Gabriel Canard
email: gabriel.canard@univ-amu.fr

Judicaelle Andeme Edzang

Dr Zhongrui Chen

Dr Matthieu Chessé

Mourad Elhabiri

Dr Michel Giorgi

Dr Olivier Siri
email: olivier.siri@univ-amu.fr

] Judicaelle

Andeme Edzang

,3-Alternate Tetra-amido-Azacalix[4]arenes as Selective Anion Receptors

Keywords: Azacalixarenes, 1,3-alternate conformation, host-guest, anions, Macrocycles

published or not. The documents may come

Introduction

The calixarene skeleton is one of the most popular scaffold used in the design of simple to very sophisticated receptors in supramolecular chemistry owing to its tunable conformation arising from the high flexibility of the macrocycle framework. [1] Consequently, calixarenes can be found in various applied research areas such as catalysis [2] or the specific delivery of drugs. [3] The large structural diversity of calixarene derivatives rely on the numerous means to change or to functionalize their skeleton. If aromatic units are often used to introduce functional groups such as in water-soluble p-sulfonatocalixarenes, [4] an important class of cavitands has emerged where noncarbon bridging atoms are incorporated into the calixarene skeleton [5] providing additional opportunities to tune the ring size, the conformation and the binding properties of the corresponding macrocycle. Among the various types of heterocalixarenes, thiacalixarenes [6] incorporating sulfurbridging atoms were the most intensively studied since their syntheses can be achieved by simple and versatile one-pot procedures. The special functionalities imparted by heteroatoms stimulated research progress in the field of other heterocalixarenes such as oxacalixarenes [7] and the emerging azacalixarenes which have been poorly investigated so far. [8] Multiple consequences and applications relying on the introduction of nitrogen-bridging atoms have to be mentioned. Several supramolecular assemblies of azacalixarenes were shown to be built on interactions involving the bridging nitrogen atoms such as hydrogen bonds [9] or Se•••N non-covalent interactions. [10] The Nalkylation is a powerful tool to build more sophisticated receptors [11] but can also be used to induce an inherent chirality [12] or to improve the macrocycle solubility. [13] Oxidation of azacalixarene derivatives can produce stable radical cations, high-spin diradicals or polycationic species since the N-atom can act as spin-bearing site and the nitrogen lone pair of each bridging atom is effectively conjugated with one or multiple neighboring aryl units. [14] This conjugation is responsible of the exclusive 1,3alternate conformation adopted by tetraazacalix [4]arenes observed in all single crystal X-ray structures of such derivatives reported so far. [8,15] NMR studies and TD-DFT calculations have shown previously that this conformation can be frozen in solution when bulky groups are born by the nitrogen atoms [16] or when appropriate substituents such as methoxy [17] or nitro groups [18] are introduced on the aryl moieties of the tetraazacalix[4]arene backbone.

Even though different synthetic strategies are now available to prepare azacalixarene derivatives, their binding properties are still rather scarce [8] and primarily concern host-guest complexes involving homoazacalixarenes [19] or cavitands incorporating heterocycles such as pyridines [20] or triazines [21] that contribute to the recognition process. As far as tetraazacalix [4]arenes lacking heterocycles are concerned, only two examples of supramolecular hostguest complexes were described and showed that their 1,3alternate conformation was suitable to bind alkali metal ions [17] or a dichloromethane molecule. [22] One would expect that this distinctive conformation can be used as a scaffold to pre-organize multiple supramolecular recognition groups such as amide ones.

We disclose here two distinctive synthetic strategies to introduce four amide groups on tetraaza[1.1.1.1]cyclophanes depending on the connection pattern between aryl units. The single crystal X-ray structures of two derivatives show, as expected, that their 1,3-alternate conformations produce a close spatial proximity between the appended amide groups allowing their involvement in a common recognition process. The anion complexation properties of one selected derivative 10 were thoroughly studied in solution and in solid state because it forms host-guest complexes precipitating in polar media (acetone, MeCN) that were characterized by several techniques including single crystal X-ray diffraction. Absorption spectrophotometric titrations show that this anion receptor displays a selectivity toward chloride anions resulting from the spatial arrangement of the four amide groups appended to the azacalix[4]arene scaffold. This contribution brings a significant advance in the applications of azacalix [4]arenes and shows that their 1,3-alternate conformation is a reliable tool to elaborate well-tailored supramolecular receptors.

Results and Discussion

Synthesis and characterization

Besides the historical Buchwald-Hartwig aryl amination reactions, [8] the formation of azacalix[4]arenes can be achieved using a catalyst-free approach based on successive nucleophilic aromatic substitutions (SNAr) [11,13,18,[21][22][23][24] between diaminobenzene derivatives as nucleophilic partners and electrophilic activated dihalogeno aryl units such as the 1,5-difluoro-2,4-dinitrobenzene 1 (Scheme 1). The use of this latter derivative is particularly efficient and has been successfully applied in the preparation of various oxa-and azacalix[4]arene derivatives. [13,18,21,22,24] Two distinctive synthetic strategies were used to introduce amide groups on tetraazacalix[4]arenes depending on the connection pattern between aryl units (Scheme 1). The tetraaza[1.1.1.1]o,m,o,m-cyclophanes 4a and 4b were prepared in a two steps procedure starting from 1 and allowing the access to unsymmetrical macrocycles. The reaction between 1,2-diaminobenzenes 2a or 2b [25] and 1 (0.5 equiv.) led to the formation of the [2+1] products 3a and 3b in good yields. Their 1 H NMR spectra (DMSO-d6) show a downfield NH at  10.15 and 10.14 ppm for 3a and 3b, respectively, in agreement with two NH•••O2N hydrogen bonding interactions that restrict the rotation of these uncyclized precursors and induce their pre-organizations towards the subsequent macrocyclization. [13,18,24c-d] 3a or 3b were then reacted with 2b in refluxing MeCN to give the tetraaza[1.1.1.1]o,m,o,m-cyclophanes 4a and 4b bearing two and four peripheral amide groups respectively. This stepwise procedure does not require chromatographic separations while the direct condensation of equimolar amounts of 1 and 2b affords a lower yield of 4b together with uncyclized oligomers that are difficult to remove. The 1 H NMR spectra (DMSO-d6) of 4a and 4b reveal that these macrocycles adopt an 1,3-alternated conformation in solution, in which the intraannular aromatic protons H1 (Scheme 1) are located inside the anisotropic shielding cone of the adjacent aromatic rings. This assumption is supported by the high-field chemical shifts at  5.05 and 5.23 ppm for H1 protons of 4a and 4b, respectively. The synthesis of compound 4c lacking amide groups has followed a previously described and analogous strategy starting from 1 and 2a. [24d] Its unprecedented single crystal X-ray structure is given here (vide infra) and compared to the one of 4b.

