Sophie Carenco
email: sophie.carenco@sorbonne-universite.fr

Cecile S Bonifacio

Judith C Yang

Ensemble vs. Local Restructuring of Core-shell Nickel-Cobalt Nanoparticles upon Oxidation and Reduction Cycles

Keywords: core-shell nanoparticles, reduction reactions, in situ TEM, near-ambient-pressure xray photoelectron spectroscopy

Bimetallic nanoparticles are widely studied, for example in catalysis. However, possible restructuring in the environment of use, such as segregation or alloying, may occur. Taken individually, state-of-the-art analytical tools fail to give an overall picture of these transformations. This study combines an ensemble analysis (near-ambient-pressure X-ray photoelectron spectroscopy) with a local analysis (environmental transmission electron microscopy) to provide an in situ description of the restructuring of core-shell nickel-cobalt nanoparticles exposed to cycles of reduction and oxidation. It reveals a partial surface alloying accompanied with fragmentation of the shell into smaller clusters, which is not reversible.

Beyond this case study, the methodology proposed here should be applicable in a broad range of studies dealing with the reactivity of mono-or bi-metallic metal nanoparticles.

Introduction

Understanding the behavior of bimetallic nanoparticles exposed to reactive gas is essential to the optimization of their structure and composition in several fields, such as catalysis. [1], [2] Near-ambient-pressure x-ray photoelectron spectroscopy (NAP-XPS) allows the analysis of surfaces exposed to a few mbar of gas. [3], [4] In the last decade, several studies demonstrated its relevance for the analysis of bimetallic nanoparticles prepared from colloidal synthesis. In coreshell RhPd nanoparticles, metal atoms were shown to reversibly migrate from core to surface as a function of the gas atmosphere (NO, O 2 , CO, H 2 and mixtures). [5] Such transformation was shown not to be perfectly reversible, using a comparison with RhPd single crystal. [6] Other coreshell and alloyed nanoparticles were studied, eg. PtPd and RhPt, [5], [7] RhPd with various Rh:Pd ratio, [8] and AuPd. [9] Several studies were also conducted on bimetallic nanoparticles prone to form metal oxides: CoPt, [10,11], [12] CuNi, [13] CuCo, [13], [14] FeM (M=Pt, Au, Rh), [15] etc. In the case of core-shell nanoparticles, quantitative analysis of XPS depth profiling provides the core and shell thickness, as exemplified with M-Fe 2 O 3 core-shell nanoparticles (M = Au, Pt, Rh). [16] As an ensemble measurement, NAP-XPS is relevant when the individual nanoparticles do not undergo strong changes in their shape and volume. [17] In order to verify this, other NAP-XPS studies of nanoparticles exposed to gas were backed-up by ex situ transmission electron microscopy (TEM). [7,11,15,16], [14,18] In this purpose, the nanoparticles were treated under conditions (gas pressure, temperature) comparable with these of NAP-XPS and analyzed afterwards. This methodology is efficient but has its limitations when it comes to in-depth analysis of the morphology and structural evolution of the nanoparticles. First, the nanoparticles are exposed to air between the treatment and the TEM observation: this may change the oxidation state of the surface in the case of non-noble metal nanoparticles, sensitive to oxidation. Second, the nanoparticles are cooled down to room temperature and taken out of the reactive atmosphere prior to observation: the structure observed may be a relaxed one instead of that existing under reactive conditions.

Environmental transmission electron microscopy (ETEM), as a local in situ analysis technique, provides the opportunity to study the nanoparticles under reactive atmosphere, in a pressure range that is similar to that of NAP-XPS. [19], [20] For example, it was used to follow the formation of NiGa alloy nanoparticles and there deactivation during catalytic methanol formation. [21,22] In situ imaging with simultaneous spectroscopy during reactions in the ETEM is feasible providing direct evidence of structural and elemental changes within the bimetallic nanoparticles during reactions. [23], [24] However, a general limitation of this technique is its local character: only a few nanoparticles may be analyzed in-depth.

Core-shell nanoparticles are of interest in model studies that investigate the behavior of metals within confined domains. [25] In this context, nickel-cobalt bimetallic nanoparticles were selected because they are made of abundant metals and present both magnetic and catalytic properties. At 350 °C and in the presence of H 2 , these nanoparticles reduce CO 2 in CO and methanol, instead of forming methane, as would be expected from a cobalt surface. [18] Migration of nickel from the core to the surface was evidenced during the pretreatment step of the nanoparticles, that is, during the cycles of oxidation and reduction that are typically used to clean the nanoparticles surface in the temperature range 220-270 °C. [18] Moreover, thermal properties of these nanoparticles were investigated by TEM, showing that the core-shell structure was stable up to 440 °C in the absence of reactive gas. [26] In the present paper, we combined NAP-XPS and ETEM to provide a precise account of the structural and chemical transformation occurring in core-shell nickel-cobalt nanoparticles under cycles of oxidation and reduction in the mbar pressure range. An unprecedented description of the surface oxidation state during cycles of oxidation and reduction in the mbar pressure regime is provided. At the ensemble scale, NAP-XPS demonstrates that, if nickel can be fully reduced under H 2 , this is not the case for cobalt whose average oxidation does not goes bellow oxidation state (+I). At the local scale, ETEM confirmed this finding, from both structural (selected area diffraction) and spectroscopic (electron energy loss spectroscopy) data. Moreover, TEM imaging and elemental mapping evidenced size evolution and reconstruction of the core-shell structure of the nanoparticles as a result of the gas treatments. These findings from combined ensemble and local in situ analyses dispute the ideal picture of reversible restructuring of bimetallic nanoparticles when switching between oxidizing and reducing conditions.

Experimental Section

The Ni-Co core-shell nanoparticles with sizes ranging from 25 to 45 nm were synthesized in a two-step process. [18] Ni-Co core-shell NPs were well dispersed in hexane using an ultrasonic bath for 2 minutes. NAP-XPS measurements were conducted at beamline 11.0.2 in the Advanced Light Source in Berkeley, California. [27] Two cycles of oxidation (I-O2, III-O2) and reduction (II-H2, IV-H2) at respectively 1 Torr at 220 °C and 5 Torr at 270 °C were performed (Figure 1). A sub-monolayer of nanoparticles was drop-casted on a gold foil, and gold could still be observed in the Au 4f region, which served for calibration, and Au 5p region, which overlapped with the Co 3p region.

Each XP spectrum was collected within a few minutes with the photon energy of 250 eV, 500 eV, 700 eV and 875 eV, tuned to collect electrons with various mean free paths, evaluated for the Ni 3p -Co 3p region: [START_REF] Powell | NIST Electron Inelastic-Mean-Free-Path Database -Version 1.2[END_REF], [START_REF] Seah | [END_REF], [30] 0.5 nm, 0.8 nm 1.1 nm and 1.3 nm, respectively. Resistive heating of the sample-holder button heater was used to adjust the temperature to the target. Spectrum processing was carried out using the CasaXPS software package. Shirley background was used for all spectra.

ETEM studies were performed using a dedicated ETEM FEI Titan (Center for Functional Nanomaterials, Brookhaven National Laboratory) operated at 300 keV. Similar to the XPS experiments, two cycles of oxidation-reduction reactions were conducted at 0.

Results and Discussion

Ensemble measurement by NAP-XPS

In order to analyze of the evolution of oxidation state of Ni and Co, a sub-monolayer of nanoparticles was drop-casted on a gold foil, and a set of NAP-XPS data was collected at four different photon energy (250, 500, 700 and 875 eV).

Figure 2 shows the spectra collected on the region of Ni 3p and Co 3p. Au 5p3/2 was also observed in this region. The bottom spectrum corresponds to the initial state of the nanoparticles, after introduction in the XPS chamber, while the spectra I to IV were collected after each step of oxidation or reduction. Detailed fitting procedure can be found in ESI (Table S1). For the sake of clarity, all components were plotted, included 3p 1/2 components and satellites, but only those discussed below were pointed out with colored vertical lines. Initial State. After introduction in the XPS chamber, the signal-to-noise ratio was fairly low due to the presence of carbonated ligands on the surface of the nanoparticles (Figure 2, bottom spectrum). Cobalt could be observed in an oxidized form, noted CoO x , with a peak of binding energy (B.E.) 60.2 eV (orange dotted line).

