 400/water under mild conditions for a short time, due to very efficient activation by PEG 400. 22-25 However, this effect is not observed in the present study, because similar yields were obtained on comparison of A and B with different catalyst loadings. It appears that the concentration of PEG played a key role in the previous studies (PEG 400/water = 1/1, v/v). 22-25 Here the present PEG concentration is too low to provide such an effect, and therefore the PEG ligand does not lead to a good yield. When the monofunctional 1,2,3-triazole terminated with PEG 2000 (PEG-monotrz-Cu I , 1 equiv, C), 26 was introduced, the yields increased, especially with low catalyst amounts (i.e., 26.5% vs 5% at 100 ppm). This confirmed that the nitrogen-based ligand served as a rate accelerator in this Cu I catalysis, resulting in increased yields. 4-7 When a stoichiometric amount of monotrz-PEG vs Cu 2+ was used in the synthetic procedure (3 equiv, D), the yields also greatly increased in comparison to those of the reactions catalyzed by A with various catalyst loadings (i.e., 66.7% vs 5% at 100 ppm; 34.0% vs 0% at 50 ppm). Surprisingly, quantitative conversions with excellent isolated yields were generally obtained at 2000, 200, 100, and 50 ppm using the PEG-tris-trz-Cu I catalyst (E) under the present conditions. It thus appears that a strong chelation effect becomes more and more important as the concentration decreases. 4-7,10,11 In the cases of Cu 2+ in neat water and Cu 2+ in water in the presence of PEG and 1 equiv of monotrz-PEG, when NaAsc was added, the color of the aqueous solution changed very quickly from colorless to light yellow. This was not the case for Cu 2+ in water in the presence of the ligands that are in a stoichiometric ratio of trz to Cu 2+ (3 equiv of monotrz-PEG and 1 equiv of tris-trz-PEG). In these cases 1/2 h or more was required to change from colorless to light yellow. The differences in Cu 2+ reduction rates are seemingly due to the increased electron density brought about on Cu 2+ upon complexation by all trz ligands, making reduction of Cu 2+ thermodynamically and subsequently kinetically more difficult. Altogether, as depicted in Figure 2, the high efficiency of these "click" reactions catalyzed by very low amounts of PEG-tris-trz-Cu I catalysts benefit from (i) the chelation effect, (ii) the amphiphilicity of the tris-trz-PEG ligand containing a tris-triazole tripod that increases the electron density on the metal center, and (iii) a PEG chain allowing homogeneous "click" reactions in water.

Encouraged by the success of the initial efforts, the scope of applicability of this very low level amount of PEG-tris-trz-Cu I catalyst was explored with CuAAC reactions between various alkynes and organic azides in water (Table 2). As an inspection of Table 2 reveals, excellent yields were generally obtained in the CuAAC of a wide variety of alkynes with organic azides. In addition, in most of the studied cases, purifications of the products by silica chromatography were not necessary, because most of the "click" products are water-insoluble solids, and the excess alkyne was removed by simple solvent washing and eventually by recycling. Thus, these "click" products were obtained by a simple extraction-washing-filtration process, revealing the advantages of this low level of PEG-tris-trz-Cu I catalyst for CuAAC reactions in neat water.

As shown in Scheme 2, the catalyst PEG-tris-trz-Cu I was also successfully used to prepare functional materials, namely "click"triazole-functionalized 1-ethynylcyclohexanol (1;e q3 ) ,6monodeoxy-6-monoazido-β-CD (2; eq 4), p-bis(ferrocenyl-1,2,3-triazolylmethyl)benzene (3; eq 5), "click"-triazole functionalized 7-(propargyloxy)coumarin (4; eq 6), two kinds of 9triazolyl dendrimers (5 and 6; eq 7), "click"-triazole functionalized moxestrol (7; eq 8), and 3′-deoxy-3-azidothymidine (8;eq 9).

First, 1-ethynylcyclohexanol was chosen, because it has a simple structure, and it is known as an active metabolite of the old central nervous system depressant drug ethinamate. The "click" reaction with benzyl azide was achieved in excellent isolated yield (93%) using only 200 ppm at 35 °C for 20 h (Scheme 2, eq 3).

Cyclodextrin (CD) has been largely dominated by its unique ability to form inclusion complexes with guests fitting in their hydrophobic activity, 27,28 and its functionalizations have been a powerful means to improve its applications toward drug delivery, sensing or enzyme mimicking, pharmaceuticals, and biomedicine and also as catalysts of aqueous-phase metal-catalyzed organic reactions. 29-36 Previously, it has been shown by Ding's group that a water-soluble palladium complex based on 2 exhibited extremely high TONs and TOFs for Suzuki-Miyaura crosscoupling reactions in neat water. This was mainly attributed to the β-CD-fragment enhanced water solubility of the catalyst and accommodated the substrate through a recognition process, although the Sharpless-Fokin catalyst was used in high amount (10 mol %). 37 Now with the promotion of the amphiphilic tristrz-PEG ligand, only 300 ppm of the Sharpless-Fokin catalyst efficiently catalyzed the "click" reaction with 2 in 85% isolated yield (Scheme 2, eq 4). Furthermore, host-guest molecular interactions between β-CD and ferrocene derivatives 38 for nanoparticle catalysts in aqueous solution are also known, and recently this host-guest system was utilized in AuNP assembly for photothermal therapy. 39 Now the "click" synthesis of one of these host-guest system precursors, p-bis(ferrocenyl-1,2,3triazolylmethyl)benzene (3), was achieved using only 100 ppm per branch at 35 °C for 24 h with 83% isolated yield (Scheme 2, eq 5). It is expected that this material will be useful to complex β-CD in a host-guest assembly to stabilize metal nanoparticles for catalysis in aqueous solvents 38 and develop smart nanocarriers for intracellular diagnosis and therapy.

"Click"-triazole functionalized 7-(propargyloxy)coumarin (4) was also tested in the CuAAC "click" reaction with PEG-tris-trz-Cu I in water (Scheme 2, eq 6). Coumarin derivatives are often used for their antioedematous properties, and their flavor properties have rendered this family famous in the perfume industry. Moreover, coumarins are also known as fluorescence dyes. With 300 ppm of PEG-tris-trz-Cu I catalyst, this "click" product was isolated in 89% yield.

The CuAAC "click" reaction is a superb synthetic tool that has also been usefully and successfully applied to the synthesis of "click" dendrimers. 7,40 Following our original report of the first "click" synthesis of metallodendrimers, 19,41 iterative "click" constructions of metallodendrimers terminated by redox ferrocenyl groups and pyridyltriazole ligands were achieved. 42 Subsequently the use of these trz-metallodendrimers in redox sensing 20 and catalysis of carbon-carbon cross-coupling reactions 42,43 attracted increasing attention. However, the constructions of multiple and pure 1,4-regioisomers of 1,2,3triazole-terminated "click" dendrimers are rather difficult, unless specificCu I catalysts are designed or/and used with high catalyst loading in organic solvents at relatively high temperature. In addition, "click" dendrimers tend to trap organic solvents and other impurities such as Cu ions that are more or less difficult to remove. The present study using the PEG-tris-trz-Cu I catalyst allows "click" synthesis of 9-ferrocenyltriazole dendrimer 5 and 9-pyridyltriazole dendrimer 6 in excellent yields with 100 ppm of Cu I per azido branch of catalyst under ambient conditions in water (Scheme 2, eq 7). Moreover, the purification of the dendrimers was achieved by straightforward solid/liquid phase separation. After the reaction, dendrimers 5 and 6 were separated from water as light yellow waxy solids sticking to the wall of the glass vessel and magnetic stirring bar by simply removing the liquid water phase and washing with pentane.

Moxestrol is known as a synthetic steroidal estrogen for the treatment of menopausal symptoms, and it is one of the most potent estrogens known. The natural alkyne of moxestrol has afforded easy functional ability for various medicinal applications. Herein we use the easily accessible "click" means to functionalize this useful material, with 500 ppm of PEG-tris-trz-Cu I in only water at 35 °C for 48 h with 100% conversion and 93% isolated yield to the desired product 7 (Scheme 2, eq 8).

Another key important natural product, 3′-deoxy-3-azidothymidine (AZT, zidovudine), a nucleoside-analogue reverse transcriptase inhibitor, was the first approved antiviral product for the treatment of human immunodeficiency virus (HIV). The 3′-azido group of AZT has afforded its potential application to HIV RT binding, 43 and its "click" functionalization has shown to be a convenient tool for the synthesis of novel nucleoside inhibitors with low to submicromolar potencies against HIV-1, 44,45 novel fluorescent markers, and cytostatic agents. 46,47 Moreover "click" functionalization of AZT to form nucleoside-based bioconjugates has also recently been employed as a biological CO tracer. 48 Herein, we quote an example of these useful AZT-derived 1,2,3-triazoles by synthesizing 8 using 500 ppm of PEG-tris-trz-Cu I in only water at 45 °C for 48 h with 100% conversion and 89% isolated yield (Scheme 2, eq 9). To the best of our knowledge, the AZTderived 1,2,3-triazoles have never been synthesized using such a low amount of Cu I catalyst under ambient conditions in water. This successful attempt not only opens the way to efficiently synthesize clean AZT-derived 1,2,3-triazoles for drug design (especially for anti-HIV) but also contributes to the development of new classes of potential biological tracers/labels for various applications. was stirred at room temperature for 30 min under N 2 . Sodium ascorbate (NaAsc, 10 equiv per Cu 2+ ) solubilized in 2 mL of degassed water was added dropwise to the solution of Cu 2+ -L. After the mixture was stirred for another 30 min under N 2 , the Cu I -L solution was ready for use. The details of the syntheses of these catalysts are described in the Supporting Information.

General Procedure for the CuAAC Reactions. A glass vessel equipped with a magnetic stir bar was charged with 0.1 mmol of organic azide and 0.105 mmol of alkyne under a nitrogen atmosphere. Catalytic amounts of catalyst were placed in the vessel under N 2 , and degassed water was added in order to obtain 1 mL as the total volume of water. The reaction mixture was stirred for 20 h at 35 °C under N 2 . After the reaction, the mixture was filtered and then extracted using CH 2 Cl 2 (3 × 10 mL). The organic layer was dried over Na 2 SO 4 and filtered, and the solvent was removed in vacuo to give the corresponding 1,2,3-triazoles. The product was then purified by silica chromatography when necessary.

■ ASSOCIATED CONTENT

* S Supporting Information

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.6b01389.

General data, syntheses and characterizations of the catalysts, detailed experimental procedures for CuAAC reactions and their recycling, and spectra for all compounds (PDF)

■ AUTHOR INFORMATION

Corresponding Author *E-mail for D.A.: didier.astruc@u-bordeaux.fr.

Notes

The authors declare no competing financial interest. tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol and chlorinated mPEG2000 (Figure 2).

■ ACKNOWLEDGMENTS

The ligand has been fully characterized by 1 H NMR, 13 C NMR, MS, elemental analysis and IR. We compared the efficiencies of amphiphilic ligand-transition metal nanoparticles nanocatalysts in the 4-NP reduction reaction (Table 1). We selected the most efficient four NPs, namely AuNPs, PdNPs, RuNPs, and CuNPs. The later three were then utilized for their well-known reactions such as the Suzuki-Miyaura reaction, transfer hydrogenation and "click" reaction, respectively. TMNP-2 Amount [a] [mol%] D core [b] [nm] t 0 [c] [s]

k app [d] [10 -3 s -1 ]

k 1 [e]
[L s - 5), leading to a TON of 2300 and TOF of 96 h -1 . Recycling this catalyst with 0.1 mol % RuNP-2 provides a product yield of 85% or more up to the 3 rd successive recycling run (Table 3). CuNP tested as catalyst for click reaction between benzyl azide and phenylacetylene (Scheme 5 and Figure 6), and found to be extremely efficient. This reaction is indeed quantitatively achieved at 35℃ for 24 h using only 20 ppm of Cu from CuNP-2 leading to an exceptional TON of 28000 and TOF of 1170 h -1 ; this is one of the very best results ever obtained using CuNP catalysts. Moreover, recycling experiments using 100 pm of CuNP provided yields larger than 80% during at least four successive recycling experiments, showing the good stability of the catalyst (Table 4). a Reaction for 48 h.

We used X-ray photoelectron spectroscopy (XPS) to investigate the actually active species in this "click" reaction, and found that the catalyst was in its classic Cu(I) state. It is unavoidable that the CuNPs surface is oxidized by molecular oxygen from air, and the active Cu I species is thus formed in the native oxide layer on the Cu surface through comproportionation of Cu 0 and Cu II , even if caution is taken to remove air.

Further study has then been shown that the weak surface ligand coordination and easy ligand substitution by substrates played a critical role in determining the high efficiencies of the nanocatalysts (Figure 7).

From Mono-to Tris-1,2,3-triazole-Stabilized Gold Nanoparticles and their

Compared Catalytic Efficiency in 4-Nitrophenol Reduction

In this paper, we compared the stabilization of AuNPs by mono-, bis-, and tris-trz and their influence of the trz denticity on the 4-NP reduction by NaBH 4 in water also including comparison with current polyethylene glycol 2000 (PEG) and polyvinylpyrrolidone (PVP) AuNP stabilizers (Figure 8 and Table 5). The synthesis of 1,3-di(1H-1,2,3-triazol-1-yl)propane, 2, followed the published procedures (Scheme 6). Briefly, A dried flask was charged with 1,3-diazidopropane (850 mg, 1 equiv.) and ethynyltrimethylsilane (1.65 g, 2.5 equiv.) in the presence of THF under N 2 . An aqueous solution of CuSO 4 (0.2 equiv., 10 mol% per branch) was added, and stirred for 30 min. Afterward, NaAsc (10 equiv. per branch) was added drop wised. The mixture was then allowed to stir for 24 h at rt. Then, the mixture was then filtered, washed and the solvents were removed in vacuo. Then MeOH and K 2 CO 3 were added, and the mixture was stirred for 24 h at rt to yield a white solid product. This product is characterized by 1 H NMR (Figure 9). On the other hand, the synthesis of the 1,2,3-triazole-mPEG ligand, 3: trimethylsilyl azide (0.2 mL, 1.5 mmol) was added to a mixed DMF/MeOH solution (3 mL, 9:1) that contained the catalyst CuI (5.8 mg, 0.03 mmol) and ethynyl-mPEG (1000 mg, 1 mmol) under N 2 . The reaction mixture was stirred at 90 °C overnight. Then the mixture was cooled to rt, filtered, and the solvents were removed in vacuo. Then, the residue was dissolved in CH 2 Cl 2 and washed three times with water. The organic phase was collected and dried over anhydrous sodium sulfate to yield the white solid product.

The synthesis of AuNP-L was used the gold precursor (1 equiv.) in 1 mL water was added to a solution that contained 1 or 3 equiv. ligand (1 or 3 triazole per Au) in 5 mL water. The mixture was allowed to stir for 15 min. Then, a freshly prepared aqueous solution of NaBH 4 (10 equiv.) was added to the solution dropwise, and the solution was continuously stirred for another 30 min. Dialysis was conducted for 24 hours to remove the excess of ligand and NaBH 4 . The AuNP-L was kept in aqueous solution for characterization and used as catalyst. The AuNPs stabilized by PEG were prepared under identical conditions, except that 1 equiv. PEG per equiv. Au 3+ was used. With this ligand, on the other band, we also showed the influence of AuNP precursors (gold(I)chloro(tetrahydrothiophene) [AuCl(SC 4 H 8 )]) for both AuNP morphologies and catalytic efficiencies. The direct synthesis of Au(I)-ligand complex was not stable, however, and it soon decomposed, resulting in the formation of AuNPs with a relative large SPB (556 nm) and NP size (Figure 10 amd Table 5). On the other hand, 4-NP reduction was very successful, leading to a surprising value of k app =17.5×10 -3 s -1 .

(×10 -3 S -1 ) AuNP-1 b -- (--) -- 0 5.2 (3.5

Design and applications of an efficient amphiphilic "click" Cu I catalyst in water

As mentioned above, CuAAC selectively yielding 1,4-disubstituted 1,2,3-triazoles has been applied to an enormous range of new syntheses and applications to macromolecules and nanomaterial science. The catalytic active Cu I species was usually generated from the cheap and easy available mixture of CuSO 4 and sodium ascorbate (NaAsc), known as the Sharpless-Fokin catalyst. However, the CuAAC reaction rate is low if the catalyst is not present in high concentration and in the presence of activating ligand. For practical reaction processes, in most of the cases the Sharpless-Fokin catalyst is used in relatively large quantities in order to avoid the formation of the 1,5-isomer and to keep an acceptable reaction rate. The problem then remains to remove the copper, which limits this "click" chemistry in electronics and biomedicine. To overcome these difficulties, some ligands have been shown to considerably accelerate the reactions and reduce the catalyst amounts. Based on this tris-trz-PEG amphiphilic ligand, especially benefiting from the chelation effect, new efficient amphiphilic "click" Cu This catalyst shows high activity for CuAAC "click" reaction in water at ambient temperature. Only ppm Cu I were necessary to reach quantitative yields with TON up to 86000 and TOF 3600 h -1 . For the recycling of the catalyst: after the CuAAC reaction, The "click" products from the aqueous solution was extracted using cold diethyl ether (2×5 mL) while keeping the catalyst in the water phase. After charging another run of substrates, the water phase was directly injected by a syringe under N 2 .

External addition of NaAsc (10 equiv) was necessary to ensure keeping the catalytic Cu I species active during catalysis. The amphiphilic tris-trz-PEG ligand is insoluble in cold diethyl ether, allowing the fully recyclability. The catalyst reused at least 6 times without change of ligand structure during the CuAAC reactions. Large-scale syntheses were also successfully achieved with 93 % yield (Table 6). 7). (ii) the amphiphilicity of the tris-trz-PEG ligand containing a tris-triazole tripod that increases the electron density on the metal center;

(iii) a PEG chain allowing homogeneous click reactions in water.

The general procedures of "click" reaction are: a glass vessel equipped with a magnetic stirring bar was charged with 0.1 mmol of organic azide and 0.105 mmol of alkyne under a nitrogen atmosphere. Catalytic amounts of catalyst were added into the vessel under N 2 , and degassed water was added in order to obtain 1 mL as the total volume of water. The reaction mixture was stirred during 20 h at 35 °C under N 2 .

After the reaction, the mixture was filtered and then extracted using CH 2 Cl 2 (3× 10 mL). The organic layer was dried over Na 2 SO 4 and filtered, and the solvent was removed in vacuo to give the corresponding 1,2,3-triazoles. The product was then purified by silica chromatography when necessary. The low level catalyst of PEG-tris-trz-Cu I catalyst showed wide substrates scope in CuAAC reactions between various alkynes and organic azides in water (Figure 12), and excellent yields were generally obtained. Furthermore, the catalyst was applied to the efficient synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties (Figure 13). For instance, 1-ethynylcyclohexanol has a simple structure, and it is known as an active metabolite of the old central nervous system depressant drug ethinamate. The click reaction with benzyl azide in excellent isolated yield (93%) was achieved using only 200 ppm at 35℃ for 20 h.

On the other hand, the PEG-tris-trz-Cu I catalyst also allows click synthesis of 9-ferrocenyltriazole dendrimer and 9-pyridyltriazole dendrimer in excellent yields with 100 ppm Cu per azido branch of catalyst under ambient conditions in water.

Taking the synthesis of 9-ferrocenyltriazole dendrimer as the example: A glass vessel equipped with a magnetic stirring bar was charged with nona-azido precursor (16.69 mg, 1 equiv.) and ethynylferrocene (22.1 mg, 1.05 equiv. per azido group) under argon atmosphere. The PEG-tris-trz-Cu I catalyst (100 ppm per azido group) was added into the vessel under argon, and degassed water was added in order to obtain 1 mL as the total volume of water. The reaction mixture was stirred during 24 h at 40 °C, the light yellow solid formed sticked on the wall of the glass vessel and magnetic stirring bar. After the reaction, the glass vessel was washed twice with water and pentane respectively, and filtered. CH 2 Cl 2 (30 mL) was then added to solubilize the dendrimer, the CH 2 Cl 2 solution was then dried over Na 2 SO 4 and filtered, and the solvent was removed in vacuo to yield the dendrimer. Thus, in this study, the family of nitrogen based ligands that accelerate the CuAAC reactions has been extended with the utilization of the amphiphilic tris-trz-PEG ligand.

This recyclable ligand has now been shown to promote the conventional Sharpless-Fokin catalyst as a highly efficient Cu I "click" catalyst in water for various organic syntheses. Comparative catalytic studies indicate that the tris-trz-PEG ligand is more efficient than the mono-trz-PEG ligand, and reduction of Cu II to Cu I is considerably slower with the former ligand than with later. These trends confirm the favorable effect of the chelation in tris-trz-PEG concerning the catalytic properties.

