Search

Thiophene, a key building block for the construction of conjugated materials, has been scarcely studied in halogen bonding (XB)-driven self-assemblies. In the present study, two thiophene derivatives modified at position 3 were (co-)crystallized using complementary XB donor/acceptor functional groups. Single-crystal X-ray diffraction analysis confirmed the presence of halogen and chalcogen bonding acting, in most cases, concomitantly. While the majority of the structures are governed by the conventional N···I motif, additional S···N and S···S contacts encouraged the cohesion of the supramolecular architectures. Density functional theory calculations shed the light on interaction energy, their respective contributions of the motifs to these non-covalent bonds, and the overall stability of these assemblies. To gain further insight into the formation and evidence of XB interactions, solution and mechanochemical syntheses of polymorphic adducts were performed, followed by 13C solid-state NMR analysis. Further, 1H and 19F{1H} solution-state NMR spectroscopy studies were carried out to highlight these interactions in the solution phase. The strength and directionality of halogen bonding thus reaffirm its role as a structure-directing agent for designing functional materials. The evidence of N···S chalcogen bonds in thiophene derivatives also broadens up the horizon of supramolecular chemistry in S-heterocycles, while necessitating further investigation for rational application in materials science.

We present a new operando approach for following reactions taking place in mechanochemistry, relying on the analysis of the evolution of the sound during milling. We show that differences in sound can be directly correlated to (physico)chemical changes in the reactor, making this technique attractive and complementary to others for monitoring mechanochemical reactions.

While ball-milling is becoming one of the common tools used by synthetic chemists, an increasing number of studies highlight that it is possible to further expand the nature and number of products which can be synthesized, by heating the reaction media during mechanochemical reactions. Hence, developing set-ups enabling to combine heating and milling is an important target, which has been looked into in both academic and industrial laboratories. Here, we report a new approach for heating up reaction media during ball-milling reactions, using induction heating (referred to as i-BM). Our set-up is highly attractive not only because it enables a very fast heating of the milling medium (reaching ≈80 °C in just 15 s), and that it is directly adaptable to commercially-available milling equipment, but also because it enables heating either the walls of the milling jars or the beads themselves, depending on the choice of the materials which compose them. Importantly, the possibility to heat a milling medium “from the inside” (when using for example a PMMA jar and stainless steel beads) is a unique feature compared to previously proposed systems. Through extensive numerical simulations, we then show that it is possible to finely tune the properties of this heating system (e.g. heating rate and maximum temperature reached), by playing with the characteristics of the milling system and/or the induction heating conditions used. Lastly, examples of applications of i-BM are given, showing how it can be used to help elucidate reaction mechanisms in ball-milling, to synthesize new molecules, and to control the physical nature of milling media.

International audience; The reaction between P2-type honeycomb layered oxides Na2Ni2TeO6 and K2Ni2TeO6 enables the formation of NaKNi2TeO6. The compound is characterized by X-ray diffraction and 23Na solid-state nuclear magnetic resonance spectroscopy, and the structure is discussed through density functional theory calculations. In addition to the honeycomb Ni/Te cationic ordering, NaKNi2TeO6 exhibits a unique example of alternation of sodium and potassium layers instead of a random alkali-mixed occupancy. Stacking fault simulations underline the impact of the successive position of the Ni/Te honeycomb layers and validate the presence of multiple stacking sequences within the powder material, in proportions that evolve with the synthesis conditions. In a broader context, this work contributes to a better understanding of the alkali-mixed layered compounds.

17 O NMR spectroscopy is a powerful technique, which can provide unique information regarding the structure and reactivity of biomolecules. However, the low natural abundance of 17 O (0.04%) generally requires working with enriched samples, which are not easily accessible. Here, we present simple, fast and cost-efficient 17 O-enrichment strategies for amino acids and peptides, using mechanochemistry. First, five unprotected amino acids were enriched under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with enrichment levels up to ~ 40%, yields ~ 60-85%, and no loss of optical purity. Subsequently, 17 O-enriched Fmoc/ t Bu-protected amino acids were produced on a 1g/day scale with high enrichment levels. Lastly, a site-selective 17 O-labeling of carboxylic functions in peptide side-chains was achieved for RGD and GRGDS peptides, with ~ 28% enrichment level. For all molecules, 17 O ssNMR spectra were recorded at 14.1T in reasonable times, making this an important step forward for future NMR studies of biomolecules.