First oxidation treatment (I-O2

). The first oxidation treatment allowed burning the ligands and recovering more signal (Figure 2, spectrum II). As expected, both cobalt and nickel were observed in an oxidized form, with peaks at 60.2 eV (orange) and 66.9 eV (light green), respectively. With a photon energy of 700 eV, corresponding to an IMFP of ca 1.1 nm, the Ni:Co ratio was of 1:5 (top-right of Figure 2, I-O2). (mixed valence state). We observed that CoO was the predominant oxide after the oxidation treatment. Overall, only 20 % of the cobalt was in the Co 3 O 4 environment. Based on these Co 2p data, the average oxidation state of cobalt was 2.07 (Figure S2-C).

First reduction treatment (II-H2). Upon reduction, new XPS peaks appeared, indicating the formation of Co(0) and Ni(0), at 66.0 eV (dark green) and 58.9 eV (brown), respectively (Figure 2, II-H2). While the nickel was almost completely reduced by the treatment, cobalt oxide still represented about half of the total cobalt (Figure 2 top-right, II-H2). This was confirmed on the Near Edge X-Ray Absorption Fine Structure (NEXAFS) spectrum at Co L-edge (Figure S3 in the ESI), that shows features from both Co (778 eV) and CoO (776.5 and 781 eV). [31,32] Analysis of the Co 2p region confirmed the remaining of CoO (ca 20 % of all Co) and allowed to detect a smaller fraction of Co 3 O 4 (Figure S2-B).

Additionally, the Ni:Co ratio significantly increased to ca 1:1, confirming that nickel was able to migrate from the nanoparticles core to the near-surface, as a consequence as the reduction treatment (Figure 2 top-right, II-H2), and consistently with preliminary results reported in a previous study. [18] Second oxidation treatment (III-O2). The second oxidation treatment only slightly reduced the Ni:Co ratio down to about 2:3, while both nickel and cobalt underwent oxidation (Figure 2 topright, III-O2). Oxidation states were similar to those of step I-O2. This was confirmed by analysis of the Co 2p region (Figure S2-B). NEXAFS at Co L-edge also indicated the presence of both CoO species (identified by the shoulder at 776.5 eV) and Co 3 O 4 species (identified by the peak at 779.6 eV), although both strongly overlap.

Second reduction treatment (IV-H2).

A last reduction treatment increased the Ni:Co surface ratio to ca 3:5. The nickel could be fully reduced to a metallic state while the cobalt remained partially oxidized, as observed at the first reduction step (Figure 2 top-right, IV-H2).

Overall, relative ratio of nickel and cobalt showed that nickel was able to diffuse from the core to the shell, and the surface was slightly richer in nickel under reducing conditions.

The average oxidation states of nickel and cobalt were plotted as a function of IMFP (Figure 2 bottom-right). From the 3p region, average oxidation state was calculated assuming Ni(II) and Co(II) states for the oxides, and using the relative amounts of reduced and oxidized species showed on the top graph. For the sake of clarity, the steps I and III, where both metals are fully oxidized, were omitted.

Concerning nickel, the analysis at the initial step showed that, deeper into the core, the nickel is more reduced. This made sense, as in this case the oxidation comes from the exposure of the nanoparticles to the air during the washing treatment, at the end of the colloidal synthesis: at room temperature in air, only the very surface gets oxidized. For step (II), only nickel closer to the surface was found to be significantly oxidized. For step (IV), the nickel was metallic at all depths probed. Regarding cobalt, the situation was more complex, as purely metallic cobalt was never observed. At initial step, the whole thickness of the cobalt shell was fully oxidized, which made sense since even the nickel right beneath it was slightly oxidized. For steps (II) and (IV), no clear trend was observed in terms of depth profile, also similar average oxidation states in between 0.8 and 1.4 were observed.

Knowing that, at step (IV), the surface of the nanoparticles contains as much nickel as cobalt, one could postulate that the reduced cobalt atoms are closer to the reduced nickel, while the oxidized cobalt atoms could form islands on the particles.

Altogether, this experiment revealed a complex speciation of nickel and cobalt at oxidation state between 0 and II (and even III for cobalt). The near surface region was globally more oxidized than the inner shells. Nickel was fully reduced by H 2 and partly migrated toward the outer shells, while cobalt was only partially reduced.

In order to assess the localization of the elements within the nanoparticles as well as their morphological changes, ETEM was performed with the same sequence of oxidations and reductions.

Local measurement in ETEM

Morphology and structure

Dark-field (DF) STEM images (Figure 3-top) show the morphological changes in the nanoparticles during the two cycles of oxidation-reduction reactions. During oxidation cycle I-O2, the surface of the nanoparticles was covered with surface oxide of both nickel oxide and cobalt oxide. Interestingly, in the low pressure range used here, no hollowing of the particles was observed as a consequence of oxidation. Rather, slight volume increase was detected during the I-O2 step (Figure S4). Using image processing methods, the DF images from the oxidation and reduction steps were colorized as red and green, respectively. By overlaying the images from I-O2 and II-H2 cycles, a decrease in the overall volume of the particles was demonstrated, as a result of the reduction (Figure S4). This was accompanied by a partial fragmentation of the nanoparticles on their outer regions, which released smaller objects, observed on Figure 3 and S4 (pointed by arrows). The larger nanoparticles were mostly crystalline, as showed by SAED (Figure 3 bottom). There was no significant change in volume observed with further oxidation and reduction of the nanoparticles during III-O2 and IV-H2, respectively.

In terms of mechanical behavior, these observations suggested a dense and cohesive core surrounded by a more brittle shell, which accommodated for most of the volume changes associated during the first oxidation (expansion) and reduction (shrinking) steps. In order to correlate this to XPS data, composition and oxidation state of the outer region of the nanoparticles were analyzed in greater details.

Elemental mapping from EELS

The local elemental composition of the nanoparticles was analyzed by acquiring EELS spectrum images of the Co L edge and Ni L edge. In the initial state and during the cycles of oxidation and reduction, the nickel-rich core and the cobalt-rich shell were observed.

The EELS spectrum images provided the distribution of Ni and Co during the reactions.

During the first reduction step (II-H2), clusters of particles were observed on the surface of the nanoparticles (Figure 4). This correlates with the STEM image and SAED analysis during II-H2 in Figure 3. Further analysis of the EELS maps identified the clusters as Co-rich (Figure S5). The spectrum map during IV-H2 step in Figure 4 shows green pixels, representing Ni, on the surface of the nanoparticle, suggesting rearrangement of the core-shell structure.

EELS analysis of the composition in the near-surface is presented on the right panel of Figure 4. The oxygen ratio is always fairly high (around 50 %) as it comes not only from the nanoparticle surface oxide, but also for the underlying grid. It will not be further discussed. As expected, on the shell region nickel was detected in much lower amounts than cobalt. However, the atomic fraction of nickel increased to 4.5 %, 4.9 % and 12.0 % from the initial state to the II-H2, the III-O2 and the IV-H2 steps, respectively. Further analysis of the spectrum maps showed an increased fraction of nickel in the shell from II-H2 to IV-H2 (Figure S6). These observations confirmed the partial migration of Ni from the core to the shell. They also indicated that the evolution of Ni:Co ratio observed by XPS (Figure 2) were mostly a surface phenomenon, and that full alloying of the nanoparticles was not occurring under these fairly soft reaction conditions.

Oxidation State

Oxidation state was evaluated by two methods: through the identification of crystalline phases by SAED analysis and through the Co L 3 /L 2 ratio measured by EELS.

Figure 3 shows the changes in the nanoparticles along with the SAED. As a first result, SAED showed that metallic nickel was present at all stages in the nanoparticles. Because it was not always observed by XPS (a surface-sensitive spectroscopy), it had to be mostly in the core of the nanoparticles. Moreover, metallic cobalt was never observed. We proposed this is a consequence of both the lesser amount and smaller size of the corresponding domains on the surface, yielding broader and weaker SAED spots, which were thus not detected in these measurements.

During oxidation cycle I-O2, the surface of the nanoparticles was covered with both nickel oxide and cobalt oxide. SAED analysis resulted to identification of the oxide species as NiO, CoO and Co 3 O 4 (I-O2 in Figure 3b). These observations were consistent with XPS and NEXAFS results.