Introduction

This chapter concerns our approaches of the design of efficient nanocatalysts using graphene-based supports. J Mater Sci

Chemical routes to materials regulates the selectivity. The resulting synergistic effect allows tuning the average binding energy of the NBNP surface and optimizes the charge density at specific active surface metal sites [20,21]. As a consequence, NBNP catalysts are often more active than their monometallic counterparts, and the total catalytic amount of these very efficient NBNP catalysts is therefore minimized for practical applications. In this way, cost-effective catalysts are afforded via dilution of the efficient noble metals with other abundant metals. Rhodium (Rh) has been reported as an efficient catalyst source in a wide range of processes [22], but it is scarce in earth and very expensive, while Ag is much more abundant and much less expensive than Rh. Ag is not industrially very useful in pure bulk form, and it is not a very efficient catalyst in its NP form, however. The blending of Rh and Ag NPs in bimetallic systems has thus been considered as a powerful means to further improve catalytic properties and at the same time to reduce the total amount of Rh. A difficulty along this line is that the construction of Rh/Ag bimetallic systems is not straightforward, due to the well-known immiscibility of these two metals. Indeed even at 2000 °C, the mixture of Ag and Rh does not produce a homogeneous solution, but only segregated clusters emerge out upon cooling. Such a feature has limited the potential applications of Rh/Ag bimetallic systems, and therefore, their chemistry and catalytic behavior have been less studied than those of many other bimetallic systems [23][24][25]. The emergence of nanoscience has brought about the possibility to overcome these problems by reducing the NP size to a very few nm, and small NPs have shown very different properties compared with the bulk form. In particular, the NP size allows solving the problem of the non-spontaneous miscibility [26][27][28][29][30][31]. For instance, recently Pal et al. elegantly established the synthesis of homogeneous Rh/Ag bimetallic NPs by a simple co-reduction process using hydrazine hydrate as reducing agent. Using this reagent, Rh/Ag bimetallic NPs were shown to be a very efficient catalyst for 4-nitrophenol (4-NP) reduction and decomposition of hydrogen peroxide. An ensemble effect was successfully proved by the enhanced catalytic activity that was obtained upon variation of the Ag/Rh ratios [32].

In the present work, we report for the first time the facile synthesis of various RhAg/rGO heterogeneous catalysts (rGO: reduced graphene oxide) with ultrafine NP size and their structural optimization and exceptional catalytic activity. The formation of RhAg bimetallic NPs with very small size (2-3 nm) was ensured using NP encapsulation by the tris(triazolyl)polyethylene glycol (tristrz-PEG) ligand. This procedure allows the effective fixation of the small Rh/Ag NPs onto rGO through the supramolecular H-bonding interactions between the PEG termini of the tristrz-PEG ligand [33][34][35] and surface oxygen functional groups of rGO. The RhAg/rGO heterogeneous catalysts showed exceptional catalytic efficiencies in the 4-NP reduction by NaBH 4 in water at rt. Furthermore, due to the heterogeneity of the catalysts, they were easily recycled, and their long life and high reusability were demonstrated without significant decrease in the catalytic performance up to at least the fifth run.

Experimental section

General data

All solvents and chemicals were used as purchased, unless elsewhere noted. Milli-Q water (18.2 MX) was used for all the NP preparations. Prior to the synthesis, the Schlenk flask was washed with a solution of aqua regia (HCl/HNO 3 = 3:1, v/v) to remove traces of residual metal. UV-Vis absorption spectra were measured with Perkin-Elmer Lambda 19 UV-Vis spectrometer. The inductively coupled plasma optical emission spectroscopy (ICP-AES) analyses are achieved with a Varian ICP-AES 720ES. Transmission electron microscopy (TEM), high-resolution TEM (HRTEM) and scanning transmission electron microscopy (STEM)-coupled quantified energy-dispersive X-ray spectroscopy (EDX) were recorded at LCC, Toulouse. Size was calculated based on at least 100 NPs. X-ray photoelectron spectroscopy (XPS): System SPECS SAGE HR, X-Ray source: Mg Ka nonmonochromatic, operated at 12.5 kV and 250 W. Take off angle was 90°,at*10 -8 Torr. Pass energy for survey spectra is 30 and 15 eV for narrow scans. Analysis: spectra are calibrated to CC carbon 285 eV. Analysis consisted of Shirley background subtraction. Peaks are fitted with symmetrical Gaussian-Lorentzian (GL) line shapes. Sample is dispersed on silica substrate and evaporated prior to measurement.

J Mater Sci

92

Preparation procedures

GO Synthesis

GO was synthesized following a published procedure [36]. In short, 1 g of graphite powder was sonicated and stirred in an ice bath in the presence of 46 mL concentrated H 2 SO 4 (Aldrich 99%) and 1 g of NaNO 3 (Aldrich 99%) for 30 min. Then, 6 g of KMnO 4 (Aldrich 99%) was very slowly added, and sonication was continued for another 30 min, after which the flask was removed and allowed to stir slowly overnight at 30 °C. Next, 50 mL of deionized H 2 O was slowly added under nitrogen followed by 1 h of stirring. Finally, 300 mL of 3% H 2 O 2 (Fisher, 30%) was dispensed into the flask, yielding a yellowish brown GO suspension. The as-prepared suspension was washed several times thoroughly with diluted HCl (3%) and deionized water via centrifugation, until the pH was neutral. After centrifugation, it was then sonicated and thereafter dried in vacuo at 60 °C overnight to obtain a GO powder.

Synthesis of the RhAg/rGO catalysts (Scheme 1)

Catalysts of RhAg/rGO with different molar ratios of Ag and Rh were synthesized in water at rt. Typically, different amounts of AgNO 3 and Rh(NO 3 ) 3 were added in the presence of the tristrz-PEG ligand (the Rh/Ag molar ratio is fixed for 0.002 mmol, and total metal precursors/ligand molar ratio = 1:1) to reach a total of 6 mL aqueous solution, and the mixture was stirred for 15 min. Then, a fresh aqueous solution of NaBH 4 (10 equiv. per total metal precursors, 1 mL) was added into the above mixture with magnetic stirring for 30 min, and GO was added and further stirred for 30 min to obtain uniformity. The mixture was then aged for 3 h, and the solid was separated, washed and dried at 60 °C overnight. yellow color with time, and the progress of the reaction was quickly measured by UV-Vis spectroscopy in a scanning range of 250-500 nm (40 s for each run). For the recycling study, the catalyst was recovered by centrifugation, washed and re-dispersed in water. The reaction was then conducted following the above-mentioned procedure. Control experiments employing the Ag/rGO and Rh/rGO catalysts (0.2 mol% per nitrophenol) were also conducted for comparison.

Catalytic reduction of 4-NP by

Results and discussion

The GO powder was prepared according to a modified Hummer's method [36] followed by sonication treatment, and it was readily dispersed in water to form a light yellow suspension. The TEM image showed that the GO nanosheets consisted of several layered nanostructures (Fig. 1a).

The nanocatalyst construction started with the synthesis of AgNPs in aqueous solution in the presence of tristrz-PEG as the encapsulating ligand and involved reduction of Ag(I) by sodium borohydride [33]. The ligand-stabilized AgNPs presented a surface plasmon band (SPB) at 417 nm, and the AgNPs were monodispersed with a NP size of 2.3 nm.

After the synthesis, GO was directly added to the solution and further stirred for another 30 min, and meanwhile, GO was reduced by excess of NaBH 4 to rGO. The catalyst was then aged for 3 h, washed and dried, yielding the heterogeneous Ag/rGO catalyst (Scheme 1). The deposition process did not change the SPB and the size of AgNPs compared to the initial ligand-encapsulated AgNPs, resulting in the fixation of uniformed, monodispersed AgNPs onto rGO (Fig. S2). ICP-AES analysis indicated that[99% of the AgNPs were deposited onto the rGO.

We assume that the supramolecular H-bonding interactions between the PEG termini of the tristrz-PEG ligand and multiple surface oxygen functional groups, such as -COOH and -OH, of the rGO ensured this quantitative deposition process. The reduction of GO in the presence of a reductant especially in this case the NaBH 4 to rGO is well known, although the surface functional groups are also presented in rGO with some proportions upon reduction. Thus, the residual surface functional groups of rGO ensure this deposition process. The synergy with the triazole groups and PEG of tristrz-PEG ligand that also weekly interacted with the AgNP surface provides the effectiveness of small AgNP stabilization [33,37] (Scheme 1). Rh/rGO was then prepared using the same method. The TEM image shows that the size of the RhNPs is 2.2 nm (Fig. S3).

We then further synthesized RhAg/rGO by dilution of Rh with Ag that changed the Rh to Ag molar ratios, with the aim to further increase the reaction efficiency and to reduce the total catalytic amount. Previously, we have shown that the tristrz-PEG ligand stabilized various transition metal NPs (TMNPs) with ultrafine sizes, which was attributed to the synergy between weak, but multidentate, surface coordination and the overall large bulk of the tristrz-PEG ligand [33]. Moreover, the surface weak ligand coordination and easy ligand substitution by substrates also benefit to the catalysts on the TMNPs surface. Now the utilization of this ligand has been extended to the synthesis of ultrafine NBNPs. With these various heterogeneous catalysts RhAg/rGO in hand, we first used UV-Vis spectroscopy to characterize the Rh/Ag bimetallic NPs (Fig. S1). Among all the samples, RhAg 0.5 /rGO and RhAg 1 /rGO represented the same and smallest SPB of 407 nm, while other samples showed larger SPB absorption wavelengths (Table 1). ICP-AES analysis indicates that, for instance in the RhAg 0.5 /rGO catalyst, [99% of the RhAg NPs are deposited onto the rGO. Figures S4-S8 then show the representative TEM images of the synthesized catalysts RhAg/rGO with different Rh to Ag molar ratios. As shown in the TEM pictures, it is striking that monodispersed RhAg NPs are homogeneously dispersed on the surfaces of rGO. According to the results of the NP size distribution histogram, the average size of RhAg NP is in the range 2.2-3.0 nm (Table 1). The smallest size of RhAg NPs is observed with the RhAg 0.5 /rGO sample, which is only 2.2 nm (Fig. 1b). Interestingly, we observe the formation of ''particle on particle'' by HRTEM and STEM dark-field image (Fig. 1c, and Figs. S9-S11). This might indicate that RhNPs are selectively linked to AgNPs, which may also suggest the formation of new active sites at the RhAg interface, and probably are beneficial for the catalytic reaction. On the other hand, a representative HRTEM image of alloyed RhAg 0.5 NPs also shows the (111) lattice fringe distance of 0.274 nm (Fig. 1d), indicating an increase of the interatomic separation distance for alloyed RhAg NPs. Although we have successfully shown the formation of bimetallic RhAg NPs by TEM, HRTEM and STEM, it is still difficult to obtain homogeneous alloyed RhAg NPs using this ligand encapsulation followed by NaBH 4 reduction method.

EDX analysis was conducted in order to investigate the elemental composition of the RhAg NPs, and the results are represented in Fig. S11 showing Rh, Ag, C and O signals that are provided by the RhAg 0.5 /rGO sample. ICP-AES confirmed that the composition of the metals in this sample was associated with the Rh/ Ag molar ratio of 2:1. For further characterization of the sample, high-resolution scanning transmission electron microscopy-coupled quantified energy-dispersive X-ray spectroscopy (HRSTEM-EDX) mapping of the RhAg 0.5 /rGO sample was investigated (Fig. S12). Upon looking at the compositional maps of Rh, Ag, C and O, the presence of the RhAg NPs is clearly distinguished with the colors and the homogeneously monodispersed points. The exact oxidation states of the constituent metals in RhAg 0.5 /rGO catalyst were checked by X-ray photoelectron spectroscopy (XPS). The Ag 3d core level XPS spectrum of the RhAg 0.5 /rGO catalyst is shown in Fig. 2a. The Ag 3d 5/2 and Ag 3d 3/2 peaks confirm the binding energy (B. E.) values of 368.2 and 374.1 eV, respectively, with a difference of 5.9 eV that is assigned to the metallic state of Ag(0) in the RhAg 0.5 /rGO system. Rh is partially oxidized, however, as the peaks at 308.8 and 313.3 eV correspond to 3d 5/2 and 3d 3/2 of Rh-O, respectively, whereas B. E. values at 306.7 and 311.4 eV are assigned to Rh 3d 5/2 and Rh 3d 3/2 of Rh(0), respectively (Fig. 2b). The surface oxide layers of Rh NPs play a critical role in determining the catalytic activity of metal catalysts [38,39]. This partial oxidation is explained by the ultrasmall NPs size (2.2 nm) and the molar free energy of formation of metal oxides (-2.68 vs.

-39 kcal mol -1 for Ag 2 O and Rh 2 O 3 , respectively) [40]. These factors render the RhNPs relatively easily oxidizable. On the other hand, the higher ionization potential of Ag (7.56 eV) than that of Rh (7.46 eV) and the larger electronegativity of Rh (2.2) than that of Ag (1.9) also account for preventing complete Rh oxidation [32]. Thus, the oxidation of Ag in the catalyst RhAg 0.5 /rGO was not observed, while Rh is partially oxidized, as authenticated by XPS analysis.

Catalytic properties of AgRh/rGO

The catalytic properties of these RhAg/rGO catalysts are explored here in the 4-NP reduction to 4-aminophenol (4-AP) by NaBH 4 , a classic reaction for the scrutiny of the catalytic properties of transition metal NPs [41][42][43][44][45][46][47][48][49][50][51][52][53]. We first establish an energysaving and environmentally friendly way, that is, the 4-NP reduction is conducted at 20 °C in water, instead of high temperature and/or organic solvents (See ''Experimental'' section). The 4-NP reduction by NaBH 4 to 4-AP was pioneered by Pal et al. in 2001, and detailed kinetic studies by Ballauff's group convincingly suggested the mechanism involving rearrangement of the substrate at the NP surface fitting the Langmuir-Hinshelwood (LH) model with an induction time caused by dynamic restructuring of the NP surface [45][46][47][48][49][50][51][52][53]. The 4-NP reduction reaction was easily monitored by UV-Vis spectroscopy using the intensity of the absorption band at 400 nm that corresponds to the decrease of the concentration (C t ) of the nitrophenolate anion with time along with the growth of a weak 4-AP band at 300 nm. C 0 is the initial 4-NP absorption. In the presence of the catalyst, this reaction is fitted with a pseudo-first-order kinetics with respect to 4-NP in the presence of excess NaBH 4 , leading to the determination of the apparent kinetic rate constant, k app =-ln(C t /C 0 )/t, based on the regression of the slope from the logarithm plot [42][43][44]54].

We first used the tristrz-PEG ligand-stabilized AgNPs to catalyze 4-NP reduction. The catalysis of the 4-NP reduction reaction by such AgNPs was not successful using only 0.2 mol% of catalyst, however, and with this catalyst, the reduction did not proceed even up to the tenth runs. Moreover, although we employed AgNPs with 2 mol% per 4-NP, induction time was observed with poor efficiency [33]. On the other hand, in the presence of Ag/rGO as catalyst, the reduction of the 4-NP occurred using the same amount of Ag/rGO catalyst (0.2 mol%) without induction time, with a reaction rate k app = 1.43 9 10 -3 s -1 . The observed enhanced activity and the absence of induction time with the Ag/rGO catalyst are attributed to both the enhanced catalyst robustness and to the two-dimensional (2D) structure of rGO that facilitates 4-NP adsorption by p-p stacking interactions [55]. The 4-NP concentration near the Ag/rGO catalyst is optimized on the rGO surface, which accelerates the reduction process. The Rh/rGO (0.2 mol%) catalyzed reduction of 4-NP also proceeds readily without induction time, with an apparent rate constant k app = 6.1 9 10 -3 s -1 . A control experiment was also conducted in the presence of only GO as the catalyst, and reduction did not proceed even after 50 min.

Figures S13-S19 show the absorbance versus wavelength plots at different times for the reduction of 4-NP to 4-AP in the presence of the different catalysts RhAg 0.25 /rGO, RhAg 0.5 /rGO, RhAg 1 /rGO, RhAg 2 /rGO and RhAg 4 /rGO, respectively. The absorbance peak at 400 nm disappeared faster after adding any of these bimetallic RhAg/rGO catalysts than with the mononuclear catalyst Rh/rGO, indicating a faster reaction activity of the bimetallic catalyst than their monometallic counterparts. As shown in Table 1, all the bimetallic catalysts RhAg NPs showed faster reaction rates than the monometallic NP catalysts, suggesting a favorable synergistic effect between Rh and Ag in the NPs. The so-called ensemble effect should be taken into account concerning the higher activities that have been observed among all the bimetallic RhAg systems. In these bimetallic catalysts, the surface Rh atoms are diluted by the surface Ag atoms, which cause charge redistribution and stabilization of the sole Rh atoms by Ag atoms, resulting in the isolation of more efficient catalyst sites [24,32,40]. The small Rh-Ag NP size and the Rh-Ag interfaces also generate other new active sites for the 4-NP reduction reaction. These factors result in the enhanced catalytic performance of bimetallic RhAg/rGO system compared to monometallic counterparts. For instance, blending Rh with 50% of Ag (RhAg 0.5 /rGO) significantly enhances the reaction activity, k app being 2.4 and 10.3 times larger than those of Rh/rGO and Ag/rGO counterparts, respectively. Among all the RhAg/rGO catalysts, RhAg 0.5 /rGO showed the highest reaction rate, which is also associated with the smallest bimetallic RhAg NPs and SPB. Furthermore, the same catalyst RhAg 0.5 /rGO synthesized under identical conditions in the absence of the tristrz-PEG ligand showed poor activity in 4-NP reduction (k app= 1.17 9 10 -2 s -1 ). This comparison highlighted the critical role of the tristrz-PEG ligand, as already demonstrated in a previous study [33]. Finally, the normalized rate constant (k nor ) that is associated with the amount of catalyst (k nor = k app /m) was also determined. The k app value is very sensitive to various parameters, such as the concentrations of 4-NP and BH 4 - [43,46,49]. This normalized rate constant (k nor )i s generally used for the comparisons of the catalytic efficiency of 4-NP reduction using various heterogeneous catalysts, because the amount of catalyst is involved in the calculation.

The catalytic efficiencies of RhAg/rGO systems (Table 1) are advantageously compared with various recent studies from the literature listed in Table 2,a [59] and AuPt@Au NCs/rGO (k nor = 213 s -1 g -1 ) reported by Feng's group [60]. Therefore, in comparison the catalytic efficiency of the present RhAg/rGO catalytic system is most remarkable.

Based on these results, the mechanism for the 4-NP reduction by NaBH 4 i nthepresenceofRhAg/ rGO catalysts follows earlier suggestions involving BH 4

-adsorption onto the catalyst surface and transfer of active hydrogen species to the NP surface to form surface metal-hydride species [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]59]. In addition, the presence of rGO mediates this process by increasing 4-NP absorption at the RhAg NP surface [55], and the RhAg NP surface is coordinated to the weak tristrz-PEG ligand that is readily substituted by substrates [33]. Consequently, the electronrich Rh atom-coordinated hydrogen species is transferred to the nitro groups at the NP surface. Charge transfer within the Rh-Ag surface toward the Rh sites favors the hydride transfer to this substrate [60,68]. It is also possible that excess BH 4 transfers electrons [69,70] to the bimetallic catalyst surface, still increasing the charge on the key active Rh-H site (Scheme 2).

The reusability of the RhAg 0.5 /rGO catalyst was also investigated. As shown in Fig. 3a, the RhAg 0.5 / rGO catalyst is reused at least five times without significant loss of reaction activity. In the fifth run, the rate constant for the 4-NP reaction was still k app = 12.1 9 10 -3 s -1 , suggesting that the RhAg 0.5 / rGO catalyst exhibits very good reusability in the reduction of 4-NP. This efficiency is also superior to that encountered in most of the cases using noble metal-based NP catalysts. Decreasing the total catalyst amount to an acceptable level with good reaction activity was also attempted. As shown in Fig. 3b, with 0.05 and 0.01 mol% RhAg 0.5 /rGO catalyst, the reaction rate is k app = 8.2 9 10 -3 s -1 (k nor = 3140 s -1 g -1 ) and k app = 5.3 9 10 -3 s -1 (k nor = 10140 s -1 g -1 ), respectively, demonstrating the success ful design of cost-effective RhAg/rGO catalytic system.

Scheme 2 Proposed mechanism for the 4-NP reduction by NaBH 4 in the presence of a RhAg/rGO catalyst.

J Mater Sci

Conclusions

The facile synthesis of the heterogeneous catalyst RhAg/rGO with very narrow bimetallic RhAg NP size distribution and the exceptional catalyst activity for 4-NP reduction has been developed here for the first time. The presence of the tristrz-PEG ligand not only ensures ultrafine bimetallic NP formation, but also allows quantitative fixation of the RhAg NP onto the rGO surface. The bimetallic RhAg NPs involve a synergy between the two metals on rGO that improves the catalytic activity compared to both monometallic counterparts. Moreover, the catalyst exhibits very good reusability, and the catalyst amounts are largely decreased with high efficiency. The present work not only sheds a new light on the development of highperformance bimetallic NPs using appropriate supporting materials [71,72], but also contributes to the design of very efficient, cost-effective catalysts for various current organic reactions. Fe 2p spectrum, which correspond to the Fe 2p 1/2 and Fe 2p 3/2 core levels of a-Fe 2 O 3 , respectively. 9 Moreover, the shakeup satellite peak at about 719.0 eV, 10 a characteristic of the Fe 3+ species, is also clearly seen.

Catalytic applications of the new catalyst 1 were first probed for the 4-NP reduction by NaBH 4 in water, 11 a trusted test reaction pioneered by Pal's group 11a to explore the catalytic efficiency of nanoparticles surfaces. Indeed this reaction hardly proceeds in the absence of a metal catalyst. 11 In the presence of catalyst 1 in an aqueous solution containing 4-NP (1 equiv.) and NaBH 4 (81 equiv.), reduction proceeds with an induction time (t 0 )o f 1160 s (Fig. 2). This feature suggests the required activation and dynamic restructuring of the a-Fe 2 O 3 nanocluster surface, as shown by Ballauff's group using AuNP and PdNP catalysts. 11d,g,h Following the induction time, 4-NP reduction proceeds very well, with an apparent kinetic rate constant (k app )o f4 . 1 7Â 10 À4 s À1 (Fig. S3, ESI †). Given the addition of such a low amount of catalyst 1 (150 ppm per 4-NP), its catalytic efficiency is remarkable and even superior to the best noble metal nanoparticle catalysts.

Control experiments conducted in the presence of GO alone i n d i c a t e dt h a tt h er e a c t i o nd i dn o tp r o c e e da ta l l .