Bone mineral has a complex 3D architecture that is essential to its mechanical properties. It is a complex calcium phosphate phase related to hydroxyapatite that also contains significant quantities of cell respiration metabolites, in particular: carbonate, citrate and lactate. An as-yet unanswered question is what, if any, role do these metabolites collectively play in determining the 3D architecture of bone mineral? Here we synthesize apatitic materials by transformation from precursor mineral phases containing citrate, lactate or carbonate so that the synthesis environment mimics the densely-packed ionic environment within which bone mineral forms in vivo, and so that we can understand the mineral factors that may direct bone mineral 3D architecture. We show that incorporating citrate and lactate leads to complex mineral architectures reminiscent of those in bone mineral, including curvature of the mineral crystals. Our results suggest that metabolic acids may assist the moulding of bone mineral to restricted spaces available for mineral in in vivo bone. We find that the incorporation of lactate creates a softer material and inhibits the transformation towards apatitic structures, which may help to explain why foetal bone – necessarily soft – contains considerable quantities of lactate. High levels of plasma citrate have been previously found to correlate with high bone mineral density. Here we find that citrate incorporation leads to mineral crystal curvature modelling that in in vivo bone mineral suggesting its importance in mineral morphology. We conclude that metabolic anions may play an important role in controlling bone mineral physicochemical properties and 3D architecture.

Calcium oxalate minerals of the general formula CaC

Oxygen-17 and deuterium are two quadrupolar nuclei that are of interest for studying the structure and dynamics of materials by solid-state nuclear magnetic resonance (NMR). Here, 17 O and 2 H NMR analyses of crystalline ibuprofen and terephthalic acid are reported. First, improved 17 O-labelling protocols of these molecules are described using mechanochemistry. Then, dynamics occurring around the carboxylic groups of ibuprofen are studied considering variable temperature 17 O and 2 H NMR data, as well as computational modelling (including molecular dynamics simulations). More specifically, motions related to the concerted double proton jump and the 180° flip of the H-bonded (-COOH)2 unit in the crystal structure were looked into, and it was found that the merging of the C=O and C-OH 17 O resonances at high temperatures cannot be explained by the sole presence of one of these motions. Lastly, preliminary experiments were performed with a 2 H-17 O diplexer connected to the probe. Such configurations can allow, among others, 2 H and 17 O NMR spectra to be recorded at different temperatures without needing to tune or to change probe configurations. Overall, this work offers a few leads which could be of use in future studies of other materials using 17 O and 2 H NMR.

43 Ca nuclear magnetic resonance (NMR) spectroscopy has been extensively applied to the detailed study of octacalcium phosphate (OCP), Ca8 (HPO4 )2 (PO4 )4 .5H2 O, and hybrid derivatives involving intercalated metabolic acids (viz., citrate, succinate, formate, and adipate). Such phases are of importance in the development of a better understanding of bone structure. High-resolution 43 Ca magic angle spinning (MAS) experiments, including double-rotation (DOR) 43 Ca NMR, as well as 43 Ca{1 H} rotational echo DOR (REDOR) and 31 P{43 Ca} REAPDOR NMR spectra, were recorded on a 43 Ca-labeled OCP phase at very high magnetic field (20 T), and complemented by ab initio calculations of NMR parameters using the Gauge-Including Projector Augmented Wave-density functional theory (GIPAW-DFT) method. This enabled a partial assignment of the eight inequivalent Ca2+ sites of OCP. Natural-abundance 43 Ca MAS NMR spectra were then recorded for the hybrid organic-inorganic derivatives, revealing changes in the 43 Ca lineshape. In the case of the citrate derivative, these could be interpreted on the basis of computational models of the structure. Overall, this study highlights the advantages of combining high-resolution 43 Ca NMR experiments and computational modeling for studying complex hybrid biomaterials.