After reduction cycle II-H2, the surface of the nanoparticles was covered with clusters of particles (12-17 nm in size). SAED spots for Co 3 O 4 were absent, as well as the weaker ones from CoO (111). This confirms the partial reduction of cobalt oxides, observed by XPS. This process was essentially repeated upon steps (III) and (IV) even though Co 3 O 4 was not clearly observed anymore. This was once more consistent with XPS, which showed the coexistence of Co(0) and CoO at step (III), the cobalt being overall slightly more reduced than at step (I).

Complementarily with the SAED study, the oxidation states of cobalt during the reaction cycles were determined from the L 3 /L 2 intensity ratio calculated from the acquired Co L 2,3 ionization edges (Figure S7). The average EEL spectra at the shell was obtained and the branching ratios calculated using the method described by Zhao et al. [33] where 6 Gaussian peaks (3 for L 3 and 3 for L 2 edges, see Figure S8 for details of analysis) were used to fit the L 3 and 3 for L 2 edges. The L 3 /L 2 intensity ratio was subsequently calculated from the ratio of the integrated areas underneath the Co L 3 and L 2 absorption edges, respectively. To identify the phase of the cobalt oxide, EELS data were acquired from of Co 3 O 4 and CoO powders and the same fitting method was applied. In the case of metallic Co, the metallic Co EELS data from Zhao et al. was analyzed and used as reference for the metallic Co phase. The calculated L 3 /L 2 intensity ratios were compared in Figure 5 During the I-O2 step, the L 3 /L 2 ratio is expected to be equal or higher than the L 3 /L 2 ratio at room temperature and under vacuum. Such discrepancy can be attributed to residual oxygen inside the microscope before the reaction cycle and possibly from data analysis. The accuracy of L 3 /L 2 EELS intensity ratios is subject to processing parameters during data analysis such as continuum background fitting, widths of integration windows, etc. [34] As a result, variation of the absolute L 3 /L 2 intensity ratios from the reference sample is observed. However, the relative changes observed in this study are consistent and impart reliable evidence for the variation in 3d transition metal oxidation states. [35], [36] In fact, the convexity of the Co L 3 /L 2 ratio correlated with valence state of Co in the XPS results from II-H2 to IV-H2 steps in Figure 5 (left). In both XPS and EELS results, the CoO phase is present during the oxidation-reduction steps, in contrast with the Co 3 O 4 phase. This may be explained by the preferential formation of CoO at the nanometric scale compared to the bulk. [37], [38]

Conclusion and outlooks

The unique combination of ensemble measurement (NAP-XPS with depth profile, NEXAFS) with local measurements (ETEM, DF-STEM, SAED and EELS) allows drawing a full and detailed picture of the behavior of Ni-Co core-shell nanoparticles exposed to oxidation and reduction cycles.

(1) the nickel-rich metallic core of the nanoparticles was mostly not affected by this procedure, as showed by its chemical and structural stability.

(2) the surface of the nanoparticles was mechanically brittle, possibly due to volume increase upon oxidation. Partial fragmentation of the surface layers was not a reversible process.

(3) both techniques confirm the trend of nickel enrichment as a consequence of the cycles, although there is a slight pullback upon re-oxidation at step (III). This pullback may tentatively be attributed to the lower Gibbs free energy of CoO vs. NiO. [23] (4) both techniques confirmed that reduction of cobalt was only partial at steps (II) and (IV), and slightly more advanced at the later one. At this stage, there is no indication regarding further morphological and compositional evolution of the nanoparticles upon further cycling. However, the lack of reversibility observed within the first two cycles suggests that deeper changes may occur over time ad cycling in a real setup.

Increase of overall free energy (from surface oxidation and mixing of metals) should be the driving force for these irreversible changes.

With the combined XPS and TEM studies, the ensemble and local elemental composition and oxidation states were obtained, allowing for an understanding of the stability limitations of the Ni-Co core-shell NP structure. None of the two techniques, albeit multifaceted, may have provided a satisfactory picture of the overall transformation of the nanoparticles, hence on the nature of active sites. Moreover, all the transformations described above occurred under fairly gentle conditions (below 280 °C and 5 Torr), compared with these typically used in hydrogenation processes, eg. CO and CO 2 hydrogenations, or in oxidation catalysis. Thanks to the growing number of ETEM and NAP-XPS instruments worldwide, we believe that the methodology presented in this article should find an application in a broad range of studies dealing with the reactivity of mono-or bi-metallic metal nanoparticles.

2

 2 Torr at 220 °C and 0.3 Torr at 270 °C. Longer reaction times in the ETEM were used (Figure 1) to compensate for the lower allowable ETEM reaction pressures in comparison to the NAP-XPS reaction pressures (0.2-0.5 Torr in the ETEM vs. 1-5 Torr in the NAP-XPS). Electron energy loss spectroscopy (EELS), dark field (DF) Scanning TEM (STEM) images and selected area electron diffraction (SAED) were recorded during oxidation or reduction reactions in the ETEM.

Figure 1 :

 1 Figure 1: The four stages of treatment (I to IV) in NAP-XPS and ETEM. Pressures are

Figure 2 :

 2 Figure 2: NAP-XPS of NiCo nanoparticles during cycles of oxidation and reduction. (Left)

Figure 3 :

 3 Figure 3: (Top) STEM-HAADF from step (I) to step (IV). (Bottom) SAED of the

Figure 4 :

 4 Figure 4: Dark field STEM images (top) and corresponding spectrum images for Ni L edge

  (right) to identify the phase of the cobalt oxide during each reaction cycles in the ETEM study. The Co L 3 /L 2 ratio was decreasing for the reference spectra for CoO, Co and Co 3 O 4 , respectively. By comparing the experimental results to the reference spectra, the surface of the nanoparticle has undergone a change in valence states between Co 2+ and Co 0 during the oxidation-reduction reactions in the ETEM. The decreasing and increasing L 3 /L 2 ratio exemplified the reduction and oxidation cycles, respectively.

Figure 5 :

 5 Figure 5: Oxidation state of cobalt at the surface of the nanoparticles during the treatments.

Acknowledgements

The Advanced Light Source is acknowledged for beamtime on beamline 11.0.2. Hendrik Bluhm is acknowledged for his expertise with NAP-XPS at beamline 11.0.2. S.C. acknowledges CNRS, Sorbonne Université and Collège de France. C.S.B. and J.Y. acknowledge Sara Mills for the help in EELS data processing, Dr. Eric Stach and Dr. Huolin Xin from Center for Functional Nanomaterials (CFN) at Brookhaven National Lab for the ETEM data acquisition. The ETEM work was done in CFN, BNL supported by the Office of Basic Energy Sciences of the US Department of Energy Contract No. DE-SC0012704.


Philippe Merloz

Jocelyne Troccaz

Hervé Vouaillat

Christian Vasile

Jérôme Tonetti

Ahmad Eid

Stéphane Plaweski

Fluoroscopy-based navigation system in spine surgery

Keywords: Computer Aided Surgery, Virtual Fluoroscopy, Surgical Navigation

come

Fluoroscopy-based Navigation System in Orthopaedic Surgery

MERLOZ Ph [START_REF] Coetzee | Exposure of surgeons-in-training to radiation during intramedullary fixation of femoral shaft fractures[END_REF], TROCCAZ J (2), VOUAILLAT H (1), VASILE Ch (1), TONETTI J (1), EID A (1), PLAWESKI S (1).