High-resolution UV-vis spectroscopy was used to monitor the reaction process by mixing a-Fe 2 O 3 /GO and NaBH 4 (Fig. S3 bottom, ESI †). The spectra did not change during the reaction, and no peaks at 352 nm and at 262 nm that corresponded to Fe(0) were observed, suggesting that Fe(0) is not involved in the reaction. To address the iron-leaching problem, we have conducted 4-NP reduction after the removal of the a-Fe 2 O 3 /GO catalyst by simple filtration. The yellow color of the reaction mixture did not change during 2 days, and the hot filtration test was negative (vide infra), suggesting that leaching of soluble Fe(0) species does not account for the reaction mechanism. It cannot be excluded that tiny amounts of Fe(0) are formed, however, and serve as a catalyst. 12 Encouraged by the remarkable efficiency of 1 obtained in the 4-NP reaction, the catalytic performances have been further investigated in the Suzuki-Miyaura coupling reaction between bromobenzene and phenylboronic acid. This reaction was conducted at 80 1C under a nitrogen atmosphere for 24 h in the presence of 150 ppm mol% catalyst and K 2 CO 3 as the base. Optimizations of the SM coupling reaction were first conducted by leaving the solvent as the only parameter. Solvent mixtures containing water and, as a co-solvent, DMF, ethylene glycol or EtOH were tested for this model reaction. The results showed that the presence of the H 2 O/EtOH solution led to the best catalytic performance with a quantitative conversion and an 87% isolated yield. The amount of solvent is crucial in this SM reaction, as a larger amount of H 2 O/EtOH solvent leads to a lack of conversion, while low amounts of solvent allow the reaction to proceed well (ESI †). These results indicate that the concentration of the substrates is crucial for this reaction. 1d XPS was used to characterize the Fe oxidation state after the SM reaction, but no Fe(0) was found, indicating that EtOH does not reduce a-Fe 2 O 3 under the present conditions (Fig. S12, ESI †).

In order to identify the actual active phase, ICP-AES analysis was conducted to exclude the possibility of trace Pd residues in 1, because ppm levels of Pd are known to be sufficient for the catalysis of SM reactions. ICP-AES analysis showed that there was no residual Pd (or below the detection limit of 0.5 ppm) in 1. Control experiments have also been conducted using either GO or a-Fe 2 O 3 as the tentative catalyst for this model SM reaction, and no reaction occurred under these conditions. To investigate the homo-or heterogeneity of the a-Fe 2 O 3 nanocluster/GO system, a hot filtration test was conducted. The standard SM reaction between bromobenzene and phenylboronic acid proceeds well in the presence of the catalyst, whereas the removal of the catalyst at half way inhibited the continuationofthereaction(Fig. S13,ESI †). Thus, the SM reaction by a-Fe 2 O 3 /GO occurs heterogeneously. It was also conducted in the presence of a-Fe 2 O 3 /active carbon for comparison, and this reaction occurred with poor yield (23%). Thus, it is concluded that 1 catalyzes the SM reaction, and the presence of GO enhances the catalyst efficiency. The high surface area of the GO support increases the concentration of substrates near the a-Fe 2 O 3 catalyst and its efficiency. 13 Given the optimized reaction conditions and high efficiency of catalyst 1, the scope of the SM coupling reaction was examined with 1 (150 ppm) in a mixture of EtOH and H 2 O under nitrogen atmosphere at 80 1C within 24 h (Table 1). A series of bromobenzene derivatives bearing various substituents were tested for the SM coupling reactions with phenylboronic acid under the optimized conditions.

Bromobenzene derivatives containing electron-withdrawing (NO 2 , CHO, CH 3 CO) and electron-donating (NH 2 , CHO, CH 3 ) groups in the para position were suitable coupling partners, and the corresponding coupling products were all efficiently isolated with good yields (Table 1). No direct relationship between the yields and the electronic nature of the bromobenzene substituents was found, however. Substituted arylboronic acids were also investigated, and they reacted smoothly with bromobenzene to provide the desired products in good yields (entries 8 and 9). Comparison of catalyst 1 used in the present study with various available Pd catalysts for the SM reaction in aqueous solution from the literature (Table S1, ESI †) shows the advantages of the utilization of catalyst 1. No coupling was obtained between bromobenzene and n-butylboronic acid, 1-bromopentane and phenylboronic acid, or 1-bromopentane and n-butylboronic acid, however.

The recyclability, a key issue in heterogeneous catalysis from both practical and environmental points of view, was also examined herein using a biphasic method. After the first reaction, diethyl

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ether was added to extract the product while keeping the catalyst in the aqueous phase, followed by the charge of another run of substrates. In this way, the ppm amount of catalyst 1 for the SM coupling reactions was successfully recycled four times (ESI †), and therefore it is concluded that 1 is an excellent heterogeneous catalyst for the SM coupling reactions.

In conclusion, the heterogeneous system 1 is shown here to behave as a remarkable catalyst for both 4-NP reduction and Suzuki-Miyaura coupling reactions in aqueous solvents with only parts-per-million catalyst loading.Thepresenceofthetris-trz-PEG ligand not only ensured the formation of a-Fe 2 O 3 but also the quantitative deposition of a-Fe 2 O 3 onto GO induced by supramolecular interactions. Moreover, recycling of the catalyst was also shown to be excellent. The mechanism of catalytic activation by a-Fe 2 O 3 /GO remains unclear in these two reactions, especially since no Fe(0) was detected. Also note that the lack of extension of the Suzuki-Miyaura reaction to alkyl bromides and alkylboronic acids is a limitation that must be taken into account in the mechanistic investigation of such catalytic systems.

Overall, the principles and results presented herein should significantly contribute to the development of ''green chemistry'' applications involving earth-abundant metal heterogeneous catalysts.

Financial support from the China Scholarship Council (CSC) of the People's Republic of China (grant to C. W.), the Universities of Bordeaux, Toulouse 3, the LCC (Toulouse), and the Centre National de la Recherche Scientifique (CNRS) is gratefully acknowledged.

Notes and references

Redox Synthesis and high catalytic efficiency of transition-metal nanoparticle-graphene oxide nanocomposites

Changlong Wang, Roberto Ciganda, Luis Yate, Jimena Tuninetti, Victoria Shalabaeva, Lionel Salmon, Sergio Moya, Jaime Ruiz, Didier Astruc *

Dedication ((optional))

Abstract: Although nanocatalysis is a promising area, increased efficiency and greenness are actively sought. Here we report the principle of the syntheses of graphene oxide (GO)-supported metal nanocatalysts (MNPs) for a variety of transition metals including both noble metals and biometal using either exergonic or endergonic redox reactions between GO and the transition metal salts. These new nanocatalysts are highly efficient in water at ambient temperature for 4-nitrophenol reduction (the test reaction), Sonogashira coupling, azide-alkyne 1,3-cycloaddition (click reaction) and dihydrogen production upon hydrolysis of ammonia-borane and recyclable.

Nanocatalysis is a very promising area, [1] because high performance nanoparticles (NPs) may be efficiently designed in the absence of ligands that are often toxic, expensive, sensitive and/or of timeconsuming synthesis. A variety of organic and inorganic nanocatalyst stabilizers have also been reported, but they usually damage the catalytic activity and may be difficult to remove. [2] Among heterogeneous catalyst supports, carbon materials have proven remarkable because of possible synergetic catalytic activation. [3] Carbon-supported NPs are usually obtained by metal cation reduction using various reductants, but catalysis may be marred by the reactant residue on the NP surface. Clean direct metal cation reduction by carbon materials has rarely been reported, however. Recently Dai's group utilized single-walled carbon nanotubes (SWNT) sidewall as reductant and stabilizer. [4] Redox-mediated nanocatalyst synthesis has also been demonstrated by Chen's group and Tang's group who utilized graphene oxide (GO) and reduced GO as redox mediator to provide efficient noble metal nanocatalysts with Pd and Au respectively. [5] Here we report the general redox synthesis of green graphene-oxidesupported transition metal nanoparticle catalysts as a clean and most useful synthetic method of NP/GO catalyst avoiding the use of external reductant. This method applies here from noble metals for which the electron transfer from GO is exergonic, thus favorable, to first-raw biometals for which this redox process is endergonic but nevertheless accomplished owing to the fast follow-up NP formation. This concept is also extended to bimetallic NP-graphene oxide composites that include a noble metal and a biometal. It is very efficiently applied here to a variety of reactions in water at room temperature (rt) with remarkably low amounts of catalytic metals including 4-nitrophenol reduction (a reaction used as a test to optimize catalyst preparations), Sonogashira coupling, azide-alkyne 1,3-cycloaddition (click reaction) and dihydrogen production upon hydrolysis of ammonia-borane.

Rh NPs have not so far been generated by redox mediation with GO, but the oxidation potential of GO (0.48 V vs. SCE) [5a] and the redox potential of Rh 3+ /Rh (0.76 V vs. SCE), [6] should in principle allow an exergonic primary electron transfer between GO and Rh 3+ . Thus the redox-mediated synthesis of GO-stabilized RhNPs should be applicable for the production of a clean Rh-based nanocatalyst as our present results demonstrate. First, GO was synthesized from commercial graphite using the modified Hummers method, [7] and transmission electron microscopy (TEM) images showed layered and flat structures (Figure S1), then sonication, and stirring formed a GO dispersion. Let us take the synthesis of RhNPs/GO nanocatalyst as the first example. RhNPs/GO was prepared by dropwise addition of an aqueous solution of RhCl3 to the GO dispersion by syringe at 0°C followed by further stirring for another 30 min (SI). UV-vis. spectroscopy was used to monitor the reduction process with the rhodium d-d transition absorbance at 379 nm and 480 nm gradually decreasing with time, verifying the reduction of Rh 3+ to Rh(0) by GO. [8] The reduction process was faster upon increasing the temperature. For instance the reduction of Rh 3+ to Rh(0) by GO at 45℃ took only 1 min, whereas at 0℃ it required 30 min (Figure S4). The observed enhanced efficiency in the synthesis is attributed to an instantaneous nucleation process upon increasing the reaction temperature, resulting in reduced RhNP size (Table S1). Ostwald ripening takes place at higher temperature (> 45℃) following Rh atom nucleation, however, leading to the decrease in the number of Rh nuclei and to RhNP overgrowth. [6] Moreover after collecting by centrifugation, washing and redispersion in water, the nanocatalyst underwent a darker-to-lighter color change with increased temperatures, which is presumably related to the changes of RhNP size (Figure S5). Taken together, these phenomena indicate that the choice of the appropriate temperature in the synthesis optimizes the interaction between the RhNPs and the GO, a higher temperature weakening the GO anchoring ability and increasing the mobility of the Rh nuclei on the GO surface. [ 5,6,9] Figure 1a shows the STEM image of RhNP/GO from the synthesis at 45℃. It is striking that the 1.8±0.3 nm RhNPs are fairly monodisperse on the GO surfaces. A high-resolution TEM (HRTEM) image (Figure 1b) of the RhNPs shows that the interplanar spacing of the particle lattice is 0. decreases during Rh 3+ reduction (Figure 1d). [5a] The reducing nature of GO is due to the oxygenated functional groups attached to the hexagonal basal plane, further suggesting that these oxygenated functional groups (e.g. -OH, -COOH, epoxy) on the GO nanosheets play an important role of nanoparticles stabilizing ligands with the lone pairs of the oxygen atoms in the formation of RhNPs. [9] The B. E. values at 307.6 and 312.8 eV are assigned to Rh 3d5/2 and Rh 3d3/2 of Rh(0) respectively, [10] indicating the presence of metallic Rh (Figure S10). A ca.1 eV red shift of XPS peak of these very small RhNPs is observed and compared to bulk Rh, which is typical for very small metal NPs on a variety of support materials and is generally attributed to the reduced core-hole screening in metal clusters.

[5b] Such a sizedependent alteration of electronic structures [5b] is seemingly concomitant with the enhanced catalytic properties (vide infra).

These results indicate that the high density of oxygen atom-containing functional groups on the GO surface interact with Rh atoms and therefore provide stabilization of RhNPs. A similar synthesis conducted under dark and only stirring in order to exclude the influence of light and power caused by the sonication showed no difference in the Rh 3+ reduction to Rh(0) by GO. This confirms that the redox reaction between GO and Rh 3+ accounts for the synthesis of RhNP/GO, as for the reaction proposed by Dai et al. [4] On the other hand, a galvanic reaction-like process in which the Rh reduction occurs on Rh nuclei by electrons transferred from GO may also be involved in the growth of the RhNPs after nucleation, accompanying GO oxidation. [5,11] The Raman spectra of the nanocatalyst RhNP/GO-45℃ showed no obvious change in the intensity ratio of ID/IG compared to pure GO, however (Figure S11), suggesting that the formation of RhNPs does not greatly reduce the size of the in-plane sp 2 domains of graphene. [4] Indeed, the XPS data suggest that the atomic content of Rh is only 1.9 %, which is too low to cause a large structural damage to GO sheets.

The catalysis of reduction by NaBH4 of the pollutant 4-nitrophenol (4-NP) in water (Equation 1) to the useful dye 4-aminophenol was first probed; this is a trusted test reaction to further explore the catalytic efficiency of NP surfaces and optimize catalytic conditions. [12] According to the reaction mechanism (see mechanistic details in the SI), the activation and dynamic restructuring of the NP surface are required, which eventually proceeds with an induction time if NP ligands are present. [13] Therefore, in the absence of surface restructuration if no ligand replacement is required, the 4-NP reduction catalyzed by surface-clean RhNP/GO would proceed with higher efficiency without induction time. The first attempt using 0.05 mol% catalyst in all the cases indicated that reduction was fast (in 40 s, the time for a complete scan) (SI), while control experiment showed the lack of any reactant conversion in the presence of only GO. Further decreasing the catalyst amount to 10 ppm (RhNPs per 4-NP) allows to easily monitor the reaction processes by UV-vis. spectroscopy, showing very fast 4-NP reduction without induction time (Table S1 and section 3).

The catalytic efficiencies were shown to undergo a volcano-type relationship with respect to RhNP/GO nanocatalysts synthesized at various temperatures. The catalyst RhNP/GO-45℃ showed the highest reaction rate, kapp = 11.8×10 -3 s -1 , 1.65 times higher than that of RhNP/GO-0℃. The comparisons shown in Table S2 indicate that this catalyst showed the best efficiency ever obtained among various reported efficient catalysts. Remarkably, upon decreasing the total amount of RhNP/GO-45 ℃ to 1 ppm (RhNPs per 4-NP), high efficiency still remained, with kapp = 4.29×10 -3 s -1 that is 1.4 times higher than the reaction rate obtained with 1 ppm of the catalyst RhNP/GO-0℃ under identical conditions. The remarkable efficiencies with exceptional low (ppm) amount of catalyst have so far never been reported and could be attributed to the ultrafine RhNP size and the very active surface-clean RhNPs. The presence of GO also increased the concentration of substrates near the surface Rh atoms, [14] benefiting to the catalytic efficiency.

With the efficient RhNP/GO-45℃nanocatalyst in hand, we then turned to another valuable reaction: the hydrolysis of ammonia-borane (AB) for H2 generation. Owing to its high hydrogen content (19.6 wt%), high stability in the solid state and solution under ambient conditions, nontoxicity, and high solubility, AB has been considered as one of the leading contender in promising chemical H2-storage materials. [15] Although many catalysts have been designed for the hydrolysis of AB, high-performance noble metal NPs still remain the most active catalysts for this reaction. [16] High catalyst loading of noble-metal catalyst and specific treatments are essential for the practical efficiency and sustainability, however. Herein we scrutinize the use of RhNP/GO-45℃ as a nanocatalyst for the hydrolysis of AB in water under air. This provides one of the highest turnover frequencies (TOFs) for H2 generation near or at ambient temperature with low catalyst amounts.

The reaction profile in the presence of various amounts of RhNP/GO-45℃ is shown in Figure S21. The nearly stoichiometric amounts of hydrogen release (3 equiv. H2 per AB), indicate that hydrolysis of AB catalyzed by RhNP/GO-45℃ proceeds according to Equation (2):

At the beginning of the reaction, the decay of AB producing H2 was fast and linear as a function of the reaction time. Later on, it became slower especially under lower catalyst amounts. The hydrolysis of AB at rt (25±0.5℃) was completed within the shortest time (7.75 min) when the amount of RhNP/GO-45 ℃ was 0.15 mol%, providing a turnover frequency (TOF) of 258 molH2 molcat -1 min -1 . The highest TOF was obtained with the optimum catalytic performance in the presence of 0.1 mol% catalyst for 9.5 min (TOF = 316 molH2 mol cat -1 min -1 ), while a further decrease of catalyst amount led to a longer reaction time and therefore the decrease of TOF values (Table S3). On the other hand, the uncatalyzed thermal reaction in the absence of catalyst showed negligible dehydrogenation of AB at the early stage of the reaction. The catalytic efficiencies obtained herein are comparable to the best previously reported performances achieved using several noble metal-based NP catalysts, showing the high efficiency of the present RhNP/GO system for hydrolysis of AB (Table S4).

Figure S21 demonstrates that the logarithmic plot of the calculated initial reaction rate vs. catalyst concentration has a slope of 1.03, indicating that the hydrolysis of AB catalyzed by RhNP/GO-45 ℃ follows a first-order kinetics with respect to catalyst concentration. The nearly horizontal line (slope of 0.042) indicates that the hydrolysis of AB catalyzed by RhNP/GO-45℃ is zero-order with respect to the AB concentration (Figure S22). This implies that AB activation is easy and thus rules out the possibility that the activation of AB in the ratedetermining step (RDS). Furthermore, the activation energy (Ea) of hydrolysis of AB was determined to be approximately 21.4 kJ/mol (Figure S23 and calculations), one of the lowest Ea values compared to the literature (Table 3). Although the catalytic rates in the hydrolysis of AB catalyzed by RhNP/GO-45 ℃ is independent of the AB concentration, the kinetic isotope effects (KIEs) [17] were further investigated to shed light on the RDS of the reaction. Specifically in the hydrolysis of AB, the KIE value should tell if N-H or B-H or both bonds are broken or not during the RDS. [18-20] The hydrolysis of the deuterated products of AB (see their synthesis in the SI) in the presence of RhNP/GO-45℃ results in slower reaction rates (Figure S27). A KIE of 1.33 was determined for deuteration at the boron site (NH3BD3), which indicates a similar dehydrogenation behavior to that of AB in H2O. This shows the absence of large KIE for hydrolysis of AB deuterated at the boron site (NH3BD3). A larger KIE (2.57) was found for ND3BH3, suggesting that the O-H bond cleavage of H2O might be in the RDS. This would be similar to the metalcatalyzed borohydride hydrolysis, in which half of the hydrogen comes from water. [21] Indeed, H2O is activated by oxidative addition of a O-H bond on noble metal NP surfaces, forming adsorbed -OH and -H species. For instance, well-known precedents are found in the role of PtNPs as redox catalysts in water photo-splitting. [22] On the other hand, since the reaction rate is zero-order with respect to concentration of AB, H2O dissociation alone as the RDS is not possible. Moreover, considering that the energy for the cleavage of the O-H bond in water (~493 kJ mol -1 ) [23a] is higher than those of B-N and B-H bond (~117 and ~430 kJ mol -1 , respectively), [24b] and the low energy barrier (Ea) obtained in the present hydrolysis reaction, the involvement of H2O activation in the RDS of the hydrolysis is energetically favorable. Thus H2O is most likely activated by an indirect O-H bond cleavage to form -H and -OH species promoted by AB in the presence of RhNP/GO-45℃. [19,20] Activation proceeds similarly in H2O activation for NaBH4 hydrolysis. We also suggest that the "hydridic" B-H hydrogen atom of AB forms a hydrogen bond with an "acidic" hydrogen atom of water in the ground state and that this B-H -…H + -O system undergoes oxidative addition followed by H2 elimination on the Rh surface. Based on this understanding and experimental results, the hydrolysis of AB catalyzed by RhNPs/GO-45℃ in water is best presented overall as shown in Figure 2. The B-N bond in the AB is dissociated, since the NH3 group does not participate in the hydrolysis. [16a] On the other hand, the presence of GO facilitates the adsorption of the reactant or desorption of products in water, [14] thus accelerating the overall process and improving the catalytic activity.

The general principle of transition-metal-GO nanocatalysts is extended to the synthesis of AuNPs/GO, PdNPs/GO, CuNPs/GO, and CuPd NPs/GO at 45℃ under identical conditions. In the case of AuNPs/GO, reduction of Au 3+ by GO (Au 3+ /Au 0 = 1.5 V v.s SHE) results in the high efficient AuNPs/GO nanocatalyst with AuNPs of 3.3 nm (Figure S28), as exemplified by the 0.05 mol% AuNPs/GO nanocatalyst catalyzed 4-NP reduction in water (Figure S29) without induction time and remarkable efficiency (kapp = 3.7×10 -3 s -1 ) compared to the recently reported values (Table S2).

Another challenging example is the synthesis of first raw metal NPs by reduction the metal precursors with GO, because the redox potential of M 2+/3+ /M(0) compared to the oxidation potential of GO makes the reaction endergonic. Upon heating at 45℃, however, Cu 2+ reduction (Cu 2+ /Cu 0 =0.34 V vs. SHE) by GO proceeds due to the fast follow-up Cu atom aggregation that shifts the apparently unfavorable redox process. Thus the formation of CuNPs/GO in this way was confirmed by both UV-vis. spectroscopy and XPS. No SPB was observed due to the small CuNP size (3.0 nm), but the surface Cu(0) oxidation state is shown by XPS (Figure S31). On the other hand, 4-NP reduction is successfully achieved using 0.5% mol CuNPs/GO catalyst with no induction time and a high efficiency of 5.2×10 -3 s -1 (kapp). The absence of induction time in the 4-NP reduction suggests that activation and dynamic restructuring of the Cu(0) surface is not necessary due to the absence of molecular ligand. Note that even weakly stabilizing triazole-based ligand on CuNPs provoke the requirement of an induction time for 4-NP reduction. [24] The high efficiency of the CuNPs/GO nanocatalyst was also confirmed by the "click" reaction between benzyl azide and phenylacetylene, in which 93% isolated yield was achieved at 35 ℃ for 24 h using only 0.01 mol% of CuNPs (Equation 3); this is one of the lowest catalyst amounts among recent literature values.