17O NMR spectroscopy is a powerful analytical technique, which enables to access unique information regarding the structure and reactivity of biomolecules, such as peptides and proteins. However, due to the exceedingly low natural abundance of 17O (0.04 %), it is necessary to work with 17O-enriched samples, which are not easily accessible because of the experimental constraints and high costs associated with the traditional enrichment procedures. Here, we present simple, fast and cost-efficient labeling strategies for 17O-enrichment of amino acids and peptides. First, using mechanochemical saponification, a variety of unprotected amino acids were enriched within 30 min of milling under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with high enrichment levels (up to ~ 40 %), and in medium to high yields (~ 60 - 85 %) without the loss of their optical purity (ee > 99%). The labeling efficiency of the mechanochemical protocol was then compared to a re-optimised enrichment strategy based on acid-catalysed oxygen exchange. Subsequently, 17O-enriched Fmoc/tBu-protected amino acids were produced on a 1 g/day scale with high enrichment levels (~ 40 %), and in high synthetic yields (~ 75 - 85 %), by scaling up the mechanochemical enrichment followed by a Fmoc-protection step. Lastly, a direct site-selective 17O-labeling of carboxylic functions in peptide side-chains was developed and applied to the RGD and GRGDS peptides, reaching up to 29% enrichment level. Producing highly enriched molecules enabled to record 17O solid-state NMR spectra at 14.1 T in reasonable analytical times. Overall, this work represents an important step forward in providing easy access to highly 17O-enriched peptides and proteins to be subsequently studied by high-resolution 17O NMR spectroscopy.

Calcium oxalate minerals of general formula CaC2O4.xH2O are widely present in nature and usually associated with pathological calcifications, constituting up to 70 – 80% of the mineral component of renal calculi. The monohydrate phase (CaC2O4.H2O, COM) is the most stable form, accounting for the majority of the hydrated calcium oxalates found. These mineral phases have been studied extensively via X-ray diffraction, IR spectroscopy and, to a lesser extent, using 1H, 13C and 43Ca solid-state NMR spectroscopy. However, several aspects of their structure and reactivity are still unclear, such as the evolution from low- to high-temperature COM structures (LT-COM and HT-COM, respectively), and the involvement of water molecules in this phase transition. Here, we report for the first time a 17O and 2H solid-state NMR investigation of the local structure and dynamics of water in the COM phase. A new procedure for the selective 17O- and 2H-isotopic enrichment of water molecules within the COM mineral is presented using mechanochemistry, which employs only microliter quantities of enriched water, and leads to exchange yields up to ~30%. 17O NMR allows both crystallographically inequivalent water molecules in the LT-COM structure to be resolved, while 2H NMR studies provide unambiguous evidence that these water molecules are undergoing different types of motions at high temperatures without exchanging with one another. Dynamics appear to be essential for water molecules in these structures, which have not been accounted for in previous structural studies on the HT-COM structure due to lack of available tools — highlighting the importance of such NMR investigations for studying the crystallographic structure of biologically relevant minerals like calcium oxalates.

α-Canaphite (CaNa2P2O7·4H2O) is a layered calcium disodium pyrophosphate tetrahydrate phase of significant geological and potential biological interest. This study overcomes the lack of a reliable protocol to synthesize pure α-canaphite by using a novel simple and reproducible approach of double decomposition in solution at room temperature. The pure α-canaphite is then characterized from the atomic to the macroscopic level using a multitool and multiscale advanced characterization strategy, providing for the first time full resolution of the α-canaphite monoclinic structure, including the hydrogen bonding network. Synchrotron X-ray diffraction and neutron diffraction are combined with multinuclear solid state NMR experimental data and computational modeling via DFT/GIPAW calculations. Among the main characteristics of the α-canaphite structure are some strong hydrogen bonds and one of the four water molecules showing a different coordination scheme. This peculiar water molecule could be the last to leave the collapsed structure on heating, leading eventually to anhydrous α-CaNa2P2O7 and could also be involved in the internal hydrolysis of pyrophosphate ions as it is the closest water molecule to the pyrophosphate ions. Relating such detailed structural data on α-canaphite to its physico-chemical properties is of major interest considering the possible roles of canaphite for biomedical applications. The vibrational spectra of α-canaphite (deuterated or not) are analyzed and Raman spectroscopy appears to be a promising tool for the identification/diagnosis of such microcrystals in vitro, in vivo or ex vivo.

The description of the formation, structure, and reactivity of coordination networks and metal-organic frameworks (MOFs) remains a real challenge in a number of cases. This is notably true for compounds composed of Zn