The preparation of the symmetrical tetra-amidotetraaza[14]m,m,m,m-cyclophanes 7-10 relies on a different two steps synthetic procedure that allows the access to numerous derivatives since the introduction of the amide groups is performed after the macrocyclization (Scheme 1). The condensation of 1 on the 1,2,4,5-tetra-aminobenzene (formed in situ by deprotonation of its tetra-hydrochloric salt 5) gives, as previously described, [26] a high yield of the tetraamino-azacalix[4]arene 6. The oxidation that usually affects electron-rich tetra-aminobenzene units [27] is here avoided through their connections with strong electronwithdrawing dinitro-aryl groups. The condensation between the tetra-amino derivative 6 with 4 to 10 equivalents of acyl chlorides in refluxing MeCN affords the tetra-amidotetraazacalix[4]arenes 7-10 with yields ranging from 32 to 87%. The 1,3-alternate conformation of 6, probed by the 1 H NMR singlet of its hydrogen atoms H1 located at  4.98 ppm in DMSO-d6, induces a spatial proximity between the four appended amine groups. Therefore, the lowest synthetic yield for 10 bearing four bulky amide groups is probably due to this geometrical orientation and remains low even if a higher excess of acyl chloride and/or a longer reaction time are used. The 1 H NMR spectra (DMSO-d6) of 7, 8, 9 and 10 support their 1,3-alternated conformations in solution through the positions of their intraannular aromatic H1 singlets chemical shifts at  5.42, 4.40, 5.33 and 5.61 ppm respectively (See the supporting information).

Host-guest species between 10 and anions A preliminary investigation using UV-vis absorption and NMR spectroscopies revealed that all the cavitands 4b-c and 7-10 interact with anions in solution. The strongest interactions, i.e. as probed by the largest variations of the UV-vis absorptions and 1 H NMR spectra, were observed using the m,m,m,m-cyclophanes derivatives 7-10. The latter derivative 10 was chosen as the subject of a comprehensive and exhaustive study because it forms stable host-guest complexes with anions that precipitate in polar media (acetone, MeCN). Addition of tetra-nbutylammonium halide or acetate salts to a solution of the host 10 in acetone led to the precipitation of the host-guest complexes that is favored by increasing with the temperature. This straightforward procedure was used to prepare the host-guest complexes 11-17 with yields ranging from 46 to 75% (Scheme 2). Inclusion complexes 11-15 were prepared starting from the tetra-n-butylammonium salts of fluoride, chloride, bromide, iodide and acetate, respectively.

1-Benzyl-4-dimethylaminopyridinium bromide [28] and 4-dimethylaminopyridinium bromide [29] were also used to evaluate the potential effect of the cation's nature in the solids 16 and 17 and compared to the solid 13 (Scheme 2). A first analysis of the selectivity of 10 in the halide series was performed through the precipitation of the solid 18 prepared by refluxing the receptor 10 in a solution containing equimolar amounts of F -, Cl -, Br -and I -(Scheme 2).

Regardless the nature of the anion, the formation of [1+1] host-guest complexes was confirmed by elemental analyses of the solid 11-17 containing between 1 and 3 water molecules (See the experimental section). This anion complexation is also supported by the presence in the ESI spectra (anion mode) of peaks for 12, 13 and 14 corresponding to the adducts [10Cl] -, [10Br] -and [10I] -, respectively (Figure S1-S5 in the supporting information). In each mass spectrum of 11-17, a peak corresponding to the deprotonated form of 10 [10-H] -can be seen, suggesting that an acid-base reaction occurs, in the gas phase, between the anion A -and the host 10 and forms the neutral acid molecule AH. No peaks corresponding to the adducts [10A] -where observed when the more basic acetate and fluoride anion are complexed while the dianionic form of 10 [10-2H] 2-is detected. Among the adducts [10A] -(A -= Cl -, Br -, I -) that can be seen on the mass spectrum of 18 (Figure S6), the highest intensity observed for [10Cl] -seemingly indicates a selectivity towards the smaller and harder anions Cl -and F -in the halide series. Further evidences were brought by the 1 H NMR spectra of diluted solution of 11-15 and 18 that were recorded and compared to the one produced by the receptor 10 upon identical conditions (Figure 1). The anioncomplexation process induces the variation of the receptor signals chemical shifts in the low fields region. Little variations are affecting the 1-3-alternate conformation of the azacalix[4]arene 10 which is retained whatever the added anions as confirmed by the chemical shift of the intraannular proton H1 decreasing from 5.61 ppm in 10 to 4.99 ppm in 12. As expected, the highest shift amplitude concerns the interacting amide protons H5 and the aromatic hydrogen atoms H4 that are located close to the complexation site (Scheme 1). Consequently, the remote hydrogen atoms H2 and H3 are only slightly sensitive to the host-guest interaction. The shift amplitude is increasing with the hardness of the anion when the bulky iodide is replaced successively by bromide and chloride. This trend is not fully retained when fluoride and acetate are interacting and produce the disappearance of the signals corresponding to acidic protons borne by the nitrogen bridging groups (H6). The close resemblance between the spectra of 12 (Cl -) and 18 is again a piece of evidence of the selectivity of 10  towards chloride anions in the halide series (Figure 1). The replacement of the ammonium counter-cation of 13 by pyridinium ions in 16 and 17 has no effect on the chemical shifts of [10Br] -showing that the cation is not directly involved in the complexation process (see the supporting information). Since the host-guest complexes between 10 and anions A -are only slightly soluble in polar media, their association constants were measured through absorption spectrophotometric titrations in an apolar solvent, i.e. 1,2dichloroethane (Figure 2 and Figures S7-S11 in the supporting information). The absorption spectrum of the host 10 is characterized by an intense absorption in the UV region (340 nm) together with a shoulder lying at a lower energy (400 nm). Previous TD-DFT calculations were performed on similar derivatives [18b] and showed that these bands originate from π-π* transitions of the electronically independent 1,5-diamino-2,4-dinitro-benzene units, those of the diamido-substituted benzene rings being centred at much higher energies. Consequently, the anion complexation process produces only little modifications of the shape and intensity of the UV-vis spectrum of the receptor. Indeed, when a solution of anions (F -, Cl -, Br -, I -, AcO -or HSO4 -) is added to a solution of 10, the intensity of the main absorption is slightly decreasing while its shoulder is slightly red-shifted. Nevertheless, the noticeable spectral amplitudes recorded along these titrations combined to the presence of four isosbestic points (Figure 2) substantiate the speciation model previously established by ESI-MS, 1 H NMR and elementary analyses and confirm the exclusive formation of [1+1] host-guest complexes involving 10 and one anion. These absorption spectrophotometric data were statistically 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 4,5 5,5 6,5 7,5 8,5 9,5 10,5 δ (ppm) 10 14 (I -)

13 (Br -) processed assuming the equilibrium (1) for the 6 different anions by using nonlinear least-squares techniques (see the experimental section in the supporting information).