XPS suggests that the active Cu I species is formed in the native oxide layer on the Cu surface through comproportionation of Cu 0 and Cu II (Figure S31).

Pd/Cu nanocatalysts have been successfully applied to Sonogashira coupling reactions, in which two cooperative catalytic cycles of Pd and Cu form the mechanism; thus an increased efficiency of Sonogashira coupling reaction is expected. [25] We assumed that the double reduction of equimolar amount of Pd 2+ (Pd 2+ /Pd 0 =1.5 V v.s SHE) and Cu 2+ by GO could result in a valuable heterogeneous catalyst for Sonogashira coupling reaction under hopefully very favorable conditions. Thus CuPd NPs/GO nanocatalyst prepared in this way was characterized by TEM and XPS. TEM showed the NP size is around 3.5 nm (Figure S35), while XPS suggested the molar ratio is Pd:Cu=1:1. 35. Moreover, the CuPd NPs surface showed both the surface Cu(0) and the Cu 2+ oxidation states of Cu (Figure S36), and the XPS peak 3d5/2 of Pd(0) located at 335.9 eV (Figure S37 and discussions). For comparison, CuNPs/GO and PdNPs/GO nanocatalysts were separately prepared and tested in the Sonogashira coupling between iodobenzene and phenylacetylene in water at room temperature (rt) for 24 h with 0.05 mol% metal loading. PdNPs/GO nanocatalyst with Pd size of 2.8 nm showed an acceptable 85 % conversion, while in the case of Cu NPs/GO nanocatalyst the conversion was less than 20%. Note that the result of PdNP/GO is already very good at rt, but with combined Cu and Pd, remarkably conversion was quantitative with 93% isolated yield in this Sonogashira coupling reaction (Equation 4). Therefore, synergistic CuPd NPs/GO nanocatalyst is an excellent catalyst for Sonogashira coupling in water at rt, i.e. under environmentally-friendly condition.

Finally, the reusability of the catalyst was studied using RhNP/GO-45℃ nanocatalyst in the hydrolysis of AB in water by continuous addition of a new proportion of AB aqueous solution when the previous run was completed. In this way RhNP/GO-45℃ was successfully recycled four times (Figure S40). Therefore it is an excellent catalyst for the hydrolysis reaction. The observed little decrease of activity in the fourth run is probably ascribed to the aggregation of RhNPs as shown by TEM image taken after recycling experiments (Figure S41). It is due to the slight deactivation effect of the hydrolysis product metaborate [15g,16a,16b,26] that accumulates during the hydrolysis and partly inhibits the catalytically active Rh surface atoms, and to the dilution of the reactant in water.

In summary, a simple, clean redox reaction between various transition metal cations and GO has been shown here to lead to the synthesis of ultrafine, surface-clean metal NPs on graphene oxide with good monodispersity. This method avoids the formation of reactant residues inhibiting the catalytic NP surface. The appropriate choice of temperature during the synthesis improves the reduction efficiency and enhances the interaction between the RhNPs and GO. Consequently, the nanocatalyst RhNP/GO without any other ligand shows exceptional efficiency in the 4-NP reduction down to 1 ppm metal level, and it is also very efficient for the hydrolysis of AB to produce H2. The KIE studies allow the clarification of the RDS for AB hydrolysis. Moreover, this strategy also produces other excellent metal NP/GO catalysts for redox reactions in general, showing high efficiency in 4-NP reduction, Sonogashira coupling at rt, click reaction and hydrolysis of AB for hydrogen production with low amounts of catalytic metals. The activation of NP/G by GO as ligand recalls the efficient catalysis using oxides as ligands, [27] although the NP-GO interactions are of different nature here, of rather synergetic supramolecular type. The principles and clean and simple catalytic method presented herein could be extended to other transition-metal nanocatalysts and should contribute to the rational design of efficient nanocatalysts for a large variety of chemical reactions. s -1 (k nor = 3140 s -1 g -1 ) and k app = 5.3 ×10 -3 s -1 (k nor = 10140 s -1 g -1 ), respectively, demonstrating the successful design of cost-effective RhAg/rGO catalytic system (Figure 4). The work not only sheds a new light on the development of high performance bimetallic NPs using appropriate supporting materials, but also contributes to the design of very efficient, cost-effective catalysts for various current organic reactions. XPS showed the core level binding energies located at 726. Furthermore, α-Fe 2 O 3 nanocluster/GO catalysts also showed high efficiency towards Suzuki-Miyaura reaction with only parts per million (ppm) amount of metal loading.

Entry for the

We first optimized the reaction condition by leaving the solvent as the only parameter.

Solvent mixtures containing water and, as co-solvent, DMF, ethylene glycol or EtOH were tested for this model reaction. The results showed that the presence of the H 2 O/EtOH solution led to the best catalytic performance with a quantitative conversion and a 87% isolated yield (Table 2). The procedures for Suzuki-Miyaura coupling reactions are : A dry Schlenk flask was charged with K 2 CO 3 (2 equiv.), phenylboronic acid (1.5 equiv.), and bromobenzene (1 equiv.). The catalyst 1 was then successively added, and the solvents H 2 O and EtOH were added in order to make a total of 2 mL of solvent (volume ratio of H 2 O/EtOH:

1/1). The suspension was then allowed to stir under N 2 for 24 hours at 80℃. After the reaction, the Schlenk flask was cooled to r.t., the mixture was extracted three times with diethyl ether (Et 2 O, 3 × 10 mL), the organic phase was dried over Na 2 SO 4 , and the solvent was removed in vacuo. In parallel, the reaction was checked using TLC in only petroleum ether as eluent. The crude product was checked by 1 H NMR in order to calculate the conversion. The purification by flash chromatography column was conducted with silica gel as the stationary phase and petroleum ether as the mobile phase.

The Suzuki-Miyaura reactions by α-Fe 2 O 3 nanocluster/GO catalyst showed broad substrates scope. Bromobenzene derivatives containing electron-withdrawing (NO 2 , CHO, CH 3 CO) and electron-donating (NH 2 , OCH 3 , CH 3 ) groups in para position were suitable coupling partners, and the corresponding coupling products were all efficiently isolated with good yields (Table 3). In summary, the principles and results presented in this work should significantly contribute developing the ""Green Chemistry" applications involving earth-abundant metal heterogeneous catalysts.

Redox Synthesis and high catalytic efficiency of transition-metal nanoparticle-graphene oxide nanocomposites 123

Nanocatalysis is a very promising area, because high performance nanoparticles (NPs) may be efficiently designed in the absence of ligands that are often toxic, expensive, sensitive and/or of time-consuming synthesis. A variety of organic and inorganic nanocatalyst stabilizers have also been reported, but they usually damage the catalytic activity and may be difficult to remove. Facing this problem, we report highly efficient ligand-free nanocatalysts synthesis based on the redox reaction between transition-metal cations and GO providing transition metal NP/GO nanocatalysts and their use in water under ambient conditions for a variety of reactions.

We generalized the concept of "redox mediated synthesis" on the GO-supported metal nanocatalysts. This means that GO is used as an electron-reservoir nanomaterial that transfers electrons and eventually oxo ligands to the metals of the NPs. This recalls

Basset"s strategies using inorganic oxide materials as ligands of early transition metal-based molecular catalysts, although the binding is considerably stronger in the latter case. Both noble metals and biometals using either exergonic or endergonic redox reactions between GO and the transition metal salts have been used in our general approach.

The general procedure for the synthesis of transition-metal nanoparticle-graphene oxide nanocomposites are (taking the synthesis of RhNP/GO as example, Figure 9): showed the highest reaction rate, k app = 11.8×10 -3 s -1 . Remarkably, upon decreasing the total amount of RhNP/GO-45℃ to 1 ppm (RhNPs per 4-NP), high efficiency still remained, with k app = 4.29×10 -3 s -1 that is 1.4 times higher than the reaction rate obtained with 1 ppm of the catalyst RhNP/GO-0℃ under identical conditions (Figure 11). The remarkable efficiencies with exceptional low (ppm) amount of catalyst have so far never been reported and could be attributed to the ultrafine RhNP size and the very active surface-clean RhNPs. The presence of GO also increased the concentration of substrates near the surface Rh atoms, benefiting to the catalytic efficiency. The efficient RhNP/GO-45℃nanocatalyst was also tested for the hydrolysis of AB for hydrogen generation (Scheme 1). The highest TOF was obtained with the optimum catalytic performance in the presence of 0.1 mol% catalyst for 9.5 min (TOF = 316 mol H2 mol cat -1 min -1 ), showing the high efficiency of the present RhNP/GO system for hydrolysis of AB (Table 4). The logarithmic plot of the calculated initial reaction rate vs. catalyst concentration has a slope of 1.03 (Figure 12a), indicating that the hydrolysis of AB catalyzed by RhNP/GO-45℃ follows a first-order kinetics with respect to catalyst concentration.

The nearly horizontal line (slope of 0.042) indicates that the hydrolysis of AB catalyzed by RhNP/GO-45℃ is zero-order with respect to the AB concentration (Figure 12b). Furthermore, the activation energy (E a ) of hydrolysis of AB was determined to be approximately 21.4 kJ/mol (Figure 12c). hydrolysis. We also suggest that the "hydridic" B-H hydrogen atom of AB forms a hydrogen bond with an "acidic" hydrogen atom of water in the ground state and that this B-H -…H + -O system undergoes oxidative addition followed by H 2 elimination on the Rh surface. The B-N bond in the AB is dissociated, since the NH 3 group does not participate in the hydrolysis (Figure 13). On the other hand, the presence of GO facilitates the adsorption of the reactant or desorption of products in water, thus accelerating the overall process and improving the catalytic activity. The reusability of the catalyst was also studied, which was successfully recycled four times (Figure 14). The observed little decrease of activity in the fourth run is probably ascribed to the aggregation of RhNPs as shown by TEM image taken after recycling experiments. It is due to the deactivation effect of the hydrolysis product metaborate 6-8 that accumulates during the hydrolysis and inhibits the catalytically active Rh surface atoms, and to the diluted reactant in water. The general principle of transition-metal-GO nanocatalysts is extended to the synthesis of AuNPs/GO, PdNPs/GO, CuNPs/GO, and CuPd NPs/GO at 45℃ under identical conditions. In the case of AuNPs/GO, reduction of Au 3+ by GO (Au 3+ /Au 0 = 1.5 V v.s SHE) results in the high efficient AuNPs/GO nanocatalyst with AuNPs of 3.3 nm , as exemplified by the 0.05 mol% AuNPs/GO nanocatalyst catalyzed 4-NP reduction in water without induction time and remarkable efficiency (k app = 3.7×10 -3 s -1 , Figure 13). was then added under Ar, and water was then added in order to obtain a given volume of aqueous solution (2 mL). The mixture was allowed to stir for 24 h at room temperature. After the reaction, 3 mL water was added and the aqueous phase was extracted three times with 5 mL Et 2 O. The organic phase was dried over Na 2 SO 4 , and the solvent was removed in vacuo. In parallel, the reaction was checked using TLC with petroleum ether as the eluent and 1 H NMR spectroscopy. Purification by flash chromatography was conducted with silica gel as the stationary phase and petroleum ether as the mobile phase.

Synergistic CuPd NPs/GO nanocatalyst is an excellent catalyst for Sonogashira coupling in water at rt, i.e. under environmentally-friendly conditions, showing remarkably quantitative conversion with 93% isolated yield in this Sonogashira coupling reaction (Scheme 3 and Figure 15). This work shows a promising way to the rational design of efficient nanocatalysts for a large variety of chemical reactions. Thus in this study, we presented that a simple redox reaction between various transition metal cations and GO has been shown here to lead to the synthesis of ultrafine, surface-clean metal NPs on GO with good monodispersity. The appropriate choice of temperature during the synthesis improved the reduction efficiency and enhanced the interaction between the RhNPs and GO. Consequently, the nanocatalysts showed exceptional efficiency in the 4-NP reduction, hydrolysis of AB to produce H 2 , Sonogashira coupling at room temperature, "click" reaction and hydrolysis of AB for hydrogen production with low amounts of catalytic metals. The principles and catalytic method presented herein could be extended to other transition-metal nanocatalysts and should contribute to the rational design of efficient nanocatalysts for a large variety of chemical reactions.

Introduction

Metal organic frameworks (MOFs) are emerging and outstanding porous nanomaterials, that advantageous compare with other conventional inorganic supports. [1] Catalytically active transition-metal nanoparticles (MNPs) are confined in and stabilized by MOFs within their frameworks to control the nucleation and growth of nanoparticles, which prevents the aggregation of MNPs and prolongs their stabilities. [2] Moreover, the high specific MOF surface areas and tunable pore sizes ensure the good dispersion of MNPs. This allows exposing active sites and facilitate the accessibility of substrates to the active NPs surface by reducing diffusion resistance. On the other hand, the direct use of nanoconfinement effect by MOFs provides a facile method to prepare ligand-free and ultrafine NPs/MOFs nanocatalysts, which is significant but also crucial for the design of highly efficient heterogeneous catalysts.

This chapter highlights the synthesis, characterization and catalytic function of the highly dispersed ligand-free biometal NPs /zeolitic imidazolate framework (ZIF-8;

[Zn(MeIM) 2 ] n ) nanocatalysts, especially with effort to further improve the catalytic activity of nanocatalyts by understandings the mechanistic aspects of the hydrolysis reaction. We show the high efficiency of highly dispersed ligand-free Ni NPs/ZIF-8 nanocatalyst inspired from the mechanistic studies in the hydrolysis of AB in water.

We also discover the ion effect in this reaction allowing a remarkable improvement of the catalytic performance and controlled release of hydrogen.

Introduction

Catalytic hydrogen generation from hydrogen storage materials is considered as a convenient, inexpensive, and effective approach to address the energy and environmental concern. 1-4 Among various chemical hydrogen storage materials, ammonia-borane (AB) has a high hydrogen content (19.6 wt%), high stability in the solid state and solution under ambient conditions, nontoxicity, and high solubility.

Therefore it is considered as one of the most leading contender in promising chemical hydrogen-storage materials for various applications. 5-15 Until now, effective catalysts for hydrolysis of AB are typically based on expensive and rare noble metal nanocatalysts (e.g., Rh, Pt, Ru). Considerable efforts have been devoted to the design of high-performance noble metal-free nanocatalysts, 16-25 On the other hand, the hydrolysis of AB under mild conditions by cheap and earth-abundant experimentally examined, however. In order to address these challenging issues, we

Result and discussion

Synthesis and characterizations of the nanocatalysts:

The ZIF-8 nanoparticles 52 are first rapidly synthesized in water using a modified method (SI). 53 showing the thermal and chemical stabilities of ZIF-8 NPs. 52,53 The nanocatalysts BMNPs/ZIF-8 are prepared using the deposition-precipitation (DP) This comparison demonstrates the best activity of NiNPs/ZIF-8 in terms of turn over 147 frequency (TOF) among the four nanocatalysts BMNPs/ZIF-8 (Table 1 and Figure S11). Therefore the catalytic system NiNPs/ZIF-8 was chosen for further studies.

Figure S12 shows the logarithmic plot of the hydrogen generation rate vs. S14 and calculation). This value also is lower than those found for several known noble metal-based nanocatalysts (Table S1).

Although the catalytic rates in the hydrolysis of AB catalyzed by NiNPs/ZIF-8 is independent of the AB concentration, the KIE 57-59 was further investigated in order to shed light on the RDS of hydrolysis of AB catalyzed by NiNPs/ZIF-8. Indeed in this reaction the KIE value should tell if N-H or B-H or both bonds are broken during the RDS. 16,60-63 The hydrolysis of the deuterated products of AB (for their synthesis, see S.I.) in the presence of NiNPs/ZIF-8 shows slower reaction rates (Figure S17). might be in the RDS. This would be similar to the metal-catalyzed borohydride hydrolysis, in which half of the hydrogen comes from water. 64 Previously, it has been suggested that the water activation by means of oxidative addition of a O-H bond on noble metal NP surfaces easily occurs, forming adsorbed -OH and -H species. For instance Pt NPs have been known as the redox catalyst for water photo-splitting. 65,66 That Ni is the best metal found here for the hydrolysis reaction among those four first-row late transition metals is in accord with oxidative addition of water as the RDS, because Ni(0) is known by far the best first-row metal catalyst of reactions involving oxidative addition. 67 In addition the involvement of water activation in the RDS may be partially explained by the higher O-H bond energy (~493 kJ mol -1 ) 68 than that of B-N and B-H bond (~117 and ~430 kJ mol -1 , respectively). 69 Thus it is mostly likely that the water molecule is activated by an indirect O-H bond cleavage to form -H and -OH species promoted by AB in the presence of the nanocatalyst NiNPs/ZIF-8. Since the NH 3 group does not participate in the hydrolysis, the B-N bond dissociates in AB, followed by H 2 release (Figure 2). In parallel the hydrolysis reaction was also conducted under identical conditions, except that NaOH was replaced by HCl (0.3 M solution for the final concentration), and it was surprisingly found that there was no hydrogen release. Thus in the present study, the contribution from OH -predominated. The influence of OH -and H + disclosed here is different from the very recent work involving AB hydrolysis by single Rh atoms/VO 2 nanorods, which showed positive correlation between the H + concentration and the reaction rate. 71 Density functional theory (DFT) calculations on the interaction of H and OH with (111) metal Ni surface suggested that H forms an essentially covalent bond with the metal, whereas OH forms a largely ionic bond. 72 The weaker covalent interaction and a stronger Pauli repulsion of the OH with the metal d electrons result in the preference of binding molecular hydroxyl to Ni surface rather than H. 73,74 Moreover, Ni is more oxophilic than Pt, so that it can better promote surface OH adsorption than Pt. 75 Therefore the overall reaction activity is significantly improved.

The reason for the switch off of hydrogen generation possibly comes from two aspects. One of them is the negative effect of H + on the self-ionization of water that suppresses the OH -formation and occupation of OH -absorption sites on the NiNP surface. The other one is the ion effect, because Cl -ligands are known to limit the catalytic activity of NPs by strongly bonding to NPs surface, which inhibits access to the surface active sites. We thus first conducted the initial reaction by adding NaCl solution (0.3 M), and found that the H 2 generation rate was slower than that without NaCl solution. H 2 was released smoothly, however, with a TOF of 16.67 mol H2 •mol cat -1 • min -1 (Figure S25). This result suggests the possible ion effect in the reaction. water activation in the RDS of hydrolysis. Thus the negative synergistic effects switched off the hydrogen release. Therefore here we establish for the first time that the anion effect tuned hydrolysis of AB catalyzed by the nanocatalyst NiNPs/ZIF-8 in water, allowing the hydrogen generation to reversibly turn "off" and "on". This property is of great practical importance for on-board hydrogen applications under ambient conditions (vide infra).

The "on-off" control of hydrogen generation is achieved by addition of an equimolar amount of aqueous solution of HCl and NaOH to the reaction media (Figure 3). This material is available free of charge via the Internet at http://pubs.acs.org. We compared their efficiencies in the hydrolysis of AB reaction, showing the best efficiency of NiNPs/ZIF-8 nanocatalyst in term of turnover frequency in this reaction (Figure 5). Therefore the catalytic system NiNPs/ZIF-8 was chosen for further studies. Figure 6a shows the logarithmic plot of the hydrogen generation rate vs. concentration of NiNPs/ZIF-8; the slope is 0.98, indicating that the hydrolysis of AB catalyzed by NiNPs/ZIF-8 is first-order with respect to the catalyst concentration. On the other hand hydrolysis of AB catalyzed by NiNPs/ZIF-8 is zero-order with respect to the AB concentration, as a nearly horizontal line (slope of 0.086) is observed (Figure 6b).

This implies that under the present reaction conditions, AB is easily activated, and thus the possibility of the activation of AB in the rate-determining step (RDS) is ruled out. This also is in accordance with the KIE results. The activation energy (E a ) of AB hydrolysis, determined by measuring the time dependence of H 2 generation at various temperatures, is approximately 42.7 kJ/mol (Figure 7c). strongly bonding to NPs surface, which inhibits access to the surface active sites. By detailed studies, we then firstly disclosed that the "on-off" control of hydrogen generation by addition of an equimolar amount of aqueous solution of HCl and NaOH to the reaction media, which is of great practical importance for on-board hydrogen applications under ambient conditions (Figure 9). Thus, the principles and results here may not only provide insights into the rational design of high efficient non-noble metal based nanocatalysts, but also demonstrate a promising step towards the application of chemical hydrogen storage materials in a fuel-cell-based hydrogen economy.

early transition metal-basec molecular catalysts, although the binding is considerably stronger in the latter case. Both noble metals and biometals using either exergonic or endergonic redox reactions between GO and the transition metal salts have been used

is our general approch. Extension of the scope of the field by exploring novel and efficient transition metal-based nanocatalysts for more and general chemical reactions is also required.