The description of the formation, structure and reactivity of coordination networks and MOFs remains a real challenge in a number of cases. This is notably true for compounds composed of Zn2+ ions and terephthalate ligands (benzene 1,4-dicarboxylate, BDC), because of the difficulties in isolating them as pure phases and/or because of the presence of structural defects. Here, using mechanochemistry in combination with operando Raman spectroscopy, the observation of the formation of various zinc-terephthalate compounds was rendered possible, allowing the distinction and isolation of three intermediates during the ball-milling synthesis of Zn3(OH)4(BDC). An “NMR crystallography” approach was then used, combining solid-state NMR (1H, 13C and 17O) and DFT calculations, in order to refine the poorly described crystallographic structures of these phases. Particularly noteworthy are the high-resolution 17O NMR analyses, which were made possible in a highly efficient and cost-effective way, thanks to the selective 17O-enrichment of either hydroxyl or terephthalate groups by ball-milling. This allowed the presence of defect sites to be identified for the first time in one of the phases, and the nature of the H-bonding network of the hydroxyls to be established in another. Lastly, the possibility of using deuterated precursors (e.g. D2O and d4-BDC) during ball-milling is also introduced, as a means for observing specific transformations during operando Raman spectroscopy studies, that would not have been possible with hydrogenated equivalents. Overall, the synthetic and spectroscopic approaches developed herein are expected to push forward the understanding of the structure and reactivity of other complex coordination networks and MOFs.

The reaction between P2-type honeycomb layered oxides Na

In recent years, there has been increasing interest in developing cost‐efficient, fast, and user‐friendly 17O enrichment protocols to help to understand the structure and reactivity of materials by using 17O NMR spectroscopy. Here, we show for the first time how ball milling (BM) can be used to selectively and efficiently enrich the surface of fumed silica, which is widely used at industrial scale. Short milling times (up to 15 min) allowed modulation of the enrichment level (up to ca. 5 %) without significantly changing the nature of the material. High‐precision 17O compositions were measured at different milling times by using large‐geometry secondary‐ion mass spectrometry (LG‐SIMS). High‐resolution 17O NMR analyses (including at 35.2 T) allowed clear identification of the signals from siloxane (Si−O−Si) and silanols (Si−OH), while DNP analyses, performed by using direct 17O polarization and indirect 17O{1H} CP excitation, agreed with selective labeling of the surface. Information on the distribution of Si−OH environments at the surface was obtained from 2D 1H−17O D‐HMQC correlations. Finally, the surface‐labeled silica was reacted with titania and using 17O DNP, their common interface was probed and Si−O−Ti bonds identified., A fast, user‐friendly17O enrichment approach by ball milling was developed to selectively enrich the surface of fumed silica. A variety of high‐resolution solid‐state 17O NMR experiments (ultra‐high magnetic field (35.2 T), 17O MQMAS, 2D 17O−1H D‐HMQC, 17O DNP), demonstrate that siloxane and different silanol bonds present at the surface, including H‐bonded and isolated silanols, can be labeled and characterized in detail.

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and superparamagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPION suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term

Two mechanochemical procedures for 17O/18O-isotope labeling of fatty acids are reported: a carboxylic acid activation/hydrolysis approach and a saponification approach. The latter route allowed first-time enrichment of important polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA). Overall, a total of 9 pure labeled products were isolated in high yields (≥80%) and with high enrichment levels (≥37% average labeling of C=O and C-OH carboxylic oxygen atoms), under mild conditions, and in short time (, Two mechanochemical procedures for 17O/18O-isotope labeling of fatty acids are reported: a carboxylic acid activation/hydrolysis approach and a saponification approach.

The spectroscopic study of pathological calcifications (including kidney stones) is extremely rich and helps to improve the understanding of the physical and chemical processes associated with their formation. While FTIR imaging and optical/electron microscopies are routine techniques in hospitals, there has been a dearth of solid state NMR studies introduced into this area of medical research, probably due to the scarcity of this analytical technique in hospital facilities. This work introduces effective multinuclear and multi-dimensional solid state NMR methodologies to study the complex chemical and structural properties characterising kidney stone composition. As a basis for comparison three hydrates (n = 1, 2 and 3) of calcium oxalate are examined along with nine representative kidney stones. The multinuclear MAS NMR approach adopted investigates the 1H, 13C, 31P and 43Ca nuclei, with the 1H and 13C MAS NMR data able to be readily deconvoluted into the constituent elements associated with the different oxalates and organics present. For the first time, the full interpretation of highly resolved 1H NMR spectra is presented for the three hydrates, based on structure and local dynamics. The corresponding 31P MAS NMR data indicates the presence of low-level inorganic phosphate species, however the complexity of these data make the precise identification of the phases difficult to assign. This work provides physicians, urologists and nephrologists with additional avenues of spectroscopic investigation to interrogate this complex medical dilemma that requires real multi technique approaches to generate effective outcomes.