(1) University Department of Orthopaedic and Trauma Surgery ; CHU A. Michallon ; BP 217, 38043 Grenoble cedex 09 (France)

Tel : + 33 4 76 76 55 93 ; Fax : + 33 4 76 76 52 18 ; Pmerloz@chu-grenoble.fr

(2) Equipe GMCAO -Laboratoire TIMC/IMAG (Université Joseph Fourier -CNRS UMR 5525). Institut d'Ingénierie de l'Information de Santé Faculté de Médecine -38706 La Tronche cedex -France Tel: +33 (0)4 56 52 00 06 -Fax: +33 (0)4 56 52 00 55 Secr: +33 (0)4 56 52 00 07 ; Jocelyne.troccaz@imag.fr http://www-timc.imag.fr/gmcao et http://www-timc.imag.fr/Jocelyne.Troccaz Introduction :

Mobile fluoroscopic device is an integral part of the standard equipment used in orthopaedic surgery to provide real-time feedback of bone and surgical tool positions. One of the disadvantages of this technique include the need for continuous radiation exposure for realtime visual control. For instance, in some specific surgical procedures such as distal locking in standard closed intra-medullary nailing of the femur and tibia, it is well known that this procedure is time-consuming and causes much irradiation to the patient and to the surgical team. In this exemple the surgeon's direct exposure to radiation varies from 3.1 to 31.4 min per procedure and 31 to 51 % of the total irradiation is spent on distal locking alone [START_REF] Coetzee | Exposure of surgeons-in-training to radiation during intramedullary fixation of femoral shaft fractures[END_REF][START_REF] Levin | Radiation exposure to the surgeon during closed interlocking intramedullary nailing[END_REF][START_REF] Skejdal | Interlocking medullary nails -radiation doses in distal targeting[END_REF].

In clinical practice, mobile fluoroscopy device is not only used for distal locking in standard closed intra-medullary nailing for femur and/or tibial fractures, but also for many others surgical procedures. For instance, three other classical procedures are well known to cause much radiation : insertion of pedicle screws in spine surgery for trauma, scoliosis and degenerative instabilities ; osteosynthesis of intra -extra capsular femoral neck fractures and ilio-sacral joint fixation for the treatment of ilio-sacral joint disruption. This paper describes a computer-assisted surgical navigation system based on fluoroscopic X-ray image calibration and 3D optical localizers in order to reduce radiation exposure while increasing accuracy and reliablility of the surgical procedure for implant insertion. We will describe the surgical technique used for pedicle screw placement in spine surgery, before a brief report on other techniques.

II. Material and Methods :

A three-dimensional optical localizer (Polaris system ; Northern Digital ; Ontario ; Canada) is used to track the position of surgical tools, patient reference and C-arm image intensifier (OEC Medical system ; Courtabeuf ; France) within the region of the operating table (Fig. 1).

Each component is equipped with passive markers that give the position of three distinct tools (patient reference frame ; surgical tools : pointer, sharp tip probe, bradawl and drill guide ; C-arm), with the help of the three -dimensional optical localizer.

Fluoroscopic images are usually distorted. This is due to three factors: the planarity of the image intensifier input screen, the insufficient rigidity of the c-arm and the surrounding magnetic field [START_REF] Chakraborty | Image Intensifier Distortion Correction[END_REF][START_REF] Hoffmann | Pincushion correction techniques and their effects on calculated 3D positions and imagning geometries[END_REF]. To correct image intensifier distortions and calibrate images, a calibration grid (equipped with passive markers) is attached rigidly to the input screen of the image intensifier (Fig. 2). The aim of the calibration process is to learn the mapping between image pixels and the "physical" surgical space, so that the computer can generate a virtual projection of the surgeon's tool axis onto the calibrated X-ray views. The calibration device is fixed to the image intensifier and contains radio-opaque elements arranged on two parallel plates. Radio-opaque elements who are included in the lower plate are used to correct the image distortions and these of the upper one to detemine the x-rays source position (Fig. 2).

To determine the x-ray source position, passive markers are fixed on the calibration device and the three-dimensional optical tracking system is used to localize the fluoroscopic imaging device (Fig. 2,3).

The correction of original images can be effected thanks to the radio-opaque elements of the lower plate projected onto the images (Fig. 4).

We describe here the surgical technique using virtual fluoroscopy in spine surgery for pedicle screw fixation. In spine surgery, the complications associated with misplaced pedicle screws are mostly neurological or vascular. Previous study of surgical procedures have shown a significant rate of incorrect placement of pedicle screws ranging from 15 % to 40 % [START_REF] Ph | Computer Assisted Spine Surgery[END_REF][START_REF] Foley | Virtual fluoroscopy[END_REF].

Virtual fluoroscopy is one of the solution to increase safety of screw placement.

The patient is settled in prone position and the surgeon perform a posterior approach. In a first step, the surgeon attaches the dynamic reference frame to the patient's bone of interest (in this case : spinous process of the vertebra to be operated on) and aligns the optical localizer's cameras optimally (Fig. 3). In a second step, the surgeon acquires one X-ray view, just to calibrate the C arm. In a third step, two single X-ray views from A-P and lateral positions are acquired within the area who has to be operated on (Fig. 5). Data are passed on to the workstation computer (Fluologics system, Praxim, France) (Fig. 1). After calibration of the acquired X-rays by the computer, the fluoroscope is turned off and removed from the operating field.

Finally, the calibrated views are displayed on the workstation screen. A computer-generated projection of the surgeon's surgical tool is also displayed in each view. This is equivalent to its representation under conventional constant fluoroscopic control. A real-time navigation in several views is possible simultaneously (Fig. 6). The feasibility of this technique for lumbar pedicle screw insertion was assessed through cadaver and clinical trials by Foley et al. [START_REF] Foley | Virtual fluoroscopy[END_REF].

Twenty six patients underwent posterior osteosynthesis with pedicle screws to correct fractures and degenerative instability of the thoraco-lumbar spine by using virtual fluoroscopy (26 patients ; vertebra level: T10 to L5 ; 140 screws). In the same time, twenty six patients underwent the same surgical procedure (26 patients ; vertebra level: T10 to L5 ; 124 screws) by using conventional technique (surgical classical procedure to insert pedicle screws, and immediate fluoroscopic control). Evaluation of screw placement in every cases was done by using plain X rays and post operative CT scan, with the help of an independant examiner.

Irradiation data and intervention duration were collected during conventional and computeraided procedures.

III. Results :

In the computer-aided group (26 patients ; vertebra level: T10 to L5 ; 140 pedicle screws) the results showed that the technique provided much better safety and accuracy than manual insertion (Fig. 7). A percentage of cortex penetration of less 5 % (7 of 140 pedicle screws) occured for the computer assisted group with an average below or equal to 2 mm in five cases. In the two other cases the cortex penetration was slightly higher than 2 mm without complications. A percentage of penetration of 13 % (18 of 124 pedicle screws) occured for the non computer assisted group (26 patients ; vertebra level: T10 to L5 ; 124 pedicle screws)

with an average below or equal to 2 mm in four cases, and with an average below or equal to 3 mm in 14 cases . In the two groups there were no neurologic complications.

The virtual fluoroscopy shows clearly that the system provides better accuracy and safety than conventional fluoroscopy. When we compare irradiation data with the same data collected during conventional procedures we can say that virtual fluoroscopy reduces significantly radiation exposure time by the 1 / 3 ratio (3,5 sec. on the average for each procedure with virtual fluoroscopy versus 11,5 sec. on the average for each procedure with conventional technique). The operative time with virtual fluoroscopy is slightly greater than the one recorded with conventional techniques (10 minutes on the average for one vertebra level -two screws -with conventional procedure versus 11,9 minutes on the average for one vertebra level -two screws -with virtual fluoroscopy). The main reasons for time increase are the following : setup, reference frame attachment, data acquisition, significant learning curve.

IV. Discussion :

This paper describes a computer-assisted surgical navigation system based on fluoroscopic Xray image calibration and 3D optical localizers. Currently available computer-assisted orthopaedic systems are generally based on 3D image data sets that are acquired preoperatively with a Computed Tomography (CT) scanner [START_REF] Ph | Computer Assisted Spine Surgery[END_REF][START_REF] Ph | Computer-Assisted Pedicle Screw Insertion[END_REF]. A fluoroscopy-based computer system can be seen as a complement or an alternative to the use of a CT-based computer system (CT scans provide full 3D image data, not fluoroscopic images). The advantages over CT-based systems are twofold : instant availability without preoperative preparation (no CT acquisition required) and up-to-date image data of patient anatomy (X-ray images used for navigation are acquired at the beginning of surgical procedure) [START_REF] Ph | Computer Assisted Spine Surgery[END_REF][START_REF] Foley | Virtual fluoroscopy[END_REF][START_REF] Ph | Computer-Assisted Pedicle Screw Insertion[END_REF]. As compared to standard fluoroscopy, the fluoroscopy-based computer system allows real-time navigation in several X-ray projections simultaneously, with the fluoroscope turned off and removed from the operating field and reduces significantly radiation exposure of both patient and surgical staff. Finally, we believe that this system can also greatly improve on surgical accuracy and safety of other applications in orthopaedics [START_REF] Kahler | Computer-Assisted Iliosacral screw placement of compared to standard fluoroscopic technique[END_REF][START_REF] Kahler | Virtual fluoroscopy : a tool for decreasing radiation exposure during femoral intramedullary nailing[END_REF].