For instance the exploration of new multifunctional nanocatalysts including the design of new bi-and trimetallic nanocomposites, core-shell nanocatalysts is necessary for organic synthesis under harsh conditions. Moreover, considerable efforts should also be devoted to the design of highly efficient earth-abundant transition metal nanocatalysts (Fe, Co, Ni and Cu) for various modern chemical reactions under ambient, green conditions. Furthermore, the activity, selectivity, and recyclability, instability of these nanocatalysts and the leaching of NPs are problems that need be critically addressed. Optimistically one may anticipate that with the increasing attentions paid to the subject, the challenges and problems will be overcome in due course.

Nanomatériaux à base d'éléments de transition tardifs en catalyse

Résumé:

Les nanosciences et nanotechnologies impliquent de travailler avec des matériaux de taille nanométrique avec l'exploration, la caractérisation et l'application de nanomatériaux structurés. Ce domaine a connu beaucoup de succès et est devenu un champ de recherches émergent dans lequel des études significatives ont révolutionné les familles des systèmes nanométriques. 1 Les promesses et possibilités de travaux sont très vastes. Par exemple, les nano machines transformeront la médecine pour la recherche contre le cancer ou pour la délivrance ciblée de médicaments. 2 Les nanomatériaux ont suscité un grand intérêt pour leurs applications en optique, électronique et mécanique et, parmi ces applications, la nano catalyse se trouve en bonne place. En effet, les nano catalyseurs 3 offrent des débouchés dans les domaines des synthèses de médicaments, des conversions d'énergie, de la décontamination pour l'environnement et de la chimie verte pour la production en chimie fine.

Les catalyseurs homogènes sont solubilisés dans les milieux réactionnels et bénéficient d'une grande efficacité, sont très sélectifs et connaissent des utilisations industrielles, mais ils souffrent du manque de leur récupération et de leur réutilisation, ainsi que de leur stabilité thermique très limitée. 4 Par opposition, les catalyseurs hétérogènes bénéficient de leur facilité de récupération à partir des milieux réactionnels et de la possibilité de leur utilisation à haute température. En revanche, ils souffrent de problèmes de sélectivité et de la difficulté des explorations mécanistiques. D'autre part, la catalyse verte qui fait partie intégrante des grands principes de la chimie verte constitue un objectif privilégié des processus chimiques actuels.

Les éléments de cette catalyse verte comprennent idéalement des coût de préparation peu élevés, des activités élevées, de bonnes sélectivités, de hautes sélectivités, des stabilités importantes, un recouvrement efficace et une bonne recyclabilité. Les catalyseurs verts devraient efficacement catalyser les réactions dans des solvants "verts" (par exemple sans solvant, dans l'eau ou dans l'éthanol). Finalement la définition et les applications des catalyseurs verts ne sont pas seulement une tâche de grande importance économique et environnementale pour la science de la catalyse, mais elle doit également se préoccuper de la contamination par les métaux dans les produits de réaction.

La nano catalyse se définit comme la catalyse utilisant les nanoparticules (NP) métalliques. 3 Les nanoparticules actives catalytiquement ont des tailles comprises entre de l'ordre du Sur la base de ce ligand, en bénéficiant en particulier de l'effet chélatant, l'amphiphilie du ligand tris-trz-PEG contenant un tripode tris-triazole accroît la densité électronique sur le centre métallique. La chaine PEG permet, à l'aide de CuNPs, la catalyse homogène des réactions "click" dans l'eau et contribue à procurer au ligand sa nature amphiphile (Figure 4).

Ce catalyseur montre une grande activité pour la réaction "click" dans l'eau à température ambiante avec une charge en catalyseur de seulement quelques ppm pour la synthèse de produits d'intérêt médicinal, catalytique, de ciblage et de marquage. Cette étude contribue à la de catalyseur PEG-tris-trz-Cu I bénéficie de l'effet chélate, de l'amphiphilie du ligand et de la chaîne PEG facilitant les réactions dans l'eau. Cette étude contribue à la synthèse plus efficace de produits "clickés" qui sont utiles en synthèse organique ainsi que dans différents domaines utilisant le Cu(I) ainsi que pour une application industrielle limitant fortement les quantités de Cu introduites.

Le troisième chapitre traite de la préparation de nanoparticules bimétalliques ultrafines Rh-Ag mono dispersées qui sont uniformément supportées sur des nano-feuillets d'oxyde de graphène réduit (RhAg/rGO, Figure 5). Les nanoparticules Rh-Ag font intervenir une synergie électronique entre les deux métaux sur l'oxyde de graphène réduit qui améliore

Transition Metal Nanomaterials in Catalysis

Abstract: Transition metal nanocatalysis is a promising area, where increased efficiency, greenness and reusability are actively sought. In this spirit, the thesis has been devoted to the synthesis, characterization and catalytic applications of new transition metal nanomaterials. Amphiphilic ligand stabilized transition metal nanoparticles catalysts have provided excellent catalytic performances in terms of activity, stability and recyclability in the 4-nitrophenol reduction, Suzuki-Miyaura coupling, transfer hydrogenation and alkyne-azide cycloaddition reactions with low amounts of metal loadings. Moreover, an efficient amphiphilic "click" Cu I catalyst was also designed for part-per-million levels of alkyne-azide cycloaddition reaction in water.

The design, synthesis and catalytic application of heterogeneous nanocatalysts based on graphene and metal organic framework supports have also been carried out, and their excellent catalytic properties in 4-nitrophenol reduction, Sonogashira coupling, alkyne-azide cycloaddition and hydrolysis of ammonia-borane for hydrogen generation in water under ambient conditions have been disclosed.

Keywords:

Transition metal, nanomaterials, catalysis, amphiphilic ligand, support, green chemistry, graphene, MOF

  in a review paper written in collaboration between our group and Prof. Jean-Yves Saillard from the University of Rennes on copper-catalyzed azide-alkyne cycloaddition reactions (CuAAC) and other metal-catalyzed azide-alkyne cycloaddition reactions (MAAC). It contains over 200 references disclosing the recent developments in the mechanistic aspects and recent trends of the MAAC reactions based on various metals (Cu, Ru, Ag, Au, Ir, Ni, Zn, Ln). The MAAC reactions are of considerable use in synthesis with applications in materials science and biomedicine, although CuAAC reactions remain by far the most prominent example of MAAC reactions and "click" chemistry. Various mechanisms based on theoretical calculations, characterizations of intermediates and optimization of reaction parameters have been proposed for different MAAC reactions. The theoretical calculations and experimental progress are intimately connected in order to improve the reaction efficiency, simplify procedures and apply them to industry in particular by decreasing catalytic amounts. Thus we reviewed the mechanistic advances and recent trends of this MAAC "click chemistry". These multiple new advances should inspire theoretical chemists to rationalize mechanisms of new routes.

Fig. 1 .

 1 Fig. 1. The CuAAC mechanisms (Sharpless-type catalysis) proposed by Fokin and coworkers from their DFT calculations. Top: proposed mononuclear mechanism. Bottom: proposed dinuclear mechanism.

Fig. 2 .

 2 Fig. 2. Fokin's proposed mechanism for the CuAAC reaction with two copper centers. Reproduced with permission from Ref. [38]. Copyright 2013, American Association for the Advancement of Science.

Fig. 4 .

 4 Fig. 4. Nolan's proposed multiple mechanistic pathways for the [3 + 2] cycloaddition of azides to alkynes.

Fig. 5 .

 5 Fig. 5. Photoinduced CuAAC click reaction pathways. Reprinted with permission from Ref. [69a]. Copyright 2013, Wiley-VCH.

Fig. 6 .

 6 Fig. 6. Reaction mechanism proposed for the CuNPs-catalysed 1,3-dipolar cycloaddition of terminal alkynes and azides. Reproduced with permission from Ref. [80]. Copyright 2010, WILEY-VCH.

Fig. 7 .Fig. 8 .

 78 Fig. 7. Activation of the precatalyst and catalytic mechanism of the RuAAC of phenylacetylene with benzylazide. Numbers colored in blue and in red are computed relative free energies of intermediate and transition states, respectively (in kcal/mol).Reproduced with permission from Ref.[88]. Copyright 2012, American Chemical Society.

  14-electron catalyst I, forming the ligated silver(I) acetylide II, the electrophilicity of which is modulated by the hemilabile amide substituent. The nucleophilic reaction of the azides on II gives the species IIIA. The hemilabile ligand in IIIA intervenes by amide complexation generating a coordinatively saturated species that transfers the charge via the filled d orbitals to the * orbitals of the acetylide resulting in cyclization. The reaction occurs via the intermediate metallacycle (IIIB). Then the nitrogen atom migrates to carbon transporting two electrons to form the triazole IV, forming 3 by protonation, and the active catalyst I is regenerated.

Fig. 10 .

 10 Fig. 10. Proposed mechanism of the RuAAC catalysis by ruthenium azido complexes. Reprinted with permission from Ref. [91]. Copyright 2014, Elsevier B.V.

Fig. 11 .

 11 Fig. 11. Proposed catalytic cycle for the homogeneous Ag(I)-catalyzed AAC reaction. Reproduced with permission from Ref. [93]. Copyright 2012, WILEY-VCH.

Fig. 12 .

 12 Fig. 12. One-pot AAC reaction catalyzed by Ag/GO. Reproduced with permission from Ref. [95]. Copyright 2014, Royal Society of Chemistry.

Fig. 13 .

 13 Fig. 13. (a) On Cu(111) surface catalyzed AAC. (b) Proposed on-surface AAC reaction of N-(4-azidophenyl)-4-ethynylbenzamide (AEB) and possible regioisomeric dimers 2 and 3.

Fig. 14 .

 14 Fig. 14. (a) Titania-supported gold nanosphere-catalyzed 1,2,3-triazole synthesis. (b) Plausible mechanism for the formation of triazole.Reproduced with permission from Ref.[102]. Copyright 2013, American Chemical Society.

Fig. 15 .

 15 Fig. 15. Synthesis of 1,4,5-trisubstituted triazoles catalyzed by a dimeric iridium complex.

Fig. 16 . 20 Fig. 17

 162017 Fig.16. The different IrAAC mechanisms proposed in the case of the addition of thioalkynes and bromoalkynes to azides in the presence of the [Ir(cod)X]2 (X = Cl or OMe) dimer.Reproduced with permission from Ref.[105]. Copyright 2014, American Chemical Society.

  Fig. 17.(a) Combinatorial cycloaddition of two aryl propargyl ethers to benzyl and n-hexyl azides catalyzed by Raney Ni, and (b) Proposed mechanism for the NiAAC. Reproduced with permission from Ref. [106]. Copyright 2014, Royal Society of Chemistry.

  Fig. 17.(a) Combinatorial cycloaddition of two aryl propargyl ethers to benzyl and n-hexyl azides catalyzed by Raney Ni, and (b) Proposed mechanism for the NiAAC. Reproduced with permission from Ref. [106]. Copyright 2014, Royal Society of Chemistry.

Fig. 18 .

 18 Fig. 18. Zn/C-catalyzed AAC reactions. Reproduced with permission from Ref. [108]. Copyright 2010, WILEY-VCH.

Fig. 19 .

 19 Fig. 19. Proposed mechanism explaining the reactivity in the system mediated by ZnEt2. Reproduced with permission from Ref. [109a]. Copyright 2013, American Chemical Society.

Fig. 20 .

 20 Fig. 20. (a) [Ln{N(SiMe3)2}3]-catalyzed cycloaddition of terminal alkynes with azides (Ln = Sm, Nd, Y, Gd). (b) Reaction pathway for [Ln{N(SiMe3)2}3]-catalyzed cycloaddition between terminal alkynes and azides. Reproduced with permission from Ref. [110]. Copyright 2013, Royal Society of Chemistry.

Fig. 22 .

 22 Fig. 22. NHC or phosphine-containing copper(I) complexes for the synthesis of 5iodo-1,2,3-triazoles. Reproduced with permission from Ref. [112a]. Copyright 2014 American Chemical Society.

Fig. 23 .

 23 Fig. 23. (a) Copper(I)-triazolylidene complexes. (b) aNHC coordinated copper(I) chloro complex.

Fig. 24 .

 24 Fig. 24. Chit-CuSO4 catalyzed dipolar cycloaddition of benzyl azide and phenyl acetylene (Chit = chitosan). Reproduced with permission from Ref. [132]. Copyright 2013, Royal Society of Chemistry.

Fig. 25 .

 25 Fig. 25. Synthesis of the Cu@PyIm-SBA-15 catalyst. Reproduced with permission from Ref. [134a]. Copyright 2014, Elsevier B.V.

14 C .

 14. Wang et al. / Coordination Chemistry Reviews 316 (2016) 1-20

Fig. 26 .

 26 Fig. 26. (a) Structure of Cu(II)-TD@nSiO2, (b) Cu(II)-TD@nSiO2-catalyzed three-component synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl/benzyl halides. Reproduced with permission from Ref. [136]. Copyright 2014, American Chemical Society.

Fig. 27 .

 27 Fig. 27. AAC reactions catalyzed by Cu2O-NP and CuSO4/NaAsc. Reproduced with permission from Ref. [142]. Copyright 2013, Elsevier B.V.

Fig. 28 .

 28 Fig. 28. Schematic illustration of the bulk CuAAC reaction of PIB-azide and PIBalkyne with TRGO/Cu(I) at 20 • C via melt rheology. Reprinted with permission from Ref. [145a]. Copyright 2014, Royal Society of Chemistry.

Fig. 29 .

 29 Fig. 29. CuNPs or their clusters catalyzed solvent-free AAC reaction. Reproduced with permission from Ref. [151]. Copyright 2012, Elsevier B.V.

Fig. 30 .

 30 Fig. 30. Multicomponent synthesis of 1,2,3-triazoles from various azide precursors catalyzed by CuNPs/C in water.

16 C . 20 Fig. 31 .

 16.2031 Fig. 31. Tris(aryltriazolyl)methanol ligands. Reproduced with permission from Ref. [166c]. Copyright 2009, American Chemical Society.

Fig. 32 .

 32 Fig. 32. MNPs-CuBr catalyzed one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles in water under microwave irradiation conditions.Reprinted with permission from Ref.[172]. Copyright 2013, Royal Society of Chemistry.

Fig. 33 .

 33 Fig. 33. (a) Magnetically recyclable Cp*(PPh3)2Ru/SiO2/␥-Fe2O3 catalyst. (b) Catalytic performance of magnetic catalyst in cycloaddition of phenylacetylene and benzyl azides. Reproduced with permission from Ref. [184]. Copyright 2013, Royal Society of Chemistry.

Fig. 34 .

 34 Fig. 34. Sequential one-pot RuAAC reaction under microwave heating. Reproduced with permission from Ref. [187]. Copyright 2011, American Chemical Society.

  proposed a ligand design by conceptualizing the efficient amphiphilic dendrimers with tris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand. The tris-trz-PEG ligand stabilized various ultrafine transition metals NPs, showing high efficiencies in the 4-nitrophenol reduction, click reaction, Suzuki-Miyaura reaction and transfer hydrogenation reaction with only part per million metal loading in water under ambient conditions. In the second part we compare the stabilization of AuNPs by mono-, bis-, and tris-trz and their influence of the trz denticity on the 4-NP reduction by NaBH 4 in water also including comparison with current polyethylene glycol 2000 (PEG) and polyvinylpyrrolidone (PVP) AuNP stabilizers. We show the benefit of utilizing tris-trz-PEG amphiphilic ligand for efficient and ultrafine transition metals NPs stabilization.

German

  Edition:D OI:10.1002/ange.201511305 Nanocatalysts International Edition:D OI:10.1002/anie.201511305

[

  *] C. Wang, Dr.R .C iganda, Dr.J .Ruiz, Prof. D. Astruc ISM, UMR CNRS No 5255, Univ.Bordeaux 33405 Talence Cedex (France) E-mail:d.astruc@ism.u-bordeaux1.fr Dr.R .Ciganda Facultad de Quimica de San Sebastian Universidadd el Pais Vasco Apdo. 1072, 20080 San Sebastian (Spain) Dr.L .Salmon Laboratoire de Chimie de Coordination, UPR CNRS No 8241 31077 Toulouse Cedex (France) Dr.D .Gregurec, Dr.J.Irigoyen, Dr.S.Moya CIC biomaGUNE, Unidad Biosuperficies Paseo Miramon No 182, Edif "C" 20009 Donostia-SanS ebastian (Spain) Supportinginformation and ORCID(s)f rom the author(s) for this article are available on the WWW under http://dx.doi.org/10.1002/anie.201511305.

Figure 1 .

 1 Figure 1. a) Synthesis of the amphiphilic ligand 2.b)Synthesis of the TMNP-2.

Figure 2 .

 2 Figure 2. Characterization of TMNP-2.a)X-ray photoelectron spectroscopy (XPS) of Au 4f.T ypical TEM images of the as-synthesized: b) AuNPs, c) PdNPs, d) AgNPs, and e) PtNPs. Foradditionalc haracterization of TMNP-2,s ee the SupportingInformation,S ection 3.

[ a ]

 a Amount of TMNP-2 used in the catalyzed 4-NP reduction.NaBH 4 is in excess. [b] Core size (TEM) of the TMNP-2.[c] Induction time. [d] Rate constant.[ e] Surface-independent rate constant.

Figure 3 .

 3 Figure 3. a) X-ray photoelectron spectroscopy of Cu 2p. b) Cu LMM Auger spectra.

Figure 1 .

 1 Figure 1. Ligands used in this study for AuNP stabilization.

  It was finally of interest to investigate the AuNP formation in the presence of the ligand 5 under various conditions in order to compare various key points concerning efficient nanogold catalysts preparations. Although both Au III and Au I compounds are well-known, AuNP precursors for AuNP syntheses are almost exclusively based on Au III derivatives (e.g., HAuCl 4 • 3H 2 O or AuCl 3 ), while less efforts have been paid to the use of Au I compounds as precursors.

Figure 2 .

 2 Figure 2. TEM images of various AuNP-L samples. (a) AuNP-1; (b) AuNP-2; (c) AuNP-3; (d) AuNP-4; (e) AuNP-5; (f) AuNP-6. Scale bar: 100 nm. For other TEM images and size distributions see the Supporting Information.

Table 1 . 4 -( 1 ×ad

 141 NP Reduction to 4-AP by NaBH 4 Catalyzed by Various AuNP-L (20 °C) a AuNP-L SPB (nm) size (nm) c induction time (s) K app d 10 -3 s -1 ) Conditions: 4-NP (1 equiv), NaBH 4 (81 equiv), and AuNP-L catalysts (0.2 mol %). b Data are shown using 3 trz per AuNP; data in brackets are using 1 trz per AuNP. c Core size (TEM) of AuNP-L. Rate constant.

  Scheme 1

■

  ASSOCIATED CONTENT Design and Applications of an Efficient Amphiphilic "Click" Cu I Catalyst in Water Changlong Wang, † Dong Wang, † Shilin Yu, † Thomas Cornilleau, † Jaime Ruiz, † Lionel Salmon, ‡ and Didier Astruc* , † † ISM, UMR CNRS No. 5255, Univ. Bordeaux, 33405 Talence, France ‡ Laboratoire de Chimie de Coordination, UPR CNRS No. 8241, 31077 Toulouse, France * S Supporting Information

  KEYWORDS: "click" reaction, CuAAC, tris-trz-PEG, Cu I , parts per million, catalyst, triazole

Figure 1 .

 1 Figure 1. Synthetic process for the PEG-tris-trz-Cu I catalyst monitored by UV-vis spectroscopy.

Figure 2 . 56 ■

 256 Figure 2. Comparison studies among Cu I , PEG-Cu I , PEG-monotrz-Cu I , and PEG-tris-trz-Cu I catalysts in the CuAAC reaction between benzyl azide and phenylacetylene.

Financial 1 H) . Scheme 1 .

 1.1 Scheme 1. Synthesis of tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol.

  Figure 1. 1 H NMR (CDCl 3 , 300 MHz) spectrum of tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol, 1.

Figure 2 . 3 Scheme 2 .

 232 Figure 2. Synthesis of the new amphiphilic ligand 2(n = 40-44).

Figure 4 .

 4 Figure 4. 1 H NMR (CDCl 3 , 300 MHz) spectrum of biphenyl, δ ppm : 7.37-7.43 (m, 2H),

Figure 5 . 1 H

 51 Figure 5. 1 H NMR spectrum (300 MHz, CDCl 3 ) of aniline. δ ppm : 3.69 (s, 2H),

Figure 6 . 1 H

 61 Figure 6. 1 H NMR spectrum of 1-benzyl-4-phenyl-1H-[1,2,3]triazole.

Figure 7 .

 7 Figure 7. The summary of the working principles of tristrz-PEG ligand in both

Figure 8 .

 8 Figure 8. Ligands used for AuNP stabilization. 1 1.2.3, triazole; 2 bis-triazole; 3 PEG

Scheme 6 .

 6 Scheme 6. Synthesis of 1,3-di(1H-1,2,3-triazol-1-yl)propane, 2.

Figure 9

 9 Figure 9. 1 H NMR (CDCl 3 , 300 MHz) spectrum of 1,3-di(1H-1,2,3-triazol-1-yl)propane, 2. (δ ppm =7.68 (2H), 7.63 (2H), (δ ppm =4.73, J=6.3 Hz, 2H), (δ ppm =2.53 J=6.3 Hz, 2H).

Figure 10 .

 10 Figure 10. UV-vis. absorption spectrum of the AuNP-5-THT (left); Consumption

  I catalyst was designed by addition of CuSO 4 •5H 2 O under nitrogen to an aqueous solution containing the amphiphilic tris-trz-PEG ligand, then in situ reduction of the pre-catalyst PEG-tris-trz-Cu 2+ to the PEG-tris-trz-Cu I catalyst by dropwise addition of NaAsc (Figure 11).

Figure 11 .

 11 Figure 11. Synthesis of the PEG-tris-trz-Cu I "click" catalyst.

Figure 12 .

 12 Figure 12. Substrate scope of CuAAC reactions between various azides and alkynes

Figure 8 .