12 (Cl -) 18 15 (AcO -) 11 (F -) H 6 H 2 H 5 H 4 H 3 H 1 H6 , H2 H5
10 + A - [10A -] Ka (1)
The six corresponding formation constants are listed in Table 1 and evidence a marked capacity of host 10 towards anions recognition together with a substantial size discrimination capacity. The highest association constant values were calculated to be close to 10 6 M -1 and are reached for the hardest anions F -, AcO -and Cl -while those measured for the bulkier anions such as Br -or I -are more than two orders of magnitude lower. The latter anion HSO4 - was chosen as a guest able to interact concomitantly with the four pendant amide groups of the receptor but its corresponding host-guest formation constant was only superior to that measured for iodide. As suspected before, an improved induced-fit between the receptor cavity and the chloride ion is clearly seen. The corresponding formation constant is more than two times higher than that of fluoride and more than ten times higher than the association constant measured for bromide. This unexpected selectivity probably originates from the spatial arrangement of the four interacting amide groups produced by the 1,3-alternate conformation of the azacalixarene receptor (see below).

It has to be noted that the influence of the water on the binding process of Cl -and Br -was further evaluated through new absorption spectrophotometric titrations conducted in C2H5Cl2/H2O (99.9:0.1 v/v) (Figures S12 and S13 in the supporting information). No significant effect of the water content was observed as shown by the very close binding constants that were measured under these new experimental conditions (log K10Br -= 5.2(4) in the presence of water versus log K10Br -= 5.1(2) in the absence of water; log K10Cl -= 6.3(2) in the presence of water versus log K10Cl -= 6.4(4) in the absence of water). [a] 133 181 196 220 --

[a] according to ref [30] Single crystal X-ray structures of the cavitands 4b, 4c and 10, and of the host-guest complexes 11, 13 and 15.

Diffracting single crystals were grown and were suitable for an X-ray diffraction study of compounds 4b, 4c, 10, 11, 13 and 15 (Figures 3456and Figures S14-S17 in the Supporting Information). Details of the experimental structure determinations are given in the Supporting Information with the corresponding structural data (Table S1 andS2). Two structurally similar but interacting molecules of 15 are found in the corresponding asymmetric unit while those of 4b, 4c, 10 (10a and 10b) and 13 consist of a single host or host-guest molecule. The structure of the receptor 10 is described thanks to two different single crystals grown using different experimental conditions and named 10a and 10b.

The seven different crystal structures share a common feature which is the 1,3-alternate conformation of the tetraaza[14]cyclophane backbone. This unique and stabilized conformation probably originates from the combination of two distinct features of the 1,5-diamino-2,4dinitro-benzene units that are found in each compound. The first one is the sp 2 hybridation adopted by all the nitrogen bridging atoms that are conjugated with their adjacent dinitrobenzene rings. This conjugation is corroborated by the N-C average bond length (1.36 Å) between the bridging nitrogen atoms and the electron-withdrawing dinitrobenzene ring which is significantly shorter than the one with the other aromatic unit (1.43 Å). Each nitro group is essentially planar with its attached aromatic ring as illustrated by the nitro oxygen atoms deviation from the benzene ring ranging from 0.01 to 0.43 Å and averaging 0.12 Å in the seven X-ray structures. This orientation allows the formation of intramolecular hydrogen bonds between one oxygen atom of the nitro group and the acidic hydrogen atom borne by the bridging nitrogen located at the ortho position (Figure 3) with bond lengths ranging from 2.01 to 2.06 Å and averaging 2.04 Å. These strong intramolecular hydrogen bonds are increasing the macrocycle inversion barrier and thus stabilizing the 1,3-alternate conformation. Using the classification of Tsue et al. [8a] , the conformation retained in all structures follows the clip-like type and defines two cavities between aryl groups whose sizes and shapes will be here describes using the four structural parameters d1, θ1, d2 and θ2 (Figure 3) that are listed in Table 2. d1 is the distance between the centroids of the two isolated and almost parallel benzene rings defining the angle θ1 while d2 will describe the corresponding distance between the two conjugated dinitro-benzene forming the angle θ2. The connection of the two dinitro-benzene rings by ortho-phenylenediamine moieties in 4c induces a short distance d1 of 4.80 Å between the two simple benzene rings that are almost parallel (θ1 = 4°). This close arrangement

d 1 θ 1 d 2 θ 2
(d1 = 4.62 Å and θ1 = 5°) is retained when four bulky amide groups are introduced in 4b (Figure 4). In this compound, the two adjacent amide groups of single aryl unit are forming a strong C=O•••H-N intermolecular hydrogen bond with a O•••H length of ca. 2.00 Å (Figure 4c). This interaction is reinforced by a concomitant weak C=O•••H-C hydrogen bond (Figure 4c). Therefore, in the structure of 4b only two amides NH are likely to interact with a guest. The participation of the four amide groups in a single recognition process will be facilitated if such intermolecular interactions are not enabled by a higher distance between the two amides groups born by an identical aryl unit as in the structure of its isomeric receptor 10. The modification of the substitution pattern in 10 produces a higher distance d2 of 7.33 Å between the two dinitro-benzene rings. Actually, the two different structures of 10 (10a and 10b) show that this receptor forms already host-guest complexes with two water molecules whatever the experimental conditions we chose to get diffracting single crystals (Figure 5 andS14). This affinity towards water molecules is due to the formation of a well define hydrogen bond network between the four amide groups of the receptor 10 and the two hosted molecules. Since these networks are similar in 10a and 10b only the structure of 10a will be detailed below.

The four amide groups of the receptor 10 are involved in the host-guest process through their participation in strong hydrogen bonds involving either their carbonyl CO functions or their N-H groups interacting respectively with the water hydrogen or oxygen atoms (Figure 5c). Each water molecule forms a C=O•••H-O-H hydrogen bond with one aryl unit concomitantly to a N-H•••OH2 hydrogen bond with the opposite and almost parallel aryl unit. This supramolecular network is completed by a fifth hydrogen bond between the two guest water molecules. The two remaining carbonyl groups form two intramolecular hydrogen bonds with the N-H bridging groups while the two remaining N-H amide groups interact with external acetone solvent molecules. Even if the connecting dinitro-aryl fragments are identical in 4b and 10, the complexation of two water molecules induces a higher distance between the two tetra-amido units d1 that increases from 4.80 Å in 4b to 5.05 Å in 10a. Surprisingly, this distance becomes shorter (d1 = 4.63 Å or 4.70 Å) when the acetate ion is complexed and replaces one of the two guest water molecules in the X-ray structure of 15. The corresponding asymmetric unit contains two slightly different host-guest complexes 15a and 15b that interact with each other through weak intermolecular interactions but are forming almost identical hydrogen bond networks with their guests (Figures 6 andS15). The introduction of a charged anionic guest induces a new orientation of the four amide groups that are interacting with the two guests only through hydrogen bonds involving their N-H amide groups. This reorientation is accompanied by four stabilizing hydrogen bonds formed by the four carbonyl groups and the four NH bridging groups with NH•••OC bond length values close to 2.60 Å. In the cavity, the four strong intermolecular N-H•••O hydrogen bonds are completed in the structure of 15 by a fifth hydrogen bond taking place between the two guests (Figure 6). The structures of 11 and 13 suffered from partial disorder (Figures S16 andS17). For example, the guest fluoride ion of 11 was shown to occupy four different fitted positions in the cavity while the bromide ion in 13 occupies alternatively one of the two possible positions between opposite N-H amide groups (Figures S16 andS17). Nevertheless, we are confident that the corresponding structural qualities are high enough to ensure that the corresponding host guest processes are using a similar complexation mode based on hydrogen bond networks involving the four N-H amide groups and two guests that are the anion and a water molecule. It has to be noted that the replacement of the acetate anion by a bromide or a fluoride one has no effect on the interplanar distances d1 and d2 which are roughly the same in the structures of 11, 13 and 15 (Table 2). If the higher affinity of the receptor 10 for hardest anions is the presumable result of the formation of more stable intermolecular hydrogen bonds, its selectivity towards chloride probably originates from a perfect size match between the guests and the arrangement of the four amide groups at the edges of the cavity of the azacalixarene scaffold.