Fluoroscopy is commonly used in some other surgical procedures such as distal locking in closed intra-medullary nailing for femur and/or tibial fractures, osteosynthesis of intra -extra capsular femoral neck fractures and ilio-sacral joint fixation for pelvic ring disruption. With conventional procedure, each of them represents a real clinical challenge with technical complexity and potentially leading to additional pitfalls and complications and necessitates some specific technical details.

For instance, percutaneous distal locking is a good challenging step in standard closed intramedullary nailing of the femur. Many complications can be described with distal locking procedure : inadequate fixation, malrotation, bone cracking, cortical wall penetration, bone weakening due to multiple or enlarged screw holes and distal fragment rotation if the drill is not perfectly aligned with the hole axis in the nail. Improving screw placements, virtual fluoroscopy leads to reduce the complication rate [START_REF] Kahler | Virtual fluoroscopy : a tool for decreasing radiation exposure during femoral intramedullary nailing[END_REF][START_REF] Hazan | Computer-assisted image-guided intramedullary nailing of femoral shaft fractures[END_REF]. Taking into account technical aspects, when using virtual fluoroscopy for distal locking in closed intra-medullary nailing of the femur the reference frame has to be fixed onto the distal part of the femur (metaphysis).

Ilio-sacral joint screwing is another difficult clinical challenge, and some intra and postoperative complications can occured, such as inadequate fixation or cortical wall penetration [START_REF] Kahler | Computer-Assisted Iliosacral screw placement of compared to standard fluoroscopic technique[END_REF][START_REF] Lange | Pelvic ring disruptions with symphysis pubis diastasis : indications, technique and limitations in anterior internal fixation[END_REF]. If it's so, an extra osseous course in the anterior part of the sacrum, can lead to injure the lumbo-sacral root of the ischiatic nerve. Safety and accuracy can be improved thanks to the "virtual" multiplanar guidance, while radiation exposure can be also significantly reduced [START_REF] Gautier | Accuracy of computer-guided screw fixation of the sacroiliac joint[END_REF][START_REF] Schep | Positioning of sacroiliac screws with fluoroscopy based navigation technique[END_REF][START_REF] Stöckle | Navigation assisted by image conversion. An experimental study on pelvic screw fixation[END_REF][START_REF] Grutzner | Virtual fluoroscopy in accute treatment of pelvic ring disruptions[END_REF]. To optimize ilio-sacral joint screwing when using virtual fluoroscopy the reference frame is generally attached to the iliac crest, and the procedure in most of the cases can be performed percutaneously.

Inadequate fixation and cortical wall penetration are the two main complications when performing osteosynthesis of intra -extra capsular femoral neck fractures. Once again, the use of virtual fluoroscopy demonstrated that this technique could increase safety and accuracy in osteosynthesis and the procedure is generally performed with a minimal invasive approach.

In this example (trochanteric and femoral neck fractures), the reference frame has to be fixed onto the proximal part of the femur (trochanteric area).

Regarding the basic principle of CAS systems, i.e. multi-modal data registration, the authors wish to focus the attention on some new technologies that are currently under development or being tested, which they believe will soon replace the existing techniques in the next generation of CAS systems, mainly because of their increased accuracy and efficiency, but also because of an easier implementation in the OR [START_REF] Tonetti | Clinical results of percutaneous pelvic surgery. Computer assisted surgery using ultrasound compared to standard fluoroscopy[END_REF]. The recent coming out of 3D fluoroscopic devices [START_REF] Desbat | Minimally Invasive Interventional Imaging for Computer-Assisted Orthopaedic Surgery[END_REF][START_REF] Grutzner | First clinical experience in inherent registration techniques with mobile 3D fluoroscopy for matching free navigation. Preliminary report of a new method for intraoperative navigation[END_REF][START_REF] Ritter | Direct Marker-free 3D Navigation with an Isocentric Mobile C-Arm[END_REF] should allow surgeons to dispose of 3D models without the need for any data registration at all. This new technology should allow percutaneous implant (screw) placement to be performed in a very near future [START_REF] Tonetti | Clinical results of percutaneous pelvic surgery. Computer assisted surgery using ultrasound compared to standard fluoroscopy[END_REF].

V. Conclusion :

A reduction in outliers (screw misplacement) was consistently associated with the use of computer-assisted techniques, regardless of the navigation system used. Many studies indicate that the consistency of screw placement achieved with computer-assisted techniques results in a corresponding consistency in clinical functional outcomes. This paper emphasizes the Fig. 3 : To determine the x-ray source position, passive markers are fixed on the calibration device and the three-dimensional optical tracking system is used to localize the fluoroscopic imaging system. One can see the reference frame fixed onto the spinous process of the vertebra to be operated on ( -----------), and the markers on the calibration grid.

Fig. 4 : The correction of original images (on the left) can be effected thanks to the radio-opaque elements of the lower plate projected onto the images (on the right).

Fig. 5 : Two single X-ray views from A-P and lateral positions are acquired within the area who has to be operated on (here a lumbar vertebra).

Figures and Legends :

  Figures and Legends :

Fig. 1 :

 1 Fig.1 :A three-dimensional optical localizer (A) is used to track the position of surgical tools, patient reference and C-arm image intensifier (B) within the region of the operating table. One can see the computer under the 3D localizer.

Fig. 2 :

 2 Fig.2: The calibration grid is fixed to the image intensifier and contains radio-opaque elements arranged on two parallel plates. Radio-opaque elements who are included in one of the plate (picture) are used to correct the image distortions.

Fig. 6 :Fig. 7 :

 67 Fig.6: A computer-generated projection of the surgeon's surgical tool is displayed in each view. A real-time navigation in several views is possible simultaneously.

Fig. 1 :

 1 Fig. 1 : A three-dimensional optical localizer (A) is used to track the position of surgical tools, patient reference and C-arm image intensifier (B) within the region of the operating table.

Fig. 2 :

 2 Fig.2: Navigated tools and the markers. Each tool is equipped with passive markers (white spots can be seen). From the left to the right, one can see the reference frame (fixed onto the spinous process of the vertebra to be operated on), the pointer, the bradawl and the drill guide.

Fig. 3 :

 3 Fig.3: The calibration grid is fixed to the image intensifier and contains radio-opaque elements arranged on two parallel plates. Radio-opaque elements who are included in one of the plate (picture) are used to correct the image distortions.

Fig. 4 :

 4 Fig.4: Two single X-ray views from A-P and lateral positions are acquired within the area who has to be operated on (here a lumbar vertebra).

Fig. 5 :

 5 Fig. 5 : A computer-generated projection of the surgeon's surgical tool is displayed in each view. A real-time navigation in several views is possible simultaneously.

Fig. 6 :

 6 Fig. 6 : Evaluation of pedicle screw placement : L1 lumbar fracture (screws on T12, L1 and L2) (A : conventionnal AP view ; B : conventionnal lateral view) (C : CT scan lateral view ; D : CT scan axial view on T12). The two screws on T12 are perfectly inserted in the pedicle.

importance of examining the incidence of outlier functional results in the evaluation of computer-assisted surgery. Cost, additional time, and learning curve might very well be compensated by the significant outlier reduction.


Xavier Frogneux

Ferenc Borondics

Stéphane Lefrançois

Florian D'accriscio

Clément Sanchez

Sophie Carenco
email: sophie.carenco@sorbonne-universite.fr

Surprisingly high sensitivity of copper nanoparticles toward coordinating ligands: consequences for the hydride reduction of benzaldehyde

Functionalized copper nanoparticles are widely used as catalysts; however, identification of the catalytically active species remains a challenge. In this study we investigate hydride-assisted reduction reactions with special focus on the structural evolution of copper nanoparticles in the presence of phosphine and nitrogen-based ligands. These compounds are commonly used as stabilizing agents, therefore are important in the context of other catalytic reactions as well. In particular, we investigate the case of tri-n-butylphosphine. Our findings show that ultrasmall nano-objects are formed as key intermediates to produce catalytically active species in the hydrosilylation of benzaldehyde into the corresponding silyl alcohol. Moreover, we found that the strength of the hydride donor is essential for the formation of the active catalysts. Therefore, this work unveils the previously overlooked high sensitivity of copper nanoparticles toward coordinating ligands in the context of catalysis.