 8 Figure 8. Application of the PEG-tris-trz-Cu I catalyst to the synthesis of functional

Introduction

  Noble bimetallic nanoparticles (NBNPs) have received considerable interest owing to their composition-dependent optical, electronic and catalytic properties and have been successfully applied to the homogeneous and heterogeneous catalysis of various organic and inorganic reactions[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The facile blending of two metals or the incorporation of two metals often enhances the catalytic activity and Address correspondence to E-mail: d.astruc@ism.u-bordeaux.fr DOI 10.1007/s10853-017-1158-7

1

 1 Scheme 1 Synthesis of the RhAg/rGO catalysts.

Figure 1

 1 Figure 1 Typical TEM images of a GO and b RhAg 0.5 /rGO; c and d are STEM dark-field image and HRTEM images of the RhAg 0.5 / rGO catalyst at different magnification.

Figure 2

 2 Figure 2 XPS spectra of a Ag 3d, and b Rh 3d over RhAg 0.5 /rGO catalyst.

Figure 3 a

 3 Figure 3 a Reusability of the RhAg 0.5 /rGO catalyst for the 4-NP reduction by NaBH 4 . b Plot of -ln(C t /C 0 ) versus time for the reduction of 4-NP by NaBH 4 in the presence of 0.05 and 0.01% RhAg 0.5 /rGO catalysts.

Fig. 2

 2 Fig. 2 Consumption rate of 4-NP: Àln(C t /C 0 ) vs. time.

Figure 1 .

 1 Figure 1. (a) STEM image and (b) HRTEM of the RhNPs/GO-45℃ nanocatalyst. XPS spectra of C1s on (c) GO and (d) RhNPs/GO-45℃ nanocatalyst.

  Figure 1a shows the STEM image of RhNP/GO from the synthesis at 45℃. It is striking that the 1.8±0.3 nm RhNPs are fairly monodisperse on the GO surfaces. A high-resolution TEM (HRTEM) image (Figure 1b) of the RhNPs shows that the interplanar spacing of the particle lattice is 0.23 nm, corresponding to the (111) lattice spacing of face centered cubic Rh. X-ray photoelectron spectroscopy (XPS) was further recorded to investigate the surface nature of the RhNPs and GO. Comparison of the binding energy (B.E.) between the C1s spectra of GO and RhNP/GO clearly shows that after the reaction the peaks associated with the C-C bonds (B.E. = 284.6 eV) become predominant (Figure 1c), whereas the additional peak of C-O (B.E. = 286.6 eV) decreases during Rh 3+ reduction (Figure1d).[5a] The reducing nature of GO is due to the oxygenated functional groups attached to the hexagonal basal plane, further suggesting that these oxygenated functional groups (e.g. -OH, -COOH, epoxy) on the GO nanosheets play an important role of nanoparticles stabilizing ligands with the lone pairs of the oxygen atoms in the formation of RhNPs.[9] The B. E. values at 307.6 and 312.8 eV are assigned to Rh 3d5/2 and Rh 3d3/2 of Rh(0) respectively,[10] indicating the presence of metallic Rh (FigureS10). A ca.1 eV red shift of XPS peak of these very small RhNPs is observed and compared to bulk Rh, which is typical for very small metal NPs on a variety of support materials and is generally attributed to the reduced core-hole screening in metal clusters.[5b] Such a sizedependent alteration of electronic structures[5b] is seemingly concomitant with the enhanced catalytic properties (vide infra).

Figure 2 .

 2 Figure 2. Proposed mechanism for the hydrolysis of AB by catalyzed by RhNP/GO-45℃.

Figure 1 .

 1 Figure 1. Synthesis of the RhAg/rGO catalysts.

Figure 2 .

 2 Figure 2. (a) UV-vis. spectra of the 4-NP reduction by NaBH 4 catalyzed by RhAg 0.5 /rGO (top); (b) consumption rate of 4-NP: -ln(C t /C 0 ) vs. reaction time .

Figure 4 .

 4 Figure 4. (a) UV-vis. spectra of the 4-NP reduction by NaBH 4 catalyzed by 0.05 mol%

Figure 5 .

 5 Figure 5. Synthesis of the catalyst α-Fe 2 O 3 /graphene oxide, 1.

  4 and 712.3 eV are shown in the Fe 2p spectrum, which correspond to Fe 2p 1/2 and Fe 2p 3/2 core level of the α-Fe 2 O 3 , respectively. Moreover the shakeup satellite peak at about 719.0 eV also suggested the presence of Fe 3+ species (Figure6).

Figure 6 .

 6 Figure 6. XPS of the catalyst 1. C 1s spectrum (a) and Fe2p (b).

Figure 7 .

 7 Figure 7. UV-vis. spectra for the 4-NP reduction by NaBH 4 catalyzed by 1 (left);

  To prove the heterogeneity of the Suzuki-Miyaura reaction by α-Fe 2 O 3 /GO, hot filtration test was conducted. The standard Suzuki-Miyaura reaction between bromobenzene and phenylboronic acid proceeded well in the presence of the catalyst, whereas removal of the catalyst at half way inhibited continuation of the reaction (Figure8). Moreover, no residual Pd was found in the α-Fe 2 O 3 nanocluster/GO catalysts. Catalyst also can be recovered and reused four times without significantly loss of catalytically active NPs and activities.

Figure 8 .

 8 Figure 8. Hot filtration test of the standard Suzuki reaction in the presence of

  45 mg of graphene oxide was dispersed in 100 mL of water to obtain a yellow colored solution with ultrasonic treatment. Then, 6 mL of this GO solution was taken and injected into a Schlenk flask with continuous stirring at the given temperature in an oil bath. The temperature of the GO solution is controlled by an external thermometer.

4 -

 4 nitrophenol reduction by RhNP/GO, AuNP/GO and CuNP/GO, Sonogashira coupling by CuNP/GO, PdNP/GO, and PdCuNP/GO, azide-alkyne 1,3-cycloaddition by CuNP/GO, and hydrolysis of ammonia-borane for hydrogen generation by RhNP/GO catalyst (Figure10).

Figure 10 .

 10 Figure 10. Transition metal NP/GO nanocatalysts in water under ambient conditions

Figure 11 .

 11 Figure 11. Consumption rate of 4-NP in the presence of 1 ppm of the nanocatalyst

Figure 12 .

 12 Figure 12. (a) The plot of hydrogen generation rate vs. the concentration of

Figure 13 .

 13 Figure 13. Proposed mechanism for the hydrolysis of AB by catalyzed by

Figure 14 .

 14 Figure 14. Time plots of the catalytic dehydrogenation of AB by the nanocatalyst

Figure 13 . 4 -

 134 Figure 13. 4-NP reduction catalyzed by 0.05mol% AuNPs/GO nnaocatalyst:

Figure 15 . 1 H

 151 Figure 15. 1 H NMR spectrum of 1-benzyl-4-phenyl-1H-[1,2,3]triazole.

Figure 14 .

 14 Figure 14. X-ray photoelectron spectroscopy of Cu 2p. In sample Cu/GO both species

Figure 15 . 1 H

 151 Figure 15. 1 H NMR spectrum of diphenylacetylene (CDCl 3 400 MHz) δ ppm : 7.34-

  now report the synthesis, characterization and catalytic functions of the BMNPs/zeolitic imidazolate framework (ZIF-8; [Zn(MeIM) 2 ] n ) nanocatalysts, especially with efforts to further improve the catalytic activity by understanding the mechanistic aspects of the hydrolysis reaction. First, the supporting nanomaterial of ZIF-8 is synthesized and characterized. Then we highlight the efficiency of Ni NPs/ZIF-8 nanocatalyst by comparing the catalytic activities of first-row late transition-metals NPs/ZIF-8 catalysts in the hydrolysis of AB in water under mild conditions. Subsequently we scrutinize the catalytic behavior of Ni NPs/ZIF-8 nanocatalysts for the hydrolysis of AB in water, the mechanistic aspects of this reaction using kinetic isotope effects (KIEs), and an anion effect for the control of hydrogen release. The catalytic activity of the nanocatalyst Ni NPs/ZIF-8 surpassed all the non-noble metal NP systems for the hydrolysis of AB.

  Transmissionelectron microscope (TEM) image indicates that the ZIF-8 NPs are nanocrystals with sharp hexagonal facets, and the average size of ZIF-8 NPs is around 75 nm (FigureS1). Powder X-ray diffraction (PXRD) proves the pure phase of ZIF-8 nanomaterial (FigureS2). ZIF-8 NPs show a type I isotherm in the N 2 adsorption measurement. The presence of micropores results in volume increase adsorbed at very low relative pressures, whereas a second uptake at a high relative pressure indicates the existence of textural meso/macroporosity formed by the packing of NPs (FigureS3). The Brunauer-Emmett-Teller (BET) surface area of ZIF-8 NPs is 1663.3 m 2 g -1 . Refluxing the ZIF-8 NPs in either methanol or water during one day does not change the framework structure, as evidenced from the unchanged PXRD patterns (FigureS2),

  method with fast reduction by NaBH 4 , then collected by centrifugation followed by washing and drying in vacuo (Scheme 1 and SI). These nanomaterials are clearly distinguished by their colors (compare the photographs in Figure S4); for instance Ni NPs/ZIF-8 appears grey, whereas Cu NPs/ZIF-8 is completely black. No diffractions are detected for Ni NP species from PXRD patterns after reduction in Ni NPs/ZIF-8 compared to ZIF-8 NPs, which indicates that Ni loadings are too low or Ni NPs are too small.

Figure 1 .

 1 Figure 1. TEM images of NiNPs/ZIF-8: (a) at 500 nm scale. (b) at 20 nm scale. (c)

Figure 2 .

 2 Figure 2. Proposed mechanism for the hydrolysis of AB catalyzed by NiNPs/ZIF-8.

  To confirm this, XPS is re-called to measure the surface binding energy of Ni 2p upon treatment with NaOH. As shown in Figure S23, upon treatment with NaOH, the binding energy at 855.6 eV that associates with Ni(OH) 2 species 76 becomes predominant, verifying the coordination of OH group to the Ni surface. On the other hand, a ca. 0.76 eV Ni 2p binding energy downshift was also observed. Thus upon coordination of OH group to the Ni surface, the OH adsorbates donate electrons to the Ni surface. This results in an increased electron density around the Ni surface, which facilitates the interaction with the reactant, AB. The E a of AB hydrolysis in the presence 0.3 M NaOH was considerably decreased to 28.0 kJ/mol (Figure S24).

Figure 3 .

 3 Figure 3. "On-off" control of H 2 production in the AB hydrolysis in water.

Figure 4 .

 4 Figure 4. Plots of volume of H 2 vs. time for the hydrolysis of AB catalyzed by the 3%

Figure 1 .

 1 Figure 1. PXRD patterns of as-synthesized ZIF-8 NPs and ZIF-8 NPs refluxing in

Figure 2 .

 2 Figure 2. Preparations of the nanocatalyst BMNP/ZIF-8.

Figure 3 .

 3 Figure 3. Size distributions of the NPs after digestion of nanocatalysts with EDTA,

Figure 4 .

 4 Figure 4. Nitrogen adsorption-desorption isotherms of ZIF-8 and BMNPs/ZIF-8

Figure 5 .

 5 Figure 5. Comparison of the Hydrogen evolution from NH 3 BH 3 in H 2 O in water in

Figure 7 .

 7 Figure 7. (a) The plot of hydrogen generation rate versus the concentration of Ni

Figure 9 .

 9 Figure 9. Enhancing the catalytic efficiency of nanocatalyst NiNPs/ZIF-8 in

Figure 10 .

 10 Figure 10. (a) PXRD patterns of as-synthesized NiNPs/ZIF-8 NPs before and after

4

 4 nanomètre (nm) et plusieurs dizaines ou centaines de nanomètres (contenant de quelques dizaines à quelques milliers d'atomes). Elles ont un rapport surface sur volume élevé et un grand pourcentage d'atomes de surface, c'est-à-dire de façon prédominante des atomes de surface sur les coins et les arêtes. Depuis approximativement le début des années 1990, ce domaine de la catalyse a acquis son Independence. Il est habituellement appelé catalyse colloïdale ou catalyse semi-hétérogène car on lui attribuait alors de constituer un pont entre la catalyse homogène et la catalyse hétérogène. De cette façon, la nano catalyse combine les aspects positifs de la catalyse homogène avec une haute activité catalytique et une bonne sélectivité, ainsi que la possibilité d' études mécanistiques permettant des améliorations des catalyseurs de même qu'une bonne recyclabilité. Dans ce contexte, les nanomatériaux à base d'éléments de transition sont d'un intérêt particulier pour l'utilisation de nano catalyseurs. 5,6 Les nanomatériaux hétérogènes à base d'éléments de transition contiennent les entités catalytiquement actives qui conduisent à l'activation des substrats et les réactions catalytiques procèdent sur les surfaces des matériaux supportés conduisant à l'efficacité et à la sélectivité. De façon à obtenir des nanoparticules catalytiquement actives nanométriques, les tailles des nanoparticules doivent être réduites à quelques dizaines à quelques milliers d'atomes. C'est la raison pour laquelle les nanoparticules à base d'éléments de transition tardifs ont la nécessité d'être stabilisés par des dendrimères, polymères, liquides ioniques et supports inorganiques solides tels que la silice, l'alumine, la zircone, le carbone sous ses différentes formes, etc. Dans les faits, les stabilisants jouent un rôle crucial et ont une influence sur les propriétés catalytiques. 7 Par exemple, certains ligands fortement coordonnants (thiolates, phosphines, oxydes de phosphine, etc.) inhibent les sites catalytiquement actifs de la surface du catalyseur, ce qui conduit à des effets catalytiques négatifs se développant sur la surface des nanoparticules. Par conséquent, les ligands "verts" qui impliquent une stabilisation douce dans l'eau et sont facilement déplaçables par les substrats de la surface catalytique en procurant éventuellement un nombre accru de sites catalytiquement actifs sont particulièrement recherchés afin d'améliorer les efficacités catalytiques. Effectivement, la synthèse rationnelle de catalyseurs à base de nanoparticules sans ligands, ultrafines et efficaces constitue actuellement un défi notable.Avant la présente thèse de PhD, notre groupe de recherche a examiné l'efficacité des dendrimères en tant que supports des nanoparticules à base d'éléments de transition tardifs et templates pour des réactions catalytiques homogènes et hétérogènes.8 Nous avons étendu le principe de la catalyse à l'aide de template dendritiques de nanoparticules métalliques à la nano catalyse induite par des ligands, en particulier à des nanomatériaux à base de ligand amphiphile triazole (click) dans le but d'améliorer les efficacités catalytiques. Par conséquent, la présente thèse de PhD implique le design et l'application de nanomatériaux à base d'éléments de transition tardifs en tant que nouveaux nano catalyseurs pour une variété de réactions chimiques avec un objectif de nano-ingénierie de la taille et de l'environnement de façon à améliorer l'activité catalytique, la stabilité des nano catalyseurs, leur recouvrement et à décroître la charge de catalyseur.Dans le premier chapitre, un article de revue écrit en collaboration entre notre groupe et le groupe du Professeur Jean-Yves Saillard de l'Université de Rennes sur les aspects théoriques et les recherches récentes concernant la catalyse de réactions "click", en fait la principale de ces réactions, c'est-à-dire la cycloaddition1-3 de type Huisgen entre un alcyne et un azoture catalysée par le cuivre (en abrégé anglais CuAAC), mais aussi par une variété d'autres éléments de transition et lanthanides (Cu, Ru, Ag, Au, Ir, Ni, Zn, Ln) (en abrégé anglais MAAC), (Figure1).9 Ces réactions MAAC sont parmi les plus utilisées des réactions en chimie "verte", et sont les plus fréquemment utilisées des diverses réactions dites "click". D'abord développées par le groupe de Sharpless et par celui de Meldal en 2002 avec Cu(I) 10 , ces réactions ont ensuite é t é étendues par Fokin à des catalyseurs au Ru(II) en 2005, puis à beaucoup d'autres éléments de transition catalytiques. Des mécanismes variés basés sur des calculs théoriques et des résultats expérimentaux comprenant la caractérisations d'intermédiaires réactionnels et optimisations de paramètres de réactions qui sont intimement connectés ont été proposés pour les diverses réactions MAAC catalysées par ces composés métalliques. Les objectifs sont l'optimisation des conditions réactionnelles et des catalyseurs, la simplification des procédures, leur application dans l'industrie et la diminution des quantités de catalyseurs employées.Depuis 2012, de nouvelles tendances sont apparues souvent représentant à la fois des découvertes incisives pour de nouvelles applications et de nouveaux défis mécanistiques. Ces avancées récentes doivent inspirer les chimistes théoriciens pour rationaliser les mécanismes de nouvelles voies catalytiques.

Figure 1 .

 1 Figure 1. Réactions de cycloaddition 1-3 des alcynes avec les azotures catalysées par des composés des éléments de transition.

Figure 2 . 11 DTableau 1 :a

 2111 Figure 2. a) Synthèse du nouveau ligand amphiphile 2. b) Synthèse des nanoparticules des éléments de transition (en abrégé anglais TMNP-2).

Figure 3 .

 3 Figure 3. Ligands utilisés pour la stabilisation de nanoparticules d'or: 1 1.2.3, triazole; 2 bistriazole; 3 PEG 2000; 4 mono-triazole-PEG; 5 tris-triazole-PEG; 6 PVP (masse moléculaire Mw = 10.000).

1 g - 1 )

 11 l'activité catalytique entre les deux métaux par comparaison avec les deux nanoparticules de chaque métal prises séparément. En faisant varier le rapport Rh/Ag, nous avons pu montrer que la meilleure activité catalytique se trouve au niveau de RhAg 0.5 /rGO pour la réduction du 4-nitrophénol. La réutilisation a également été examinée, et le catalyseur RhAg 0.5 /rGO a pu être réutilisé cinq fois sans perte significative d'activité dans cette réaction. Lors de la cinquième réutilisation, la constante de vitesse pour la réduction du 4-nitrophénol par NaBH 4est encore de k app = 12.1 ×10 -3 s -1 , ce qui suggère que le catalyseur RhAg 0.5 /rGO montre une très bonne possibilité de recyclage pour cette réaction. Cette efficacité catalytique est également supérieure à celle rencontrée pour la plupart des catalyseurs à base de nanoparticules d'éléments de transition du groupe des métaux nobles. La décroissance de la quantité totale de catalyseur de réaction a également été examinée. Avec 0,05 mol% et 0,01 mol% du catalyseur RhAg 0.5 /rGO, la vitesse de réaction est k app = 8.2 ×10 -3 s -1 (k nor = 3140 s -et k app = 5.3 ×10 -3 s -1 (k nor = 10140 s -1 g -1 ), respectivement, démontrant le succès du design du catalyseur RhAg 0.5 /rGO.13

Figure 5 .

 5 Figure 5. Synthèse du catalyseur RhAg/rGO.

Figure 6 .

 6 Figure 6. Nano catalyseurs à base de nanoparticules de métaux de transition supportés sur oxyde de graphène montrant d'excellentes efficacités à température ambiante pour la réduction du 4-nitrophénol par NaBH 4 en 4-aminophénol, l'hydrolyse de l'ammoniac-borane avec génération de H 2 , la réaction de Sonogashira et la réaction "click".

Figure 7 .

 7 Figure 7. Préparation des nano catalyseurs BMNP/ZIF-8.

  . For CuNP-catalyzed AAC, Scaiano et al. successively proved that catalysis occurred at the surface of the CuNPs by standard bench scale techniques with single-molecule spectroscopy [78a]. Following the seminal report

  Dedicated to Dr.J ean-RenØ Hamon on the occasion of his 60th birthday Abstract: Al igand design is proposed for transition metal nanoparticle (TMNP) catalysts in aqueous solution. Thus, at ris(triazolyl)-polyethylene glycol (tris-trz-PEG) amphiphilic ligand, 2,i su sed for the synthesis of very small TMNPs with Fe,C o, Ni, Cu, Ru, Pd, Ag, Pt, and Au. These TMNP-2 catalysts were evaluated and compared for the model 4-nitrophenol reduction, and proved to be extremely efficient.

High catalytic efficiencies involving the use of only afew ppm metal of PdNPs,RuNPs,and CuNPs were also exemplified in Suzuki-Miyaura, transfer hydrogenation, and click reactions, respectively.

Table 1 :

 1 4-NP reduction by NaBH 4 catalyzed by TMNP-2 in water at 20 8 8C.

  m À2 ]

	FeNPs	21 .3	780	1.88	1.21 10 À3
	CoNPs	22 .1	420	1.47	1.57 10 À3
	NiNPs	21 .6	720	0.30	2.69 10 À4
	CuNPs	21 .4	940	2.48	1.75 10 À3
	AgNPs	22 .2	520	7.85	6.07 10 À3
	PtNPs	0.2	1.7	01 .86	1.17 10 À2
	RuNPs	0.2	1.0	03 .15	1.26 10 À2
	PdNPs	0.2	1.5	02 4.80	0.137
	AuNPs	0.2	2.9	04 3.70	0.410

  C NMR spectra. UV-vis absorption spectra were measured with PerkinElmer Lambda 19 UV-vis spectrometer. Transmission electron microscopy (TEM) were recorded at the "Laboratoire de Chimie de Coordination" (LCC), CNRS, 205 Route de Narbonne, 31077 Toulouse Cedex, France, and at "CIC bioma GUNE, Unidad Biosuperficies, Paseo Miramon No 182, Edif "C" 20009 Donostia-San Sebastian, Spain". Size was calculated based on at least 100 NPs.

  H NMR (CDCl 3 ): δ ppm 7.68 (s, 2H), 7.63 (s, 2H), 4.39-4.32 (m, 2H), 2.57-2.48 (m, 2H).