Conclusions

The 1,3-alternate conformation of calix[4]arenes has been considered as the "smart" and valuable one since this conformation proved to be the basis of numerous cryptands with practical applications. [31] In the calix[4]arene family, two strategies are usually used to stabilize this particular conformation. The first one relies on the introduction of bulky substituents while the second one requires the fabrications of straps upon one or two of the resulting cavities. We described herein that such structural modifications are not required to produce, in solution, the inflexible 1,3-alternate conformation of up to six different tetraaza[14]cyclophanes. For example, heating up to 410 K DMSO solutions of 4b or 10 up to 410 K did not produce any changes of their respective 1 NMR spectra. Moreover, it has been shown that if the four amide groups of 10 are replaced by iso-propyl substituents, the corresponding inversion barrier reaches a value superior to 85 kJ.mol -1 . [18a] Consequently, the stable and "smart" 1,3-alternate conformation can be used as a scaffold to organize multiple supramolecular recognition sites. The present contribution illustrates such applications through the incorporation in the tailored receptor 10 of four peripheral amide groups that participate in a single and identical host-guest process towards anions or water molecules. This receptor proved to be particularly efficient in the bind of micromolar to submicromolar amounts of hard anions such as fluorides or acetates and showed an unexpected selectivity for chloride anions. This supramolecular recognition is due to the appearance of a well defined network of intermolecular hydrogen bonds that reaches likely an optimum arrangement when a chloride is incorporated in the macrocyclic cavity. The interaction of tetra-amide receptors 7-10 with others guests is presently investigated as well as the introductions and applications of others supramolecular recognition groups on the azacalixarene scaffold.

Experimental Section

General Remarks: All reagents were used as received. Absorption spectrophotometric titrations analyses were carried out using spectroscopic grade 1,2-dichloroethane (Merck, 99.8% or Carlo Erba, 99.8% for spectroscopy). The n-tetrabutylammonium salts (nBu4NI 98% Alfa Aesar, (nBu4N)CH3CO2 98% Alfa Aesar, nBu4NF 98% Alfa Aesar, nBu4NBr 99+% Acros Organics, nBu4NCl 98% Acros Organics and (nBu4N)HSO4 99% Acros Organics) were purchased from commercial sources and used without further purification. All solutions were protected from daylight to avoid any photochemical degradation. Flash column chromatography was performed on silica gel 60 (230-400 mesh). 1 H Nuclear Magnetic Resonance (NMR) spectra were recorded on a Bruker Avance 400 Ultrashield or on a JEOL ECS400 NMR spectrometer. Chemical shifts are given in ppm relative to residual peaks of acetone-d6 ( = 2.05 ppm) or DMSO-d6 ( = 2.50 ppm). UV-vis absorption spectra were measured with a Shimadzu UV-2401 (PC) instrument or with a Varian Cary 50. High Resolution Mass Spectrometry (HRMS-ESI) and Mass Spectrometry (ESI-MS) analyses were performed on a QStar Elite (Applied Biosystems SCIEX) spectrometer or on a SYNAPT G2 HDMS (Waters) spectrometer. These two instruments are equipped with an electrospray ionization source.

All stock solutions used for spectrophotometric titrations were prepared by weighing appropriate amount of the solid samples using a Mettler Toledo XA105 Dual Range (0.01/0.1 mg -41/120 g) and the complete dissolution in 1,2-dichloroethane was achieved using an ultrasonic bath. The concentrations of the stock solutions of 10 (~ 2.2010 -4 M) and the ntetrabutylammonium salts (~ 1.31-1.6710 -3 M) were calculated by quantitative dissolution of solid samples in 1,2dichloroethane. The absorption spectrophotometric titrations of the tetraazacalix[14]arene 10 (2.2010 -4 M) with the ntetrabutylammonium salts were carried out in a Hellma quartz optical cell (2 mm). The stock solutions of the ammonium salts were further diluted 5 to 10 times and microvolumes of the diluted solutions of nBu4NX (X = Br -, I -, F -, Cl -, HSO4 -and CH3CO2 -) were added to 500 µL of the receptor with microliter Hamilton syringes (#701 and #750). Special care was taken to ensure that complete equilibration was attained. The corresponding absorption UV-vis spectra were recorded from 220 nm to 600 nm on an Agilent Cary 5000 spectrophotometer maintained at 25.0(2) °C by the flow of a Cary Varian Dual Cell Peltier accessory. The spectrophotometric data were processed with the Specfit programs, which adjust the stability constants and the corresponding extinction coefficients of the species formed at equilibrium. Specfit [32][33][34] uses factor analysis to reduce the absorbance matrix and to extract the eigenvalues prior to the multiwavelength fit of the reduced data set according to the Marquardt algorithm. [35,36] Distribution curves of the various species were calculated using the Hyss program. [37] The intensity data of the X-ray-quality crystals of 10b, 4b and 4c were collected on a Bruker-Nonius KappaCCD diffractometer using MoKα radiation (λ= 0.71073 Å). For these compounds, data collection was performed with COLLECT, [38] cell refinement and data reduction with DENZO/SCALEPACK. [START_REF] Otwinowski | Minor in Methods in Enzymology[END_REF] The intensity data for compounds 11, 15, 13 and 10a were collected on a Rigaku Oxford Diffraction SuperNova diffractometer using CuKα radiation (λ=1.54184 Å). For these compounds, data collection, cell refinement and data reduction were performed with CrysAlis Pro (Rigaku Oxford Diffraction). The structures were solved with SIR92, [START_REF] Altomare | [END_REF] SHELXS [41] or SHELXL-2013 [41] was used for full matrix least squares refinement. The hydrogen atoms were found experimentally for compounds 11 (except for the water molecules), for the amines of compound 13, for compound 10a (except for the methyl groups) and for the water molecules of compound 10b, the remaining H-atoms were introduced at geometrical positions. All hydrogen Uiso parameters were fixed to 1.2Ueq(parent atom) for the aromatics or amines and to 1.5Ueq(parent atom) for the remaining ones. CCDC-1430290 (15), CCDC-1430291 (13), CCDC-1430292 (10a), CCDC-1430294 (11), CCDC-1430295 (4c), CCDC-1430296 (10b) and CCDC-1430297 (4b) contain the supplementary crystallographic data. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request:cif.