Introduction

Among the variety of metallic nanoparticles (NPs), copper NPs are made from a cheap and abundant metal, allowing scale-up in industry. They feature specific properties such as a plasmon band in the infrared range, high electrical and thermal conductivity and interesting catalytic performances, e.g. for methanol production. 1 In particular, they catalyze the chemical reduction of various moieties (carbonyl derivatives, alkynes, alkenes, nitro-compounds). [2][3][4][5][6][7][8][9][10][11] Nonetheless, due to their high sensitivity to oxidation, fabrication routes for Cu NPs are not as well-documented as for Ag or Au NPs. In order to obtain pure Cu(0) nanoparticles, colloidal syntheses are of interest as they allow working in an organic solvent with a large variety of ligands, enabling the tuning of the capping species at the surface of the nanoparticles. [12][13][14][15][16][17] The reactivity of the nanoparticles can be controlled by the interaction between the ligand and the metallic center. [18][19][20][21][22] In some cases, ligands can be detrimental to the integrity of the NPs due to the leaching of metal-ligand complexes into the medium, as it has been thoroughly studied for Pd-based catalytic systems. [23][24][25] In the case of Cu-based NPs, leaching has been observed in some reactions but, so far, leached species were not considered as potential catalytic species.

26-29

In the present study, Cu NPs were produced by colloidal synthesis in oleylamine, following a previously reported procedure. 15 Their surface was characterized under air-free atmosphere by FTIR, revealing the presence of unexpected Noleylacetamide moieties at the nanoparticles surface. Hydrosilylative reduction of benzaldehyde was performed with the Cu NPs as catalysts and the formation of products was monitored in situ using an attenuated total reflectance infrared cell especially designed for air-sensitive nanoparticles.

We showed that the addition of a second ligand (tri-nbutylphosphine, 1,8-diazabicyclo [5.4.0]undec-7-ene or oleylamine) was modulating the catalytic activity of the nanoparticles. While all these tested ligands induced a significant leaching of copper species into the solution from the nanoparticles, only the tri-n-butylphosphine provided active catalytic species. Moreover, such species were only formed with strong enough hydride donors such as phenylsilane. Leaching of copper from the nanoparticles was not sufficient by itself to allow the catalytic reduction of benzaldehyde. Rather, formation of active species demanded an adequate hydride source. This may explain why the facile leaching of copper in the presence of coordinating ligands was overlooked so far in many works using copper nanoparticles as catalysts.

Results and Discussion

Surface capping agent of copper nanoparticles prepared with oleylamine

Copper nanoparticles were prepared by reducing [Cu(acac) 2 ] in oleylamine (OAm) at 250 °C for 2 h under inert atmosphere (see experimental section). 15 The NPs were isolated with four cycles of washing and centrifugation and dried under a N 2 flow. X-ray diffraction on powder (XRD) confirmed the fcc-Cu(0) phase with a crystallite average size of 13 nm according to the Debye-Scherrer formula. Transmission Electron Microscopy (TEM) showed the presence of polydisperse nanoparticles of 35 ± 10 nm in diameter (Figure 1A,B and S1 in SI). The identification of surface species stabilizing the copper nanoparticles was performed by Fourier-transformed infrared spectroscopy (FTIR) in a tailor-made air-tight Teflon cell designed for measurement in attenuated total reflection (ATR) mode (see experimental section). In the glovebox, a solution of the nanoparticles was drop-casted on a silicon single-crystal wafer. The wafer was inserted and sealed in the cell, allowing measurements under inert conditions. Figure 1C shows FTIR of the copper nanoparticles compared with pure oleylamine, which was expected to be the main capping ligand around the nanoparticles. As expected, alkyl chains were detected on the nanoparticles through the C-H vibration bands at 2922 and 2852 cm -1 and the C-H deformation mode at 1465 cm -1 slightly shifted at 1455 cm -1

for the copper nanoparticles. The characteristic signals of the free amino group of oleylamine (ν(N-H) at 3318 cm -1 and δ(N-H) at 1558 cm -1

) could not be found on the nanoparticles spectrum; and no -OH group was detected in the 3000-4000 cm -1 area (see SI, Figure S4). Moreover, the alkenes absorption bands (ν(C=C-H) at 3005 cm -1 and ν(C=C) at 1650 cm -1 ) were also not observed on the spectrum.

Noticeably, the spectrum of the NPs layer showed an absorption band at 1728 cm -1 that could indicate the presence of a carbonyl moiety. As a complementary analysis, 1 H NMR analysis was performed on the supernatant of the reaction (prior to washing steps) (see SI, Figure S2). A multiplet at 5.35 ppm was detected, corresponding to alkene moieties. The absence of the corresponding IR band on the NPs could indicate either that the ligands coordinated to the nanoparticles did not contain alkene moieties, or that these moieties were in strong interaction with the surface. Moreover, based on the 1 H NMR spectrum, it is clear that the amino group of oleylamine, which should have appeared as a triplet at 2.64 ppm (N-CH 2 ) and a signal at 1.1 ppm (N-H 2 ), is completely absent. Further, the presence of a singlet at 1.97 ppm indicated a possible condensation of oleylamine with an acetylacetonate fragment, consistent with the presence of a ν(C=O) band in FTIR. The supernatant of the reaction was also analyzed by gas chromatography coupled to a mass spectrometer (GC-MS). It showed the presence of a major product of mass 309 g.mol -1 .

In relation with the bands detected in the FTIR spectrum, this was attributed to N-oleylacetamide (CH 3 -CO-NH-R, with R as the alkyl chain of oleylamine), formed during the heating process of the NPs synthesis from the condensation of oleylamine with an acetyl fragment coming from the decomposition of acetylacetonate. 30,31 H from this N-H moiety was detected as a "free" species by 1 H NMR of the supernatant by a broad signal at 2.60 ppm (Figure S2), although the N-H vibration was not observed by FTIR for the species coordinated to the surface. It should be noted that this product was also detected in the analogous synthesis of nickel nanoparticles, although in that case it was not the major product. 31,32 Altogether, an unexpected surface ligand, N-oleylacetamide, formed during the synthesis of the nanoparticles and acted as the main native capping ligand on the surface of the nanoparticles.

Influence of tri-n-butylphosphine on the reactivity of copper nanoparticles for the reduction of benzaldehyde

The copper-catalyzed reduction of benzaldehyde was investigated in solution, without and with additional tri-nbutylphosphine. Tri-n-butylphosphine was selected, among commercial phosphines, as a coordinating ligand, expected to improve the colloidal stability of the nanoparticles in solution, as observed with other metal nanoparticles, [33][34][35] and also for its ability to modify the electronic properties of the copper nanoparticles.

The nanoparticles were engaged in the reduction of benzaldehyde by hydrosilylation using phenylsilane in tetrahydrofuran (THF) (Scheme 1). Hydrosilanes represent a very convenient hydride source for the reduction of carbonyl compounds since they can be used in very mild conditions, limiting the formation of over-reduction products and allowing chemoselective and/or asymmetric reactions. 36 The silicon moiety can then be easily removed in the presence of fluoride to recover the alcohol. 37 Among them, phenylsilane is considered a strong hydride donor, and was selected for the first series of experiment.

First attempts using the nanoparticles as prepared showed no catalytic activities. Tri-n-butylphosphine (P(n-Bu) 3 , 1 equiv. vs. Cu) was added as a co-catalyst: a dark-reddish suspension formed, suggesting an improved colloidal stability of the nanoparticles. As a result the complete reduction of benzaldehyde was observed within 1 h at room temperature (RT), using 0.6 mol% of copper vs. benzaldehyde. The 1 H NMR spectrum of an aliquot of the mixture revealed the complete conversion of benzaldehyde into the corresponding silylated alcohol (Table 1, entry 1, vide supra). Noticeably, upon the addition of phenylsilane and benzaldehyde to suspension of Cu NPs/P(n-Bu) 3 , strong bubbling and heating of the solvent was immediately observed. Bubbles came from the dehydrogenation of the phenylsilane (producing H 2 , detected by 1 H NMR), which is a competitive reaction.