Table 1 .

 1 CuAAC Reactions between Benzyl Azide and Phenylacetylene using Various Amounts of PEG-tris-trz-Cu I Catalyst a Reaction conditions: 0.1 mmol of benzyl azide, 0.105 mmol of phenylacetylene, and 1 mL of water. b1 H NMR conversion.c Isolated yield. d Similar yields were also obtained at 30 °C. e A similar yield (93%) was also obtained when large amounts of benzyl azide (10 mmol) and phenylacetylene (10.5 mmol) were used in 10 mL of H 2 O.

	entry	temp (°C)	Cu I (ppm)	time (h)	conversion b / yield c (%)	TON	TOF (h -1 )
	1 d	35	2000	20	100/97	485	24.25
	2 d	35	200	20	100/97	4850	242.5
	3 d	35	100	20	100/97	9700	485
	4 e,f	35	50	20	100/95	19000	950
	5	35	20	20	95/90	45000	2250
	6	35	10	24	90/86	86000	3600
	7	35	4	24	37/30	75000	3125
	8	35	0	24	0

a f

The catalyst was recycled six times under these conditions.

Table 1 :

 1 4-NP reduction by NaBH 4 catalyzed by TMNP-2 in water at 20 ℃.

Table 2 .

 2 Recycling results of Suzuki-Miyaura reactions between bromobenzene and phenylboronic acid using 0.1 mol% of PdNPs-2.

	Catalytic	1 st	2 nd	3 rd	4 th	5 th	6 th
	runs
	Yield	93%	91%	88%	87%	87%	63.6%
	RuNP-2 efficiently catalyzes transfer hydrogenation of nitrobenzene using H 2 O /
	i-propanol as the solvent at 80 ℃ in the presence of the base with only 0.01 mol% of
	catalyst at 80 ℃ for 24 h (Scheme 4 and Figure

Table 3 .

 3 Recycling results of the transfer hydrogenation of nitrobenzene using 0.1

	mol% of RuNPs-2.
	Catalytic Runs 1 st	2 nd	3 rd	4 th
	Yield	90%	85%	85%	70%

Table 4 .

 4 Recycling results of CuAAC reactions between benzyl azide and phenylacetylene using 100 ppm of CuNPs-2.

	Catalytic	1 st	2 nd	3 rd	4 th	5 th a
	Runs
	Yield	96%	86%	85%	83%	50%

Table 5 :

 5 4-NP reduction to 4-AP by NaBH 4 catalyzed by various AuNP-L (20 ℃). a

	AuNP-L	SPB (nm)	Size (nm) c	Induction time (S) K app	d

  Data are shown using 3 trz per AuNP; data in brackets are using 1 trz per AuNP.

	AuNP-5	515	2.9±0.3	0	43.7
	AuNP-6	495	2.2±0.4	40	15.2
	AuNP-5-THT 556	14.5±1	0	17.5
	AuNP-5-0℃	538	3.4±0.7	40	13.3
	a Conditions: 4-NP (1 equiv.), NaBH 4 (81 equiv.) and AuNP-L catalysts (0.2 mol%).
					)
	AuNP-2 b	527	7.3±0.5	0	2.6
		(537)	(9.5±0.7)		(2.3)
	AuNP-3 b	527	8.3±0.5	0	18.4
	AuNP-4 b	515	3.1±0.3	0	24.9
		(524)	(5.8±0.4)		(20.9)

b c

Core size (TEM) of AuNP-L.

d

Rate constant.

Thus, from the comparisons, simple trz ligands stabilize AuNPs, but only the increase of ligand denticity to two and especially three insures full AuNP stabilization. Such AuNPs form with small core sizes around 3 nm, which allows observation of the plasmonics. Interestingly, the use of amphiphilic mono-and tris-trz ligand provides micellar AuNPs in a rather similar way to amphiphilic micellar dendrimers used in efficient catalysis, but of much simpler synthesis. The 4-NP reduction in water is an excellent tool to investigate the AuNP-ligand bonding in water-soluble NPs, and indeed very high rate constant values were obtained in comparison with classical PEG-AuNPs and PVP-AuNPs.

  , have been found to be excellent, reducing the amount of Cu I catalyst to the order of 1% or less. Recently it was reported that a recyclable dendritic nanoreactor

	containing	intradendritic	triazoles	and	the
	poly(N-isopropylacrylamide-co-N-vinylimidazole) polymer promoted CuAAC
	reactions in water and in t-BuOH/H 2 O, respectively, down to the remarkable ppm
	level of Cu I catalyst under the conditions of in situ Cu 2+ reduction using NaAsc. With
	such low amounts of catalysts and exceptional efficiencies, CuAAC reactions in
	aqueous solution under mild reaction conditions effectively contributed to the pursuit
	of "green chemistry" with potential industrial applications.

Among them, nitrogen-based ligands such as polytriazoles and tris(2-aminoethyl)amine derivatives (tren)

Table 6 :

 6 Product yield upon recycling 50 ppm catalyst in the reaction condition of 0.1

	mmol benzyl azide, 0.105 mmol phenylacetylene and 1 mL water at 35℃.
	Recycling	1 st	2 nd	3 rd	4 th	5 th	6 th
	number
	Yield	95%	90%	83%	81%	75%	53%
	To investigate the underlying reason(s) for this high efficiency in the CuAAC

reactions in water using such low amounts of PEG-tris-trz-Cu I catalyst. Cu I stabilized by PEG 2000, monotrz-PEG and tris-trz-PEGwere compared with the original neat Cu I (CuSO 4 + NaAsc, A) catalyst for the CuAAC of benzyl azide and phenylacetylene in water under identical conditions (Table

Table 7 :

 7 Comparison between the crude yields (%) obtained with the Cu I , PEG-Cu I , PEG-mono-trz-Cu I , and PEG-tris-trz-Cu I catalysts in the CuAAC reaction between benzyl azide and phenylacetylene.

		Amount	2000 ppm 200 ppm	100 ppm	50 ppm
	Catalysts
	Cu I (A)	34.9	12.3	5	0
	PEG-Cu I (B)	40	12.5	5.6	2.9
	1 PEG-mono-trz-Cu I (C) 70.7	41	26.5	13.8
	3 PEG-mono-trz-Cu I (D) 91.4	79.4	66.7	34
	PEG-tris-trz-Cu I (E)	100	100	100	100
	Thus, it is confirmed that the high efficiency of these click reactions catalyzed by very
	low amounts of PEG-tris-trz-Cu I catalysts benefit from
	(i)	the chelation effect;

  -clean metal NPs on graphene oxide with good monodispersity show high efficiency in a varietry of water-based chemical reactions at ambient temperature.

	These reactions include 4-nitrophenol reduction by NaBH 4 (the standard test reaction),
	Three sections (each containing a publication) are included Sonogashira coupling, azide-alkyne 1,3-cycloaddition (click reaction) and dihydrogen
	in this chapter. production upon hydrolysis of ammonia-borane. Moreover, these efficient catalysts
	Section 3.2 demonstrates the synthesis, characterization of a recyclable RhAg can also be recycled, as exemplified in the case of RhNPs/GO catalyzed hydrolysis of
	nanocatalyst supported on reduced graphene oxide and its catalytic application as an ammonia-borane for hydrogen production.
	efficient catalyst for 4-nitrophenol reduction in water. The design of ultra-fine, highly
	efficient and recyclable heterogeneous bimetallic nanoparticles catalysts is
	Roberto Ciganda, Luis Yate and Sergio Moya. The RhAg 0.5 /rGO showed a remarkable
	reaction rate in 4-nitrophenol reduction. Moreover, the catalyst was recycled, and its
	amount was reduced to 100 ppm of RhAg 0.5 /rGO while retaining an exceptional
	catalytic efficiency.
	Section 3.3 shows the new nanocatalyst α-Fe 2 O 3 nanocluster/graphene oxide
	(α-Fe 2 O 3 /GO) for efficient Suzuki-Miyaura coupling reactions in aqueous solution
	and reduction of 4-nitrophenol (4-NP) in water employing only ppm amounts of
	catalyst. The presence of the tristrz-PEG ligand not only insured formation of α-Fe 2 O 3
	but also quantitative deposition of α-Fe 2 O 3 onto GO induced by supramolecular
	interactions. Moreover, the catalyst is recycled at least 4 times in good yields to the
	coupling products in the Suzuki-Miyaura coupling reactions.
	Section 3.4 illustrates the syntheses and catalytic applications of graphene

challenging. In this work, we report for the first time the preparation of ultrafine and monodispersed bimetallic RhAg nanoparticles that are uniformly supported on reduced graphene oxide (rGO) nanosheets (RhAg/rGO). The efficiencies of the RhAg/rGO catalysts are strongly dependent on the composition of Rh and Ag. The RhAg/rGO catalysts were characterized by various techniques including UV-vis., ICP-AES, TEM, HRTEM, STEM, EDX, and XPS, which are in collaborated with

Drs.

oxide-supported metal nanocatalysts for a variety of transition metals including both noble metals and biometals. The catalysts are synthesized using either exergonic or endergonic redox reactions between GO and the transition metal salts. These ultrafine, surface

Table 1

 1 Properties

	of the
	synthesized catalysts RhAg/	Catalysts	SPB (nm)	Size (nm)	k app (910 -3 s -1 )	k nor (s -1 g -1 )
	rGO and rate constants of 4-NP reduction by excess NaBH 4 at 20 °C	GO Ag/rGO Rh/rGO	-417 -	-2.3 2.2	-1.43 6.1	-106.9 727.1
		RhAg 0.25 /rGO	417	2.9	10.2	981.8
		RhAg 0.5 /rGO	407	2.2	14.8	1415.5
		RhAg 1 /rGO	407	2.3	12.9	1224.1
		RhAg 2 /rGO	416	2.8	10.6	998.1
		RhAg 4 /rGO	419	3.0	9.7	907.6

Table 2

 2 Comparison number of active NBNPs catalysts for the 4-NP reduction reactions being known. The k app and k nor values of RhAg 0.5 /rGO are shown to be one of the best catalysts ever obtained when compared with the NBNPs catalysts reported in the literature for 4-NP reduction (Table2). For instance, one of the best recent results were obtained by Feng's and Wang's group who reported 4-NP reduction by NaBH 4 catalyzed by Pt-Au nanodendrites supported on rGO with a remarkable reaction rate k nor = 926 s -1 g -1[56] and PtAu-nanoflowers/rGO with a reaction rate k nor = 826.7 s -1 g -1[57]. Other successful cases were that Fe@Au-ATPGO (k nor = 400 s -1 g -1 ) reported by Gupta's group[58], Pt 55 Pd 38 Bi 7 nanowires (k nor = 286 s -1 g -1 ) reported by Li's group

	of the
	catalytic performances of	Catalysts	NaBH 4 (equiv. per 4-NP)	k app (910 -3 s -1 )	k nor (s -1 g -1 )
	RhAg/rGO with other noble bi-and trimetallic NP catalysts previously reported in the literature for the reduction of 4-NP by NaBH 4	RhAg 0.5 /rGO (This work) Pt-Au dendrites/rGO [56] PtAu-nanoflowers/rGO [57] Fe@Au-ATPGO [58] Pt 55 Pd 38 Bi 7 nanowires [59]	81 23809 1429 100 33.7	14.8 3.8 12.4 1.4 4.3	1415 926 826.7 400 286
		AuPt@Au NCs/rGO [60]	1429	8.7	213
		Ni@PtNi/rGO [61]	1000	4.5	257
		Rh nanoparticles [62]	300	-	20.74
		Rh/C-500 nanosheet [63]	1000	3.1	16.5
		Ag@Au/graphene [64]	100	5.36	53.6
		Ag@Pd/graphene [64]	100	8.67	86.7
		Au-Pd/carbon spheres [65]	142.9	6.6	14.6
		Ni-Ag@rGO [66]	114.3	89	16.24
		Ag-Pt Nanowires [67]	142.9	6.93	11.55

large

Table 1

 1 Investigation of the substrate scope in the Suzuki-Miyaura reaction catalyzed by a-Fe 2 O 3 nanocluster/GO a Reaction conditions: bromobenzene (0.2 mmol), phenylboronic acid (0.3 mmol), catalyst (150 ppm a-Fe 2 O 3 ), K 2 CO 3 (0.4 mmol), EtOH/H 2 O (1 mL/1 mL), 80 1C, N 2 ,24h. b 1 H NMR conversion. c Yields of isolated products.

	Entry	R 1	R 2	Conversion b (%)	Yield c (%)
	1	H	H	100	87
	2	4-NO 2	H	100	83.3
	3	4-CHO	H	100	83
	4	4-CH 3 CO	H	100	84.5
	5	4-NH 2	H9 5	8 0
	6	4-CH 3 O	H	98	78
	7	4-CH 3	H9 0	7 5
	8	H	2-CH 3	75	51
	9	H	4-CH 3	98	82

a

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New graphene oxide supported metal nano-catalysts synthesized using redox reactions are highly efficient in water at ambient temperature for 4-nitrophenol reduction, Sonogashira coupling, azide- alkyne 1,3-cycloaddition and dihydrogen production upon hydrolysis of ammonia- borane and recyclable. Synthesis and high catalytic efficiency of transition-metal nanoparticle-graphene oxide nanocomposites

	Changlong Wang, Roberto Ciganda, Luis
	Yate, Jimena Tuninetti, Victoria Shalabaeva,
	Lionel Salmon, Sergio Moya, Jaime Ruiz,
	Didier Astruc

Table 1 .

 1 Recycling results of the 4-NP reduction using RhAg 0.5 /rGO as the catalyst.

	Catalytic runs	1	2	3	4	5
	k app	14.8	14.6	14.2	13.3	12.1
	(×10 -3 s -1 )

Table 2 .

 2 Optimization of the Suzuki-Miyaura coupling reactions. a Reaction condition: bromobenzene (0.2 mmol), phenylboronic acid (0.3 mmol), catalyst (150 ppm α-Fe 2 O 3 ), K 2 CO 3 (0.4 mmol), 80℃, N 2 , 24 h.

	Catalyst	Solvent		Conversion	Yield
	α-Fe 2 O 3 /GO	H 2 O/DMF (1mL:1 mL) 0	0
	α-Fe 2 O 3 /GO	H 2 O/ethylene	glycol	0	0
		(1mL:1 mL)
	α-Fe 2 O 3 /GO	H 2 O/EtOH (1:1, 2 mL)	100%	87%
	α-Fe 2 O 3 /GO	H 2 O/EtOH (1:1, 20 mL)	0	0
	GO	H 2 O/EtOH (1:1, 2 mL)	0 (1 st ); 0 (2 nd ); 0	0
				(3 rd ).
	α-Fe 2 O 3	H 2 O/EtOH (1:1, 2 mL)	0	0

a

Table 3 .

 3 Investigation of the substrate scope in the Suzuki-Miyaura reaction catalyzed by α-Fe 2 O 3 nanocluster/GO. a

	Entry R 1	R 2	Conversion b Yield c
	1	H	H	100%	87%
	2	4-NO 2	H	100%	83.3%
	3	4-CHO	H	100%	83%
	4	4-CH 3 CO H	100%	84.5%
	5	4-NH 2	H	95%	80%
	6	4-CH 3 O	H	98%	78%
	7	4-CH 3	H	90%	75%
	8	H	2-CH 3	75%	51%
	9	H	4-CH 3	98%	82%
	a Reaction condition: bromobenzene (0.2 mmol), phenylboronic acid (0.3 mmol),
	catalyst (150 ppm α-Fe 2 O 3 ), K 2 CO 3 (0.4 mmol), EtOH/H 2 O (1 mL/1 mL), 80℃, N 2 ,
	24 h; b 1 H NMR conversion; c yields of isolated product.

Table 4 .

 4 Performances of the catalyst RhNPs/GO-45℃ for the hydrolysis of AB with various catalytic amounts.

	Catalyst amount	Maximum	Completion time (min)	TOF
		H 2 /AB ratio		(mol H2	/
				mol catalyst • min
	0.15 mol%	3	7.75 min	258.1
	0.10 mol%	3	9.5 min	315.8
	0.05 mol%	3	24 min	250.0
	0.02 mol%	3	112 min	133.9

  49,54 The metal loading is determined by inductively coupled plasma-optical

	emission spectroscopy (ICP-AES); for instance the Ni loading in Ni NPs/ZIF-8 is 2.2
	wt%. The metal oxidation state is then identified by X-Ray photoelectron
	spectroscopy (XPS). Binding energies (B.E.) of 1021.4 and 1044.5 eV are observed
	for the 2p 3/2 and 2p 1/2 levels of the Zn 2+ ion in the ZIF-8 framework, respectively
	(Figure S5). Moreover the well-defined peaks with B.E. of 852.2 and 870.1 eV are
	detected for the 2p 3/2 and 2p 1/2 levels (Figure S6), respectively, of metallic Ni 0 in the
	Ni NPs.

Scheme 1 .

 1 17,21 Preparations of the nanocatalysts BMNP/ZIF-8.Interestingly, after the deposition of the BMNPs, the nanocatalysts BMNPs/ZIF-8 become more spherical, as exemplified by NiNPs/ZIF-8 (Figures1a and 1b). The measurements of the NP size by TEM encounters problems, however, probably due to their small sizes and lack of contrast over ZIF-8 framework. In order to release the

	BMNPs from the nanocatalysts BMNPs/ZIF-8 for direct TEM characterization, the
	ZIF-8 framework was then digested using a solution of ethylenediaminetetraacetic
	acid (EDTA) 55 in the presence of poly(vinylpyrrolidone) (PVP, Mw = 10,000) to
	stabilize the ultrasmall NPs. In this way the sizes of the BMNPs are successfully
	measured by TEM (

Table 1 )

 1 . The size of the released NiNPs is 2.7 nm, and other size distributions of FeNPs, CoNPs, and CuNPs are shown in Table 1 and in the SI (Figures S7-S10). On the other hand, nitrogen sorption experiments of the nanocatalysts show type I shape and considerable decrease of pore volume and BET surface areas (Table 1 and FigureS3). This indicates blocking of the windows of the ZIF-8 framework cavities by highly dispersed NPs within the locally distorted 145 environment or/and the location of NPs at the surface; the latter was also shown by TEM in Figure1b, for instance for NiNPs/ZIF-8.

Table 1 .

 1 Physical properties and catalytic efficiencies of the nanocatalysts.

	Sample	Size a	BET surface	Pore volume	TOF b
		(nm)	area	(cm 3 g -1 )	(mol H2 •mol cat	-1 •min -1 )
			(m 2 g -1 )
	ZIF-8	75±3	1663.3	0.6614	--
	FeNPs/ZIF-8	3.0±0.4	1313.3	0.4491	2.5
	CoNPs/ZIF-8	2.9±0.3	1313.8	0.4539	19.4
	NiNPs/ZIF-8	2.7±0.3	1324.3	0.4255	35.3/85.7 c
	CuNPs/ZIF-8	3.2±0.4	1367.3	0.4110	5.6

a TEM size.

b

Hydrolysis of AB in water at room temperature (25 ± 0.5°C), TOF = mol H2 released / (mol catalyst × reaction time (min) ).

c

TOF is obtained in the presence of 0.3M NaOH.

  concentration of NiNPs/ZIF-8; the slope is 0.98, indicating that the hydrolysis of AB catalyzed by NiNPs/ZIF-8 is first-order with respect to the catalyst concentration. On the other hand hydrolysis of AB catalyzed by NiNPs/ZIF-8 is zero-order with respect to the AB concentration, as a nearly horizontal line (slope of 0.086) is observed (FigureS13). This implies that under the present reaction conditions, AB is easily activated, and thus the possibility of the activation of AB in the rate-determining step

(RDS) is ruled out. This also is in accordance with the KIE results (vide infra). The activation energy (E a ) of AB hydrolysis, determined by measuring the time dependence of H 2 generation at various temperatures, is approximately 42.7 kJ/mol (Figure

  A KIE of1.33 is determined for deuteration at the boron site (NH 3 BD 3 ), indicating a similar dehydrogenation behavior to that of AB in H 2 O. This indicates that the absence of large KIE for hydrolysis of AB deuterated at the boron site (NH 3 BD 3 ). On the other hand, the KIE value of 2.49 is calculated according to the H 2 generation rates in ND 3 BH 3 (NH 3 BH 3 -D 2 O system), suggesting that the O-H bond cleavage of H 2 O

  It is suggested that the accumulation of too much OH -beyond the optimum level (0.3 M) could significantly reduce the beneficial effect, resulting in the decrease of the H 2 generation rate. The highest reaction rate in term of TOF is 85.7 mol H2 •mol cat-1 • min -1 with 0.3 M NaOH, showing the best activity among all the non-noble metal NP systems. This is even more efficient than noble metal NPs systems (TableS1); for instance the utilization of commercial 40 wt % Pt/C catalyst only had a TOF of55.56 mol H2 •molcat -1 • min -1 . Control experimentshows that the addition of NaOH has no effect on AB in aqueous solution in the absence of catalyst, as no H 2 release is observed, as also confirmed by the 1 H and 11 B NMR spectra.70 On the other hand, other bases such as Na 2 CO 3 and NaHCO 3 have no influence or slow down the H 2 generation rate (SI).