Organic synthesis:

1-Benzyl-4-dimethylaminopyridinium bromide, [28] 4-dimethylaminopyridinium bromide, [29] 4,5-Diamino-1,2-bis(2,2-dimethylpropionamido)benzene (2b), [25] 4 ,6,17,19tetranitro-2,8,15,21-tetraazacalix[4]arene (4c) [24d] and 4,6,16,18tetranitro-10,12,22,24-tetraamino-2,8,14,20-tetraazacalix[4]arene (6) [26] were prepared and purified according to literature procedures.

N 1 ,N 2 -bis(5-fluoro-2,4-dinitrophenyl)benzene-1,2-diamine 3a: A solution of 1,5-difluoro-2,4-dinitrobenzene 1 (2.52 g, 12.35 mmol, 2 equiv.) in THF (50 mL) was cooled with an ice-water bath before a solution of benzene-1,2-diamine 2a (666 mg, 6.16 mmol, 1 equiv.) and N-ethyldiisopropylamine (2.6 mL, 14.9 mmol, 2.4 equiv.) in THF (50 mL) was added dropwise. The mixture stirred during 3 hours at 0 °C and then during 48 hours at room temperature. The completion of the reaction was detected by a TLC on silica (AcOEt/Cyclohexane 50:50). The solvent was removed under vacuum before acetone (100 mL) was added. The resulting suspension was heated to reflux for 5 minutes and the solvent was removed under vacuum. The resulting solid was washed with EtOH (3 x 25 mL) and dried under vacuum to yield 3a (2.66 g, 5.58 mmol, 91%). M. p. 232-234 °C ; 1 H NMR (250 MHz, DMSO-d6, 25 °C):  = 10.15 (brs, 2H, NH), 8.82 (d, 4 J (H, F) = 8.0 Hz, 2H, Ar-H), 7.62-7.54 (m, 4H, Ar-H), 6.98 ppm (d, 3 J (H, F) = 14.0 Hz, 2H, Ar-H); 13 C NMR (62 MHz, DMSO-d6, 25 °C):  = 158.5 (d, 1 J (C, F) = 263.3 Hz), 147.6 (d, 2 J (C, F) = 13.3 Hz), 134.0, 129.0, 128.5, 128.1 (d, 4 J (C, F) = 0.9 Hz), 126.8, 126.2 (d, 2 J (C, F) = 10.0 Hz), 104.2 ppm (d, 2 J (C, F) = 26.9 Hz); C18H14F2N7O8 (476.30): calcd. C 45.39, H 2.12, N 17.64; found C 45.92, H 2.21, N 17.13; ESI-MS ([M+NH4] + ): 494.0; calcd. for C18H14F2N7O8 + : 494.1.