Scheme 1 -Cu-catalyzed hydrosilylation of benzaldehyde with phenylsilane

In order to understand the role of the phosphine, the reaction was reproduced in the air-tight FTIR cell: the nanoparticles were drop-casted on the silicon wafer as before, and a THF solution containing benzaldehyde, phenylsilane and P(n-Bu) 3 in molar ratio 1:0.4:0.006 (identical to the ratio used in the standard protocol) was added onto the nanoparticles layer.

Figure 2A shows the series of spectra collected immediately before (first spectrum) and after addition of the solution (ca. 0.1 mL), over 2000 s. Several bands were observed on the initial spectrum, coming from THF (1969 cm

-1 , 1460 cm -1 , 1365 cm -1 , 1289 cm -1
), benzaldehyde (1704 cm -1

, two bands at 1597 and 1585 cm -1 , 1310 cm -1

; blue dots) and phenylsilane (2157 cm -1 , red dot). After addition of the reaction mixture in the cell, the FTIR spectra were dominated by the absorption peaks of the solvent and reactant. Product formation was detected through the appearance of bands at 1594 cm -1 , 1497 cm -1 and 1379 cm -1 (Figure 2A, green dots). Figure 2B shows the time evolution of the integrated intensities of the bands at 1704 cm -1 (ν(C=O)) and 2156 cm -1 (ν(Si-H)). Their fast decrease indicated that the reaction in the cell was completed within 500 s. Moreover, the monotonic decrease of the benzaldehyde and phenylsilane concentration (Figure 2B) suggested no induction time at the time-scale of a few tens of seconds. As a control experiment, injection of the reaction mixture deprived of P(n-Bu) 3 lead -as expected -to no reduction of the benzaldehyde, although a partial decomposition of the silane was observed (see SI, Figure S5). As a partial conclusion, the combination of both the Cu NPs and P(n-Bu) 3 was essential to observe a catalytic activity (Table 1, entries 1-4). The absence of an induction time at a 10 s time scale, as well as the immediate release of H 2 observed experimentally upon addition of the benzaldehyde into the nanoparticles suspension, indicated that the active catalytic species were formed from Cu NPs and P(n-Bu) 3 prior the addition of the reactants. This phosphine effect is not specific to P(n-Bu) 3 as other phosphines (tricyclohexylphosphine, triphenylphosphine) or the diphosphine (1,2bis(diphenylphosphino)benzene showed comparable reactivities after 15 min of reaction time (see ESI, Table S1). The more sterically hindered tri-tert-butylphosphine and the tridentate phosphine 1,1,1tris(diphenylphosphinomethyl)ethan proved to be very poor ligands for this catalytic reaction. [Cu(acac)2] + P(n-Bu)3 >99%

Reaction conditions: in a 10 mL closed tube, catalyst (0.6 mol%, 0.016 mmol) in THF (5 mL), P(n-Bu)3 (0.6 mol%, 0.016 mmol), PhCHO (5 mmol), hydride source (6 mmol). NR: no conversion of benzaldehyde.

In order to gain insights into the catalyst nature, the activity of nanoparticles was compared with that of copper complexes.

The initial [Cu(acac) 2 ] compound used for the nanoparticles synthesis proved to be an inefficient catalyst for this reaction (Table 1, entry 5). However, in the presence of 1 equiv. of P(n-Bu) 3 , the blue solution quickly turned yellow to dark in seconds, suggesting the formation of Cu NPs (Figure S13), showed the same reactivity than the nanoparticles for benzaldehyde reduction ( The observations described above using nanoparticles as catalysts (e.g. the brightening of the red color at the addition of the phenylsilane) were reminiscent of the formation of copper hydride species stabilized by phosphine ligands. 39,40 In fact, among the variety molecular metallic complexes known to promote hydrosilylative reduction of carbonyl derivatives, 36,41,42 Cu(I) and Cu(II) complexes proved to be potent candidates because of the formation of copper hydride species, stabilized by electron-rich phosphines. [43][44][45][46][47] However, the in situ formation of nanoparticles or clusters, such as Stryker's reagent, is rarely discussed 38 whereas they can be active in various reactions. 1,48,49 Thus, we investigated the nature of the active species and the possibility of leaching in the current reaction.

Description of the active catalytic species

Leaching is a recurring issue when using NPs in catalysis, as the generated solvated metal complex or clusters, in our case Cu, could as well be catalysts for the reaction. Thus, we performed a leaching test, using a less reactive hydrosilane, TMDS (1,1,3,3-tetramethyldisiloxane), in order to stop the reaction at a partial conversion after 15 minutes (Scheme 2). Benzaldehyde was reacted with TMDS in the presence of Cu NPs/P(n-Bu) 3 as catalyst for 15 min (Scheme 2A). Then, half of the crude (B) was centrifuged at 10,000 g for 25 min whereas the other half (dark red) was kept intact (D). 50 The colorless supernatant (C) was carefully collected from (B) and PhSiH 3 was added, yielding a light yellow solution. Similarly, PhSiH 3 was added to flask (D), yielding a bright red solution (E). In both cases, PhSiH 3 addition was quickly followed by the formation of bubbles and a slight heating of the solution, meaning that active copper complexes were still present in the nanoparticle-free solution (C). After 15 min of stirring, 1 H NMR of both solutions showed similar conversion of benzaldehyde into the silylated alcohol. According to TEM, the initial Cu NPs (see Figure 1A) were already etched in numerous smaller NPs (< 5 nm) after addition of the TMDS (Scheme 2D) and their morphology was even farther from the starting one after addition of PhSiH 3 (Scheme 2E). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) of the supernatant (C) revealed that it contained about 5% of the initial copper: homogeneous copper species and/or small clusters were produced from the NPs via a leaching phenomenon. It is to be noted that the system {[Cu(acac) 2 ] + P(n-Bu) 3 } is also efficient at the loading of the detected species by ICP in the supernatant (approx. 0.03 mol%). At this point, two hypotheses can be considered: (i) Cu NPs act as a copper source to release catalytically active copper hydride molecular complexes/clusters or (ii) both Cu NPs and leached copper hydride species are catalytically active.

The leaching was further studied by analyzing clean Cu NPs/P(n-Bu) 3 suspensions in THF after 18 h at RT. Cu NPs/P(n-Bu) 3 in a 1:1 ratio already showed a non-negligible amount of small Cu NPs compared to the initial ones (<5 nm versus 40 nm) (Scheme 3A). Increasing the quantity of phosphine in solution led to even more etching of the Cu NPs. At 250 equiv. of P(n-Bu) 3 , only nanoscaled species smaller than 5 nm were found on the TEM grid. Noticeably, the same effect occurred by replacing the phosphine by a typical ligand for copper complexes, DBU (1,8-diazabicyclo[5.4.0]undec-7ene), [51][52][53] or even by oleylamine 13 (Scheme 3B). However, neither of these suspensions of leached copper nanoparticles showed catalytic property for the reduction of benzaldehyde with phenylsilane. This means that the formation of leached nanoscaled species was not sufficient to produce catalytically active species. Rather, the phosphine was required as a cocatalyst. To identify more precisely the active catalytic species, copper species resulting from the phosphine presence were analyzed by electrospray-ionization mass spectroscopy (ESI-MS). These species were produced by stirring Cu NPs (3 mg) for 24 h in pure P(n-Bu) 3 (3 mL). After washing cycles with THF and centrifugation, the powder was redispersed in THF as a red suspension. Copper species with nuclearity of 1 to 5 stabilized by P(n-Bu) 3 were detected: e.g. Cu(PBu 3 ) 2 (m/z = 469), (PBu 3 ) 2 Cu 5 (CN) 4 (m/z = 825) (see SI, Figure S14,15). Larger species could not be detected by our experimental setup but were observed by TEM (Scheme 3A).