3 M), then decreased with higher NaOH concentration (0.4 M).

  To confirm this ion effect, other aqueous solutions of for instance NaI, NaBF 4 , NaBr, NaF, and Na 2 SO 4 were then added to the reaction media with final concentration of 0.3 M (SI). The H 2 generation rates were considerably slowed down compared with the initial reaction preformed with only NiNPs/ZIF-8, and the TOFs were10.3, 13.7, 16.2, 18.5 and 21.4 mol H2 •mol cat -1 •min -1 for NaI, NaBF 4 , NaBr, NaF and Na 2 SO 4 , respectively. Interestingly, the catalytic activities follow the order: SO 4 2-> F -> Cl -> Br -> I -, which also follows the direct Hofmeister series. Significant ion effects occurred and showed correlations with the catalytic activities obtained in the hydrolysis of AB reaction, a characteristic fingerprint of the Hofmeister effects. It is suggested that H + plays a very negative effect in the hydrolysis reaction. On the other hand, ions such as Cl -, F -, Br -et al present in the solution prefer to bind to the surface active sites of NiNPs, leaving less active surface sites available to OH -generated from

  Through the studies above, OH -facilitates the hydrolysis reaction, while H + and Cl - play negative roles in the hydrolysis of AB. At the beginning of the hydrolysis reaction, H 2 generation can be completely stopped by adding 0.3 M HCl solution, and the H 2 generation is released again by adding the same NaOH molarity. In this way, the H 2 generation is controlled. In addition, in each "on-off" cycle, a gradual decrease in the H 2 generation is also observed. Indeed the poisoning effect of H + dominates the switch off of the H 2 generation. The subsequent addition of NaOH neutralizes the HCl solution, however. The effect of NaCl production (from NaOH + HCl) was also observed in the medium, also considerably slowing down the H 2 generation (vide

	supra).

  Concluding remarks. In summary, highly dispersed ligand-free Fe NPs, Co NPs, Ni NPs and Cu NPs have been successfully synthesized using ZIF-8 as nanocatalyst template, and the highest catalytic activity for hydrogen generation upon hydrolysis of AB is shown to be that of NiNPs/ZIF-8 showing a TOF value of85.7 mol H2 •mol cat -1 •min -1 . This represents the best TOF value ever reported for noble metal-free catalysts. Detailed mechanistic investigations, especially KIE measurements, show that the RDS for AB hydrolysis is the cleavage of an O-H bond in H 2 O by means of oxidative addition of such a bond on Ni NP surfaces. Inspired by this approach, we further disclosed the ion effect in this reaction, which allowed a remarkable improvement of the catalytic performance and the controlled release of hydrogen. The principles and results obtained here may not only provide insights into the rational design of highly efficient non-noble metal-based nanocatalysts, but also demonstrate a promising step towards the application of chemical hydrogen storage materials in a fuel-cell-based hydrogen economy.

ASSOCIATED CONTENT Supporting Information. Syntheses and characterization of the nanocatalysts.

1

H NMR spectra of the products. Profiles of hydrolysis of the AB hydrolysis reactions.

  The ultrafine, surface-clean metal NPs are formed on graphene oxide with good monodispersity. These new nanocatalysts are highly efficient in water at ambient temperature. The high efficiencies and recyabilities of the nanocatalysts were exemplified in 4-nitrophenol reduction by RhNP/GO, AuNP/GO and CuNP/GO, Sonogashira coupling by CuNP/GO, PdNP/GO, and PdCuNP/GO, azide-alkyne 1,3-cycloaddition by CuNP/GO, and hydrolysis of ammonia-borane for hydrogen generation by RhNP/GO catalyst. This work shows a promising way to the rational design of efficient nanocatalysts for a large variety of chemical reactions. Heterogeneous nanocatalysts based on graphene based and metal organic framework supports are thus promising in a variety of chemical reactions, especially taking the synthetic effect, support effect and reusability into account. Thus the design of new nanocatalysts based on transition metal nanomaterials are shown here as a promising research direction due to the increasing demands of development of sustainable and green chemistry. The NP shape, size, morphology, composition, and the supports are the key parameters in the determination and enhancement of their functionality and potential applications in catalysts. Thus insights into the synthesis and characterizations of new nanocatalysts as well as the implementations by theoretical calculations will shed new light on the effective catalyst designs.

	In sum, this thesis has led to advances in development of current knowledge on
	the design, characterization, and catalytic applications of transition metal-based
	nanomaterials. The incessant search for new avenues on efficient transition-metal
	nanocatalysts benefits from the advantages of ligand design and supports, has led to
	the advent of the constructions of novel and efficient transition-metal based

Furthermore, the following work contributed to the utilization of metal organic framework-stabilized/supported non-noble metal NPs catalysts in the hydrolysis of ammonia-borane reaction. We showed the best efficiency of NiNPs/ZIF-8 nanocatalyst in term of turnover frequency in this reaction over the noble metal-free catalysts, an important achievement in terms or green chemistry and cost saving. By detailed mechanistic investigations, especially by investigating the rate-determining step in this reaction, remarkable improvement of the catalytic performance and the controlled release of hydrogen are obtained. The principles and results here may not only provide insights into the rational design of high efficient non-noble metal based nanocatalysts, but also demonstrate a promising step towards the application of chemical hydrogen storage materials in a fuel-cell-based hydrogen economy. nanocatalysts. The effectiveness of ligand design using "click" chemistry has involved the formation of triazole ligands that mildly stabilized ultrafine nanoparticles that are efficient nanocatalysts.

In spite of the rapid growth of utilization of transition metal-based nanomaterials as catalysts, problems and challenges are still remained. While theoretical and computational studies have provided insight to reactions, general chemical reactions still require considerable theoretical modeling to predict the most adequate nanocatalysts in order to achieve the best catalytic performance. In-situ characterizations would be of great value to characterize nanocatalysts and follow the chemical reactions, and to experimentally understand insights provided by theoretical calculations. Efforts in this direction should be considerable developed.

Nanomatériaux à base de métaux de transition pour la catalyse Résumé:

  La nanocatalyse à base de métaux de transition constitue un domaine prometteur pour lequel l'efficacité accrue, le caractère de chimie verte et le recyclage sont activement recherchés. Dans cet esprit, cette thèse a été dédiée à la synthèse, la caractérisation et les applications catalytiques de nouveaux nanomatériaux à base de métaux de transition. D'une part, en catalyse homogène colloïdale, des nanoparticules de métaux de transition stabilisées par des ligands amphiphiles ont procuré d'excellentes performances catalytiques en terme d'activité, stabilité et recyclabilité pour la réduction du nitro-4-phénol, le couplage de Suzuki-Miyaura, le transfert d'hydrogéné et la cyclo-addition entre un alcyne et un azoture dans l'eau. D'autre part, en catalyse hétérogène, le design, la synthèse et les applications catalytiques de nano-catalyseurs basés sur les supports de type graphène ou architectures moléculaires organiques ont également été conduits. Leurs excellentes propriétés catalytiques ont été démontrées pour la réduction du nitro-4-phénol, le couplage de Sonogashira, la cyclo-addition des alcynes avec les azotures et l'hydrolyse d'ammonia-borane avec génération d'hydrogène dans l'eau dans les conditions ambiantes.

Mots-clés : métaux de transition, nanomatériaux, catalyse, ligand amphiphile, graphène, MOF

(R = H) and the electron-poor ligand

(R = CF 3 ) gave high conversions. However, the ligand

bearing the electron-rich

Angew.C hem. Int.E d. 2016, 55,3 091 -3095 2 016 Wiley-VCH Verlag GmbH &C o. KGaA, Weinheim

016 Wiley-VCH Verlag GmbH &C o. KGaA, Weinheim Angew.C hem. Int.E d. 2016, 55,3 091 -3095

Angew.C hem. Int.E d. 2016, 55,3 091 -3095 2 016 Wiley-VCH VerlagG mbH &C o. KGaA,W einheim www.angewandte.org

DOI: 10.1021/acs.inorgchem.6b01092 Inorg. Chem. 2016, 55, 6776-6780 6777

DOI: 10.1021/acs.inorgchem.6b01092 Inorg. Chem. 2016, 55, 6776-6780 6778

DOI: 10.1021/acscatal.6b01389 ACS Catal. 2016, 6, 5424-5431 5426

DOI: 10.1021/acscatal.6b01389 ACS Catal. 2016, 6, 5424-5431 5431

Published on 12 December 2016. Downloaded by Universite Paul Sabatier on 05/01/2017 13:55:00.View Article Online

Acknowledgement

Financial support from the China Scholarship Council (CSC) of the People's Republic of China (grant to C.W.), the Universities of Bordeaux and Rennes 1 and the Centre National de la Recherche Scientifique (CNRS) are gratefully acknowledged.

Acknowledgements

Financial support from the China Scholarship Council (CSC) of the Peoples Republic of China (grant to C.W. ), the Universities of Bordeaux, Toulouse 3, Basque Country,a nd San Sebastian, the LCC (Toulouse), and the Centre National de la Recherche Scientifique (CNRS) is gratefully acknowledged.

Acknowledgements

Financial support from the China Scholarship Council (CSC) of the People's Republic of China (Grant to C.W.), the Universities of Bordeaux, Toulouse 3, the LCC (Toulouse) and the Centre National de la Recherche Scientifique (CNRS) is gratefully acknowledged.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Electronic supplementary material:

The online version of this article (doi:10.1007/s10853-017-1158-7) contains supplementary material, which is available to authorized users.

ACKNOWLEDGMENT

Record of an XPS spectrum of Ni-ZIF-8 nanomaterial from and helpful discussion with Luis Yate (CIC biomaGUNE) and financial support from the China Scholarship Council (CSC) of the People's Republic of China (grant to C.W.), the Universities of Toulouse 3 and Bordeaux, the Centre National de la Recherche Scientifique (CNRS), and CIC biomaGUNE (FP7-PEOPLE-IRSES-HIGRAPHEN Project ID: 612704) are gratefully acknowledged.

Summary

In the first chapter, a Review on "Metal-Catalyzed Azide-Alkyne "Click" Reactions: Mechanistic Overview and Recent Trends" is presented. This review is focused on the mechanistic aspects and recent trends of the metal-catalyzed azide-alkyne cycloaddition (MAAC) "click" reactions with catalysts based on various metals (Cu, Ru, Ag, Au, Ir, Ni, Zn, Ln), although Cu(I) catalysts are still the most used ones (Figure 1). The concept of "click chemistry" proposed by Kolb, Finn and Sharpless in 2001 [1] has revolutionized molecular engineering including applications to organic and medicinal

Chapter 2 An Amphiphilic Ligand for The Stabilization of Efficient Transition Metal Nanocatalysts in Aqueous Solution

Notes

The authors declare no competing financial interest.

■ ACKNOWLEDGMENTS

Financial support from the China Scholarship Council (CSC) of the People's Republic of China (grant to C.W.), the Universities of Bordeaux, Toulouse 3, the LCC (Toulouse), and the Centre National de la Recherche Scientifique (CNRS) is gratefully acknowledged.

Summary

In the second chapter, we proposed a new concept based on the design of amphiphilic ligand that mimics the functions of dendrimers to stabilize various transition metal nanoparticles in water, which are very efficient nanocatalysts with part per million (ppm) loadings for 4-nitrophenol (4-NP) reduction, "click" reaction, Suzuki-Miyaura reaction and transfer hydrogenation reaction. Moreover, we compared the stabilization of AuNPs by mono-, bis-, and tris-trz and their influence of the triazole denticity on the 4-NP reduction by NaBH 4 in water also including comparison with current polyethylene glycol 2000 (PEG) and polyvinylpyrrolidone (PVP) AuNP stabilizers.

Further, based on this tris-trz-PEG amphiphilic ligand, especially the utilization of the chelation of the triazole groups, an efficient amphiphilic "click" Cu I catalyst in water is designed. This catalyst shows high activity for CuAAC "click" reaction in water at ambient temperature with catalyst loading at only ppm levels for the synthesis of various useful functional products with medicinal, catalytic, targeting, and labeling properties.

Highly Efficient Transition Metal Nanoparticle Catalysts in Aqueous Solutions

In this first paper, we proposed a ligand design by conceptualizing the efficient amphiphilic dendrimers with tris-trz-PEG amphiphilic ligand. This tris-trz-PEG amphiphilic ligand containing three clicked triazole rings and a PEG 2000 chain is observed, because of the very small size of the CuNPs. However, CuNPs prepared in the absence of ligand, the CuNPs color was totally different and presented a SPB of 590 nm (Figure 3). Core size (TEM) of the TMNP-2.

[c] Induction time. [d] Rate constant. [e] Surface-independent rate constant.

These nanocatalysts are surprisingly efficient with only parts-per-million (ppm) metal loadings, and recyclable. For instance, the 1.5 nm-core-sized PdNP-2 with Pd(0)

surface catalyzed the Suzuki-Miyaura reaction between bromobenzene and phenylboronic acid using down to 10 ppm Pd per mol substrate (Scheme 3 and Figure 4), reaching a TON of 89000 and a TOF of 3700 h -1 in 24 h at 80 ℃ in water/EtOH mixture. Recycling the PdNP-2 catalyst in 0.1 mol% for this reaction gave yields of 87% or above up to the 5 th successive recycling run with only a slight increase of the PdNP-2 core size from 1.5 to 1.8 nm without any aggregation (Table 2). Metal-catalyzed cross-coupling carbon-carbon (C-C) bond formation has significantly advanced organic synthesis. 1 In particular, Pd-catalyzed Suzuki-Miyaura (SM) coupling has been efficiently used in numerous procedures for the construction of C-C bonds. 2 Although chemists have successfully decreased the amounts of precious Pd catalyst in such reactions, 3 alternative methodologies to accomplish a similar catalytic SM coupling using ''green chemistry'', and especially cheap biometal catalysts (for instance Fe, 4 Ni, 5 or Cu, 6 ) are highly encouraged. Nevertheless, well-defined alternative approaches most often result in the requirement of specific ligands, high catalyst loading, or hash reaction conditions and sometimes suffer from poor catalytic efficiency. Herein, we report a new heterogeneous catalytic system, a-Fe 2 O 3 nanocluster/ graphene oxide (a-Fe 2 O 3 /GO), 1, for efficient SM coupling reactions in aqueous solution and reduction of 4-nitrophenol (4-NP) in water employing only ppm amounts of catalyst.

Chapter 3 Efficient Heterogeneous Nanoparticles Catalysts

Based on Graphene Supports

The synthesis of the new heterogeneous catalyst 1 is carried out in water. It first involves addition of an aqueous solution of FeCl 3 to the pre-solubilized amphiphilic tris(triazolyl)-polyethylene glycol (tris-trz-PEG) 7 ligand in water followed by reduction using NaOH. This pre-catalyst is then deposited on GO through supramolecular H-bonding interactions between the PEG termini of the tris-trz-PEG ligand and the functional groups of the GO support, followed by filtration and drying (Scheme S1, and ESI †). The Fe content was checked by inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis indicating that 499% of the a-Fe 2 O 3 nanocluster was deposited onto GO.

The TEM images showed that a-Fe 2 O 3 nanoclusters of only 1.8 nm in size were homogeneously deposited on the edge of the GO sheets (Fig. 1a andb). EDX analysis then showed the Fe, C, N, and O signals provided by the a-Fe 2 O 3 nanocluster/GO sample (Fig. 1c). The phase structure of catalyst 1 was further characterized by HRTEM analysis showing a well-defined hexagonal shape and a lattice fringe spacing of 0.25 nm corresponding to the (110) crystallographic plane of the a-Fe 2 O 3 crystal (Fig. 1d). The oxidation state of the Fe constituent in 1 was checked by X-ray photoelectron spectroscopy (XPS). The XPS survey spectrum (Fig. S2

Conflict of interest

The authors declare no conflict of interest.

Keywords: transition-metal • nanoparticle • graphene oxide • redox reaction • catalysis

Summary

In this chapter, we mainly contribute to the rational design of nanoparticles catalysts supported on graphene based nanomaterials as efficient catalysts for a variety of chemical reactions including 4-nitrophenol reduction, Suzuki-Miyaura reaction, Sonogashira coupling, azide-alkyne 1,3-cycloaddition, and hydrolysis of ammonia-borane for hydrogen generation.

RhAg/rGO nanocatalyst: ligand-controlled synthesis and superior catalytic performances for the reduction of 4-nitrophenol

The first paper reports the preparation of ultrafine and monodispersed bimetallic RhAg nanoparticles (NPs) that are uniformly supported on reduced graphene oxide nanosheets (RhAg/rGO).

The nanocatalyst construction started with the synthesis of NPs in aqueous solution in the presence of tristrz-PEG as the encapsulating ligand and involved reduction by sodium borohydride. GO was directly added to the solution and further stirred for another 30 min, and meanwhile GO was reduced by excess of NaBH 4 to rGO. The catalyst was then aged for 3 h, washed and dried, yielding the heterogeneous RhAg/rGO catalysts (Figure 1). transfers electrons to the bimetallic catalyst surface, still increasing the charge on the key active Rh-H site (Figure 3). The reusability of the RhAg 0.5 /rGO catalyst was also investigated, and the RhAg 0.5 /rGO catalyst is reused at least five times without significant loss of reaction activity. In the fifth run, the rate constant for the 4-NP reaction was still k app = 12.1 ×10 -3 s -1 , suggesting that the RhAg 0.5 /rGO catalyst exhibits very good reusability in the reduction of 4-NP (Table 1). This efficiency is also superior to that encountered in most of the cases using noble metal based NP catalysts. Decreasing the total catalyst When the given temperature was reached, a 1 mL aqueous solution of metal precursors was then added dropwise. The mixture was allowed to further stir for 30 min, and the resulting catalyst was collected by centrifugation and washed with water, and then re-dispersed in water. The reducing nature of GO is due to the oxygenated functional groups attached to the hexagonal basal plane, further suggesting that these oxygenated functional groups (e.g.

-OH, -COOH, epoxy) on the GO nanosheets play an important role of NPs stabilizing ligands with the lone pairs of the oxygen atoms in the formation of NPs.

The ultrafine, surface-clean metal NPs are formed on GO with good monodispersity.

These new nanocatalysts are highly efficient in water at ambient temperature. The high efficiencies and recyabilities of the nanocatalysts were exemplified in Chapter 4

Metal Organic Frameworks Stabilize Efficient

Non-noble Metal Nanoparticles Catalysis

Abstract

Non-noble metal nanoparticles are notoriously difficult to prepare and stabilize with appropriate dispersion, which in turn severely limits their catalytic functions. Here using zeolitic imidazolate framework (ZIF-8) as MOF template, catalytically remarkably efficient ligand-free first-row late transition-metal nanoparticles are prepared and compared. Upon scrutiny of the catalytic principles in the hydrolysis of first row metal nanoparticles (Fe, Co, Ni and Cu, "BM") with practical efficiency and sustainability remains extremely challenging, largely due to their labile nature, complex mechanistic manifolds and low catalytic efficiencies. 26 Supported nanoparticle (NP) catalysts have shown remarkable catalytic efficiencies. It has also been found, however, that the activities were significantly influenced or/and eventually determined by the NP supports. 27-37 In this regard, metal organic frameworks (MOFs) are outstanding emerging porous nanomaterials that are advantageous compared to other conventional inorganic supports. 38-43 MOFs allow confining and stabilizing catalytically active metal NPs within their frameworks, which controls the nucleation and growth of NPs, thus preventing their aggregation and prolonging their stabilities. 44-51 Moreover, the high specific surface areas and tunable pore sizes ensured good NP dispersion, which allows exposing active sites and facilitates the accessibility of substrates to the active NP surface by reducing diffusion resistance. 44-51 On the other hand, the direct use of nanoconfinement effect by MOFs provides a facile method to prepare ligand-free and ultrafine NP/MOF nanocatalysts, which is significant but also crucial for the design of highly efficient heterogeneous catalysts. However, the comparison of the catalytic efficiencies of BMNPs using the same MOF template have not yet been disclosed.

In addition to the rational design of new nanocatalysts, insights to the mechanistic aspects of the hydrolysis reaction would be essential for the enhancement of the catalytic efficiencies of the BMNPs/MOFs nanocatalysts. The details of the reaction process of AB hydrolysis over BMNPs/MOFs nanocatalysts again have rarely been

AUTHOR INFORMATION

Corresponding Author

*Author to whom correspondence should be addressed. E-mail: didier.astruc@u-bordeaux.fr

Notes

The authors declare no competing financial interest.

Summary

Non-noble metal nanoparticles (NPs) are notoriously difficult to prepare and stabilize with appropriate dispersion, which in turn severely limits their catalytic functions.

The fourth chapter we contributed to the utilization of metal organic framework-stabilized/supported biometal NPs catalysts in the hydrolysis of ammonia-borane (AB) reaction. The ZIF-8 NPs showed high Brunauer-Emmett-Teller (BET) surface area (1663.3 m 2 g -1 ), and good thermal and chemical stabilities (Figure 1).

Hydrolysis of ammonia-borane over

We then assumed that if OH -is directly adsorbed on the surface of the Ni nanocatalyst, a bifunctional catalyst with both H and OH adsorptions should be highly desired to provoke the surface reaction. Indeed, H 2 generation rates greatly improved as compared to the one in the absence of NaOH (Figure 8), while the addition of HCl creased the reaction. The reason for the switch off of hydrogen generation comes from two aspects. One is the negative effect of H + on the self-ionization of water that suppressed the OH - formation and occupation of OH -absorption sites on the NiNP surface. The other is the ion effect, because Cl -ligands are known to limit the catalytic activity of NPs by

Conclusions and Perspectives

In this thesis, our investigations have concerned the design, characterization and catalytic applications of transition metal-based nanomaterials, specifically focusing on two aspects: The catalyst is also recoverable and can be reused without significantly loss of catalytically active NPs and activities. Furthermore, we have generalized the concept of "redox mediated synthesis" on the graphene oxide (GO)-supported metal nanocatalysts. This means that graphene oxide is used as an electron-reservoir nanomaterials that transfers electrons and eventually oxo ligands to the metals of the NPs. This recalls Basset's strategies using inorganic oxide materials as ligands of synthèse plus efficace de composes "clickés" comportant de multiples fonctions avec des quantités très minimes de catalyseur de Cu(I) dans des conditions "vertes".