N 1 ,N 2 -bis(5-fluoro-2,4-dinitrophenyl)-4,5-bis(2,2dimethylpropionamido)-benzene-1,2-diamine 3b: A solution of 2b (154.3 mg, 0.503 mmol, 1 equiv.) and N-ethyldiisopropylamine (0.2 mL, 1.1 mmol, 2.2 equiv. ) in THF (6 mL) was added dropwise to a solution of 1 (225 mg, 1.1 mmol, 2.2 equiv.) in THF (6 mL) at 0°C. The mixture was stirred during 3 hours at 0 °C and at room temperature for 66 hours. The completion of the reaction was detected by a TLC (silica, AcOEt/Cyclohexane 50:50). The solvent was then removed under vacuum. The crude product was dissolved in a minimum amount of absolute EtOH. The solvent was then concentrated to 5% of its original volume before water (20 mL) was added. The resulting suspended solid was filtered, washed successively with hot water (10 mL), EtOH (10 mL) and Et2O (5 mL) before it was dried under vacuum to yield pure 3b (243 mg, 0.360 mmol, 72%). M. p. 256-258 °C; 1 H NMR (250 MHz, DMSO-d6, 25 °C):  = 10.14 (brs, 2H, NH), 9.07 (brs, 2H, NH), 8.96 (d, 3 J (H, F) = 8.0 Hz, 2H, Ar-H), 7.88 (s, 2H, Ar-H), 7.21 (d, 3 J (H, F)= 13.8 Hz, 2H, Ar-H), 1.33 ppm (s, 18H, C(CH3)3); 13 C NMR (62 MHz, DMSO-d6, 25 °C):  = 177.0, 158.5 (d, 1 J (C, F) = 263.2 Hz), 147.8 (d, 2 J (C, F) = 13.5 Hz), 131.0, 130.6, 128.1, 126.8, 126.2 (d, 2 J (C, F) = 9.9 Hz), 124.7, 104.3 (d, 2 J (C, F) = 26.7 Hz), 38.9, 27.1 ppm; C28H28F2N8O10 (674.57): calcd. C 49.85, H 4.18, N 16.61; found: C 49.47, H 4.29, N 16.43 4,6,17,19-tetranitro-11,12-bis(2,2-dimethylpropionamido)-2,8,15,21-tetraazacalix[4]arene 4a: A solution of 3a (1.06 g, 2.26 mmol, 1.05 equiv.) and 2b (650 mg, 2.12 mmol, 1 equiv.) in acetonitrile (30 mL) was stirred before N-ethyldiisopropylamine (1.2 mL, 6.93 mmol, 3.3 equiv. ) was added dropwise. The mixture was heated to reflux during 22 hours before it was at 0 °C for 1 hour. The resulting precipitated solid was filtered, washed successively with acetonitrile (40 mL), hot water (40 mL) and Et2O (20 mL), and then dried under vacuum to yield pure 4a (840 mg, 1.13 mmol, 54%). M. p. >300 °C ; 1 H NMR (250 MHz, DMSO-d6, 25 °C):  = 9.26 (brs, 2H, NH), 9.19 (brs, 2H, NH), 9.15 (brs, 2H, NH), 8.76 (s, 2H, Ar-H), 7.39 (s, 2H, Ar-H), 7. 33-7.22 (m, 4H, Ar-H), 5.05 (s, 2H, Ar-H), 1.27 ppm (s, 18H, C(CH3)3); 13 C NMR (62 MHz,25 °C):  = 176.7,147.3,147.2,136.1,132.5,131.1,130.9,129.0,127.4,126.7,124.1,124.1,98.8,39.0,27.1 ppm;C34H34N10O10 (742.69): calcd. C 54.98,H 4.61,N 18.86;found: C 54.91,H 4.62,N 18.64 4,6,17,19-tetranitro-11,12,24,25-tetra(2,2dimethylpropionamido)-2,8,15,21-tetraazacalix[4]arene 4b: A solution of 3b (151 mg, 0.224 mmol, 1 equiv.) and 2b (71 mg, 0.232 mmol, 1.04 equiv.) were dissolved in acetonitrile (4 mL) was stirred before N-ethyldiisopropylamine (0.1 mL, 0.578 mmol, 2.6 equiv.) was added dropwise. The mixture was heated to reflux for 46 hours and then cooled to room temperature. The solvent was removed under vacuum. The resulting solid was washed with EtOH (2 x 30 mL) and dried under vacuum to yield pure 4b (71 mg, 0.075 mmol, 34%). M. p. >300 °C ; 1 H NMR (250 MHz, DMSO-d6, 25 °C):  = 9. 21 (brs, 4H, NH), 8.91 (brs, 4H, NH), 8.78 (s, 2H, Ar-H), 7.44 (s, 4H, Ar-H), 5.23 (s, 2H, Ar-H), 1.23 ppm (s, 36H, C(CH3)3); C44H52N12O12 (940.96): calcd. C 56. 16, H 5.57, N 17.86; found: C 55.92, H 5.61, N 17.56. ESI-MS ([M+NH4] + ): 958.4; calcd. for C44H56N13O12 + : 958.4. 4,6,16,18-tetranitro-10,12,22,24-tetra(propionamido)-2,8,14,20tetraazacalix[4]arene 7: A solution of azacalixarene 6 (100 mg, 0.16 mmol, 1 equiv.) and propionyl chloride (0.12 mL, 1.3 mmol, 8 equiv.) in acetonitrile (200 mL) was stirred under argon during 1 hour at room temperature before N-ethyldiisopropylamine (0.23 mL, 1.3 mmol, 8 equiv.) was added dropwise. The mixture was refluxed overnight. The reaction was monitored by TLC (cyclohexane/ethyl acetate, 2:3, Rf = 0.2). The solvent was evaporated to dryness. The residue was triturated in water and A recrystallization from CHCl3 afforded pure 7 compound as a yellow solid (94 mg, 0.11 mmol, 87%). M. p. 225-228°C ; 1 H NMR (400 MHz, DMSO-d6, 25 °C):  = 9.50 (brs, 4H, Ar-NH-Ar), 9.32 (brs, 4H, NH-CO), 9.02 (s, 2H, Ar-H), 8.04 (s, 2H, Ar-H) 7.24 (s, 2H, Ar-H), 5.42 (s, 2H, Ar-H), 2.22 (q, 3 J (H, H) = 7.4 Hz, 8H, -CH2-CH3), 0.95 ppm (t, 3 J (H, H) = 7.4 Hz, 12H, -CH2-CH3); 13 C NMR (100 MHz, DMSO-d6, 25 °C):  = 172. 61, 147.32, 133.97, 127.92, 127.56, 126.97, 124.78, 119.56, 94.77, 28.68, 9.36 4,6,16,18-tetranitro-10,12,22,24-tetra(butylamido)-2,8,14,20tetraazacalix[4]arene 8: A solution of azacalixarene 6 (150 mg, 0.25 mmol, 1 equiv.) and butyryl chloride (0.10 mL, 1.0 mmol, 4 equiv.) in acetonitrile (50 mL) was stirred under argon during 1 hour at room temperature before N-ethyldiisopropylamine (0.17 mL, 1.0 mmol, 4 equiv.) was added dropwise. The mixture was refluxed overnight. The solvent evaporated to dryness. The residue was dissolved in CH2Cl2. The organic phase was washed with water, dried over MgSO4, filtered and evaporated under vacuum. A chromatography on silica gel (MeOH / CH2Cl2, 1:9, Rf = 0.34) followed by a crystallization from a mixture of CH2Cl2 and n-hexane afforded the pure compound 8 as a yellow solid (120 mg, 0.13 mmol, 55%). M. p. >300 °C ; 1 H NMR (400 MHz, DMSO-d6, 25 °C):  = 9.58 (brs, 4H, Ar-NH-Ar), 9.34 (brs, 4H, NH-CO), 9.01 (s, 2H, Ar-H), 7.99 (s, 2H, Ar-H) 7.24 (s, 2H, Ar-H), 5.40 (s, 2H, Ar-H), 2.24 (t, 3 J (H, H) = 6.5 Hz, 8H, CO-CH2), 1.52 (m, 8H, CH2-CH3), 0.88 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); HRMS-ESI: ([M+NH4] + ): 902.3539; calcd. for C40H48N13O12 + : 902.3540. 4,6,16,18-tetranitro-10,12,22,24-tetra(pentylamido)-2,8,14,20tetraazacalix[4]arene 9: A solution of azacalixarene 6 (100 mg, 16 μmol) and valeroyl chloride (79 μL, 0.66 mmol, 4 equiv.) in acetonitrile (150 mL) was stirred under argon during 1 hour at room temperature before N-ethyldiisopropylamine (0.11 mL, 0.66 mmol, 4 equiv.) was added dropwise. The mixture was refluxed overnight. The solvent was evaporated to dryness. The residue was dissolved in CH2Cl2. The organic phase was washed with water, dried over MgSO4, filtered and evaporated under vacuum. A chromatography on silica gel (MeOH / CH2Cl2, 1:9, Rf = 0.47) followed by a crystallization from a mixture of CH2Cl2 and n-hexane afforded the pure compound 9 as a yellow solid (112 mg, 12 μmol, 72%). M. p. >300 °C ; 1 H NMR (400 MHz, DMSO-d6, 25 °C):  = 9.56 (brs, 4H, Ar-NH-Ar), 9.31 (brs, 4H, NH-CO), 9.01 (s, 2H, Ar-H), 7.92 (s, 2H, Ar-H) 7.22 (s, 2H, Ar-H), 5.33 (s, 2H, Ar-H), 2.24 (t, 3 J (H, H) = 7.1 Hz, 8H, CO-CH2), 1.43 (m, 8H, CO-CH2-CH2-), 1.92 (m, 8H, -CH2-CH3), 0.80 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); HRMS-ESI: ([M+NH4] + ): 958.4167; calcd. for C44H56N13O12 + : 958.4166. 4,6,16,18-tetranitro-10,12,22,24-tetra(2,2dimethylpropionamido)-2,8,14,20-tetraazacalix[4]arene 10: A solution azacalixarene 6 (190 mg, 0.31 mmol) and trimethylacetyl chloride (0.38 mL, 3.1 mmol, 10 equiv.) in acetonitrile (200 mL) was stirred under nitrogen during 1 hour at room temperature before Nethyldiisopropylamine (0.55 mL, 3.1 mmol, 10 equiv.) was added dropwise. The mixture was refluxed overnight. The reaction was monitored by TLC (cyclohexane/ethyl acetate, 2:3, Rf = 0.35). The solvent was evaporated to dryness and the residue was dissolved in CH2Cl2. The organic phase was washed with water, dried over MgSO4, filtered and evaporated under vacuum. The crude residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate, 2:3) to yield 10 as a yellow solid (94 mg, 0.10 mmol, 32%