In order to determine if the leaching was a cause of the nanoscale of initial copper nanoparticles, the reaction was also explored with an ultrapure copper foil (purity >99.99%) as the copper species. The copper foil alone (ca. 50 mg) was not able to catalyze the reduction of benzaldehyde with phenylsilane at 20 °C after 18 h. However, in the presence of P(n-Bu) 3 in a catalytic amount (0.6 mol%), the colorless solution turned light yellow and the septum of the flask was swollen, indicating the formation of gaseous H 2 . The 1 H NMR analysis revealed that ca. 20% of benzaldehyde was converted into various silylated species. Additionally, the 31 P{

1 H} NMR showed drastic decrease and broadening of the signal of free P(n-Bu) 3 (at -32 ppm) (see SI, Figure S19), indicating a possible coordination of the phosphine in cluster-type complexes. The control reactions were performed without Cu foil or without P(n-Bu) 3 , resulting in no conversion of benzaldehyde. At this point, it appeared that the source of copper was not critical regarding the existence of leaching.

The generation of copper-hydride species is a key step in the copper-catalyzed reduction of carbonyl compounds (Scheme 4)

43,54

and appears to be related to the nature of the coordinating ligands (P(n-Bu) 3 , OAm, DBU). So far, we demonstrated that several coordinating ligands were able to generate leached species from the Cu NPs but only phosphinestabilized copper species were able to act as catalysts for the hydrosilylative reduction of benzaldehyde (Scheme 4, right).

Copper-hydride species require stabilization, which is usually done with phosphines or N-heterocyclic carbenes. 48,55 Among the three ligands studied here, we propose that only P(n-Bu) 3 stabilizes them properly. To test this hypothesis, different hydride sources were investigated in the presence of P(n-Bu) 3 (Scheme 4).

Influence of the hydride source on the activity of the copper catalyst

Various hydride sources were tested for the reduction of benzaldehyde, in similar conditions as previously (0.6 mol% of Cu NPs/P(n-Bu 3 ), RT, 18 h). Compared to the other reductants, ammonium formate was also more detrimental to the integrity of the nanoparticles, according to TEM observation after the catalytic test (SI, Table S2).

Finally, bubbling H 2 in the system did not result in any conversion of benzaldehyde (entry 13). Noticeably, the reduction of benzaldehyde was highly dependent on the hydride choice. This means that the formation of phosphinestabilized copper species was not sufficient to obtain catalytically active species. Thus, the adequate combination between the right ligand and a strong enough hydride donor seems mandatory to reach a catalytic activity.

Conclusions

This work highlights the ligand sensitivity of the applications of Cu NPs in catalytic reduction reactions and reactivates the question of the homogeneous or heterogeneous state of the catalytically active species, as it has been the case for Pt-based catalysts for the hydrosilylation of olefins. [60][61][62] In the presence of a phosphine (such as P(n-Bu 3 )), these NPs proved to be active for the reduction of benzaldehyde in the presence of a strong enough hydride source. The activity of this system is based on the rapid partial leaching of the NPs, which act as a copper reservoir, releasing phosphine-stabilized copper species that seem to be the catalytically active species. Leaching was not systematically providing active catalytic species: rather, these should present a suitable ligand (phosphine) in combination with a suitable hydride source (silylated or not).

We propose this as the reason why many catalysis studies on ligand-stabilized copper nanoparticles do not report leached molecular species as the active catalytic species, although these may form in the reaction medium. From a more fundamental perspective, model studies of the interaction of phosphines with planar copper surfaces (e.g. single-crystals) may inform on the elementary steps of the leaching process.

Figure 1

 1 Figure 1 -(A) TEM of the Cu NPs. (B) Histogram of diameters for Cu NPs. (C) FTIR spectrum of Cu NPs layer (top) and oleylamine (bottom) measured under inert atmosphere.

Figure 2 -

 2 Figure 2 -Reduction of benzaldehyde with phenylsilane. (A) Series of FTIR spectra (B) Integration of the carbonyl (blue) and hydride (red) absorption vs. time. Dotted line indicates the addition of the solution.

Scheme 2 -

 2 Scheme 2 -Leaching test and TEM of the supernatants (D) and (E), black bar is 50 nm

Scheme 3 -Scheme 4 -

 34 Scheme 3 -Formation of smaller Cu NPs in THF due to the addition of coordinating ligands. (A) Influence of the quantity of P(n-Bu)3 on Cu NPs. From left to right: no P(n-Bu)3; 1 equiv. per Cu atom; 8 equiv. per Cu atom; 250 equiv. per Cu atom; (B) Influence of two other ligands. Left: 1 equiv. of D BU per Cu atom; right: 1 equiv. of OAm per Cu atom. Scale bars are 50 nm. Red circles are a guide to the eye, indicating the newly-formed species.

  Reaction conditions: in a 10 mL closed tube, Cu NPs (0.6 mol%, 0.016 mmol of Cu) dispersed in THF (5 mL), P(n-Bu)3 (0.6 mol%, 0.016 mmol), PhCHO (5 mmol), hydride source (6 mmol). (a) 1 H NMR yield given for the conversion of benzaldehyde to the corresponding alcohol; n.d. = not detected (b) Complete after 20 min. (c) PMHS = polymethylhydrosiloxane. (d) benzaldehyde was fully converted into benzyl benzoate.

Table 1 -

 1 Reduction of benzaldehyde with various catalysts

	Entry	catalyst	Benzaldehyde conversion ( 1 H NMR)
	1	Cu NPs + P(n-Bu)3	yield) >99%
	2	none	NR
	3	Cu NPs	NR
	4	P(n-Bu)3	NR
	5	[Cu(acac)2]	NR
	6

Table 1

 1

, entry 6). The in situ formation of Cu NPs from CuI and PhSiH 3 has recently been reported by Sharma et al. in the C-N bond reaction formation of carbonyls with amines.

  Table2shows the results ordered by family and strength of hydrides. Benzaldehyde was fully reduced using Ph 2 SiH 2 or (EtO) 3 SiH (entries 2, 3) and only partially with TMDS (31%, entry 4).

	Hydrosilanes with a lower hydride donating ability proved to
	be unreactive in these conditions (entries 5-8). NaH acted as a
	catalyst for the disproportionation of benzaldehyde into
	benzyl benzoate, according to the Tishchenko reaction	56
	(entry 9), which occurs quicker than the direct reduction of
	benzaldehyde.
	Boron-based hydride donor such as NaBH 4 or 9-
	borabicyclo[3.3.1]nonane (9-BBN-H) were also highly reactive
	for the reduction of benzaldehyde (entries 10, 11).
	Interestingly, ammonium formate was not able to reduce
	benzaldehyde by hydrogenation (entry 12). 57-59

Table 2 -

 2 Reactivity of selected hydrides for the reduction of benzaldehyde and their effects on the Cu NPs.

	Entry	Hydride source	Conversion (a)
		Hydrosilanes, from stronger to softer	63
	1	PhSiH 3	>99%	(b)
	2	Ph 2 SiH 2		>99%
	3	(EtO) 3 SiH		>99%
	4	TMDS		31%
	5	PhMe 2 SiH		n.d.
	6	Et 3 SiH		n.d.
	7	Ph 3 SiH		n.d.
	8	PMHS (c)		n.d.
		Other hydride sources
	9	NaH	>99%	(d)
	10	NaBH 4		>99%
	11	(9-BBN-H) 2		>99%
	12	HCO 2 NH 4		n.d.
	13	H 2		n.d.

Acknowledgements

This work was performed in the framework of Idex ANR-10-IDEX-0001-02 PSL*. The "Cellule Energie" of CNRS provided financial support for IR instrumentation. Sorbonne Université, CNRS and Collège de France are acknowledged for financial support. The synchrotron SOLEIL is acknowledged for beamtime allocation on beamline SMIS (under proposal 20160209 and 20170383) and for the use of chemistry laboratory facilities onsite. We are very thankful to Christophe Sandt and Paul Dumas for helpful discussions about ATR measurements. Denis Lesage (Sorbonne University), Domitille Giaume and Claudine Keil (IRCP, Chimie Paris) are acknowledged for their expertise in ESI-MS, ICP-MS and GC-MS, respectively.

Notes and references

1 M. B. Gawande, A. Goswami, F.-X. Felpin, T. Asefa, X. Huang, R. Silva, X. Zou, R. Zboril and R. S. Varma, Chem. Rev., 2016, 116, 3722-3811.

Conflicts of interest

There are no conflicts to declare.