Host-guest complex

11: A solution of tetra-amidotetraazacalixarene 10 (10 mg, 10 µmol) and tetra-n-butylammonium fluoride (2.7 mg, 10 µmol, 1 equiv.) in acetone (1.5 mL) was refluxed for 24 hours. The resulting precipitate was filtered, washed with acetone and dried under vacuum to yield the host-guest complexe 11 (7.4 mg, 6.1 µmol, 60%). M. p. (dec.) >100 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C) :  = 9.02 (s, 2H, Ar-H), 7.74 (s, 2H, Ar-H), 7.14 (s, 2H, Ar-H), 5.36 (s, 2H, Ar-H ), 3.44 (t, 3 J (H, H) = 8.6 Hz, 8H, N-CH2-), 1.86 (m, 8H, N-CH2-CH2), 1.45 (m, 8H, -CH2-CH3), 1.15 (s, 36H, CO-C(CH3)3), 0.98 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); C60H88FN13O12•3H2O (1256.47): calcd. C 57. 35, H 7.54, N 14.49 found C 57.39, H 7.05, N 14,31

Host-guest complex

12: A solution of tetra-amidotetraazacalixarene 10 (18 mg, 19 µmol) and tetra-n-butylammonium chloride (5.8 mg, 21 µmol, 1.1 equiv.) in acetone (1.5 mL) was refluxed for 24 hours. The resulting precipitate was filtered, washed with acetone and dried under vacuum to yield 12 (18 mg, 14 µmol, 75%). M. p. > 300 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C) :  = 9.86 (brs, 2H, NH-CO), 9.10 (s, 2H, Ar-H), 9,08 (brs, 4H, Ar-NH-Ar), 7.36 (s, 2H, Ar-H), 7.16 (s, 2H, Ar-H), 4.99 (s, 2H, Ar-H), 3.49 (t, 3 J (H, H) = 8.6 Hz, 8H, N-CH2-), 1.83 (m, 8H, N-CH2-CH2-), 1.45 (m, 8H, -CH2-CH3), 1.13 (s, 36H, CO-C(CH3)3), 0.98 ppm (t, 3 J (H, H) = 7.31 Hz, 12H, CH3); C60H88ClN13O12•H2O (1236.89): calcd. C 58. 26, H 7.33, N 14.72; found C 58.42, H 7.39, N 14.48; ESI-MS: 939.4 ([M-H] -), 975.4 ([M+Cl] -); calcd. for C44H51N12O12 -([M-H] -) 939.5 calcd. for C44H52ClN12O12 - ([M-H] -) 975.4.

Host-guest complex

13: A solution of tetra-amidotetraazacalixarene 10 (15 mg, 16 µmol) and tetra-n-butylammonium bromide (5.65 mg, 17 µmol, 1.1 equiv.) in acetone (2 mL) was refluxed for 24 hours. The resulting yellow precipitate was filtered off, washed with acetone and dried under vacuum (14 mg, 11 µmol, 68%). M. p. > 300 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C) :  = 9.45 (brs, 4H, NH-CO), 9.13 (brs, 4H, Ar-NH-Ar), 9.11 (s, 2H, Ar-H) 7.49 (s, 2H, Ar-H), 7.21 (s, 2H, Ar-H), 5.09 (s, 2H, Ar-H ), 3.49 (t, 3 J (H, H) = 8.6 Hz, 8H, N-CH2-), 1.84 (m, 8H, N-CH2-CH2-), 1.48 (m, 8H, -CH2-CH3), 1.14 (s, 36H, CO-C(CH3)3), 0.98 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); C60H88BrN13O12•1. 5H2O (1290.35): calcd. C 55.85, H 7.11, N 14.11; found C 55.97, H 7.11, N 13.90; ESI-MS: 939.4

Host-guest complex

14: A solution of tetra-amidotetraazacalixarene 10 (7 mg, 7.4 µmol) and tetra-n-butylammonium iodide (3 mg, 8.1 µmol, 1.1 equiv) in acetone (1.5 mL) was refluxed overnight. The resulting yellow precipitate was filtered and dried under vacuum (4.6 mg, 3.5 µmol, 46 %). M. p. > 300 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C):  = 9.30 (brs, 4H, NH-CO), 9.13 (s, 2H, Ar-H), 8.72 (brs, 4H, Ar-NH-Ar), 7.84 (s, 2H, Ar-H), 7.32 (s, 2H, Ar-H), 5.47 (s, 2H, Ar-H), 3.50 (t, 3 J (H, H) = 8.6 Hz, 8H, N-CH2-), 1.81 (m, 8H, N-CH2-CH2-), 1.46 (m, 8H, -CH2-CH3), 1.17 (s, 36H, -CO-C(CH3)3), 0.98 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); C60H88IN13O12• H2O (1328.35): calcd. C 54.25, H 6.83, N 13.71; found C 54.65, H 6.91, N 13.60; ESI-MS: 939.4

Host-guest complex

15: A solution of tetra-amidotetraazacalixarene 10 (20 mg, 21 µmol) and tetra-n-butylammonium acetate (6.2 mg, 21 µmol, 1 equiv.) in acetone (2 mL) was refluxed for 24 hours. The resulting yellow precipitate was filtered off, washed with acetone and dried under vacuum to yield 15 (16 mg,

Scheme 2 .

 2 Scheme 2. Precipitation of the host-guest complexes 11-18.

Figure 1 .

 1 Figure 1. Partial 1 H NMR spectra of diluted solutions of 10-15 and 18 (in acetone-d6). The numbering scheme is detailed on Scheme 1.

Figure 2 .

 2 Figure 2. a) Spectrophotometric titration of 10 ([10] = 1.098  10 -4 M) by 0-2.5 equivalents of [(nBu4)N]Cl in 1,2-dichloroethane. b) Electronic spectra (corrected from dilution effects) of 10 and of the host-guest complex 10Cl -. c) Distribution diagram between 10 and 10Cl -during the spectrophotometric titration.

Figure 3 .

 3 Figure 3. Two views of the single crystal X-ray structure of 4c showing the structural parameters d1, d2, θ1 and θ2 (aromatic hydrogen atoms and solvent molecules are omitted for the sake of clarity). The dashed lines show the intramolecular NO2•••HN hydrogen bonds.

Figure 4

 4 Figure 4. a) and b) Two views of the single crystal X-ray structure of 4b (hydrogen atoms and solvent molecules are omitted for the sake of clarity). c) Partial view showing intramolecular hydrogen bonds involving the amide groups.

Figure 5

 5 Figure 5. a) and b) Two views of the first single crystal X-ray structure of 10 (10a) (hydrogen atoms and external solvent molecules are omitted for the sake of clarity). The guest water molecules are shown by spacefilling model. c) Partial view showing the hydrogen bond network involving the amide groups and the water guest molecules.

  Figure 6. a) and b) Two views of the first host-guest complex contained in the asymmetric unit of the single crystal X-ray structure of 15 (15a) (the ammonium cation, the hydrogen atoms and the external solvent molecules omitted for the sake of clarity). The guest acetate ion and water molecule are shown by space-filling model. c) Partial view showing the hydrogen bond network involving the amide groups and the guest anion and water molecule.

  ; ESI-MS: m/z 469.3 ([M-2H] 2-), 939.4 ([M-H] -); calcd. for C44H50N12O12 2-([M-2H] 2-) 469.2 calcd. for C44H51N12O12 -([M-H] -) 939.5.

  ([M-H] -), 1021.4 ([M+Br] -); calcd. for C44H51N12O12 -([M-H] -) 939.5, calcd. for C44H52BrN12O12 -([M+Br] -) 1021.4.

  ([M-H] -), 1067.1 ([M+I] -); calcd. for C44H51N12O12 -([M-H] -) 939.5, calcd. for C44H52IN12O12 -([M+I] -) 1067.1.

Table 1 .

 1 Formation constants of 10A -at 298 k in 1,2-dichloroethane.

	A -	F -	Cl -	Br -	I -	AcO -	HS
							O4 -
	log Ka	6.0 (4)	6.4 (4)	5.1 (2)	3.6 (2)	5.7 (2)	4.0
							(1)
	Ka X-/Ka I-	251	631	32	1	126	2.5
	Size
	(pm)

  ; ESI-MS ([M+H] + ): 675.1; calcd. for C28H29F2N8O10 + : 675.2.

  ). Ar), 9.13 (s, 2H, Ar-H), 8.47 (brs, 4H, NH-CO), 7.98 (s, 2H, Ar-H), 7.35 (s, 2H, Ar-H), 5.61 (s, 2H, Ar-H), 1.18 ppm (s, 36H, C(CH3)3); C44H52N12O12•2H2O (976.99): calcd. C 54.09, H 5.78, N 17.2; found C 54.35, H 5.31, N 17.10; HRMS-ESI: ([M+NH4] + ): 958.4166; calcd. for C44H56N13O12 + : 958.4166.

	M. p. >260 °C ; 1 H NMR (250 MHz, DMSO-d6, 25 °C) :  = 9.30 (brs,
	4H, Ar-NH-Ar), 9.00 (brs, 6H, Ar-H, NH-CO), 7.57 (s, 2H, Ar-H),
	7.41 (s, 2H, Ar-H), 5.61 (s, 2H, Ar-H), 1.09 ppm (s, 36H, C(CH3)3);
	1 H NMR (250 MHz, acetone-d6, 25 °C) :  = 9.34 (brs, 4H, Ar-NH-

Acknowledgements J.A.E gratefully acknowledges the Agence Nationale des Bourses du Gabon (ANBG) for financial support. This work was supported by the Centre National de la Recherche Scientifique and the Ministère de la Recherche et des Nouvelles Technologies (PhD grant of Z.C.). We also thank Valérie Monnier and Christophe Chendo for the analyses by mass spectrometry (Spectropole, Marseille).

d6, 25 °C):  = 9.90 (brs, 4H, Ar-NH-Ar) 9.08 (s, 2H, Ar-H), 7.72 (s,2H,7.15 (s,2H,5.34 (s,2H,3.44 (t,3 J (H, H) = 8.3 Hz, 8H, N-CH2-), 1.79 (m, 8H, N-CH2-CH2), 1.41 (m, 8H, -CH2-CH3), 1.15 (s, 36H, CO-C(CH3)3), 0.98 ppm (t, 3 J (H, H) = 7.3 Hz, 12H, CH3); C62H91N13O14• H2O (1260.49): calcd. C 59.08, H 7.44, N 14.45; found C 59.11, H 7.59, N 14.30; ESI-MS: 939.5 ([M-H] -); calcd. for C44H51N12O12 -([M-H] -) 939.5.

Host-guest complex

16: A solution of tetra-amidotetraazacalixarene 10 (20 mg, 21 µmol) and N-benzyl-4-(dimethylamino) pyridinium bromide (6.2 mg, 21 µmol, 1 equiv.) in acetone (2 mL) was refluxed for 24 hours under argon. The resulting precipitate was filtered, washed with acetone and dried under vacuum (12 mg, 10 µmol, 46%). M. p. > 300 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C):  = 9.44 (s, 4H, NH-CO), 9.13 (brs, 4H, Ar-NH-Ar), 9.12 (s, 2H, Ar-H), 8.45 (d, 3 J (H-H) = 7.9 Hz, 2H, Ar-Hpy), 7.50 (s, 2H, Ar-H), 7.44 (m, 5H, Ar-H), 7.20 (s, 2H, Ar-H), 7.16 (d, 3 J (H-H)= 7.9 Hz, 2H, Ar-Hpy), 5.56 (s, 2H, N + -CH2-), 5.08 (s, 2H, Ar-H), 3.34 (s, 6H, N-(CH3)2), 1.14 ppm (s, 36H, -C(CH3)3); C58H69BrN14O12

Host-guest complex

17: A solution of tetra-amidotetraazacalixarene 10 (12 mg, 12 µmol) and N-hydrogeno-4-(dimethylamino) pyridinium bromide (2.6 mg, 12 µmol, 1 equiv.) in acetone (1.5 mL) was refluxed for 24 hours under argon. The resulting precipitate was filtered off, washed with acetone and dried under vacuum to yield 17 (7.4 mg, 6 µmol, 50%). M. p. > 300 °C ; 1 H NMR (250 MHz, acetone-d6, 25 °C):  = 9.19 (brs, 4H, NH-CO), 9.18 (brs, 4H, Ar-NH-Ar), 9.12 (s, 2H, Ar-H), 8.29 (d, 3 J (H, H) = 7.7 Hz, 2H, Ar-Hpy), 7.6 (s, 2H, Ar-H), 7.25 (s, 2H, Ar-H), 7.10 (d, 3 J (H, H) = 7.7 Hz, 2H, Ar-Hpy), 5.25 (s, 2H, Ar-H), 3.34 (s, 6H, N(CH3)2, 1.15 ppm (s, 36H, CO-(CH3)3); C51H63BrN14O12•3H2O (1198.09): calcd. C 51. 13, H 5.80, N 16.37; found C 51.46, H 5.71, N 16.