In recent years, there has been increasing interest in developing cost-efficient, fast, and user-friendly 17O enrichment protocols to help understand the structure and reactivity of materials using 17O NMR. Here, we show for the first time how ball milling (BM) can be used to selectively and efficiently enrich the surface of fumed silica, which is widely used at the industrial scale. Short milling times (up to 15 min) allowed modulation of the enrichment level (up to ca. 5%) without significantly changing the nature of the material. High-precision 17O-compositions were measured at different milling times using LG-SIMS. High-resolution 17O NMR analyses (including at 35.2 T) allowed clear identification of the signals from siloxane (Si-O-Si) and silanols (Si-OH), while DNP analyses, performed using direct 17O polarization and indirect 17O{1H} CP excitation, agreed with selective labeling of the surface. Information on the distribution of Si-OH environments at the surface was obtained from 2D 1H-17O D-HMQC correlations. Finally, the surface-labeled silica was reacted with titania and using 17O DNP, their common interface was probed and Si-O-Ti bonds identified.

Oxygen‐17 and deuterium are two quadrupolar nuclei that are of interest for studying the structure and dynamics of materials by solid‐state nuclear magnetic resonance (NMR). Here, 17O and 2H NMR analyses of crystalline ibuprofen and terephthalic acid are reported. First, improved 17O‐labelling protocols of these molecules are described using mechanochemistry. Then, dynamics occurring around the carboxylic groups of ibuprofen are studied considering variable temperature 17O and 2H NMR data, as well as computational modelling (including molecular dynamics simulations). More specifically, motions related to the concerted double proton jump and the 180° flip of the H‐bonded (–COOH)2 unit in the crystal structure were looked into, and it was found that the merging of the C=O and C–OH 17O resonances at high temperatures cannot be explained by the sole presence of one of these motions. Lastly, preliminary experiments were performed with a 2H–17O diplexer connected to the probe. Such configurations can allow, among others, 2H and 17O NMR spectra to be recorded at different temperatures without needing to tune or to change probe configurations. Overall, this work offers a few leads which could be of use in future studies of other materials using 17O and 2H NMR., 17O and 2H nuclear magnetic resonance (NMR) analyses of crystalline ibuprofen and terephthalic acid are reported. First, improved 17O‐labelling protocols of these molecules are described using mechanochemistry. Then, dynamics occurring around the carboxylic groups of ibuprofen are studied considering variable temperature 17O and 2H NMR data, and computational modelling. Lastly, preliminary experiments were performed with a 2H–17O diplexer connected to the probe. Overall, this work offers leads for future studies of other materials using 17O and 2H NMR.

Two mechanochemical procedures for 17O/18O-isotope labeling of fatty acids are reported: a carboxylic acid activation/hydrolysis approach and a saponification approach. The latter route allowed first-time enrichment of important polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA). Overall, a total of 9 pure labeled products were isolated in high yields (≥80%) and with high enrichment levels (≥37% average labeling of C=O and C-OH carboxylic oxygen atoms), under mild conditions, and in short time (

International audience; There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and superparamagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPION suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPION nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPION nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

International audience; Fatty acids are ubiquitous in biological systems and widely used in materials science, including for the formulation of drugs and the surface-functionalization of nanoparticles. However, important questions regarding the structure and reactivity of these molecules are still to be elucidated, including their mode of binding to certain metal cations or materials surfaces. In this context, we have developed novel, efficient, user-friendly, and cost-effective synthetic protocols based on ball-milling, for the 17O and 18O isotopic labeling of two key fatty acids which are widely used in (nano)materials science, namely stearic and oleic acid. Labeled molecules were analyzed by 1H and 13C solution NMR, IR spectroscopy, and mass spectrometry (ESI-TOF and LC-MS), as well as 17O solid state NMR (for the 17O labeled species). In both cases, the labeling procedures were scaled-up to produce up to gram quantities of 17O- or 18O-enriched molecules in just half-a-day, with very good synthetic yields (all ≥84%) and enrichment levels (up to an average of 46% per carboxylic oxygen). The 17O-labeled oleic acid was then used for the synthesis of a metal soap (Zn-oleate) and the surface-functionalization of ZnO nanoparticles (NPs), which were characterized for the first time by high-resolution 17O NMR (at 14.1 and 35.2 T). This allowed very detailed insight into (i) the coordination mode of the oleate ligand in Zn-oleate to be achieved (including information on Zn···O distances) and (ii) the mode of attachment of oleic-acid at the surface of ZnO (including novel information on its photoreactivity upon UV-irradiation). Overall, this work demonstrates the high interest of these fatty acid-enrichment protocols for understanding the structure and reactivity of a variety of functional (nano)materials systems using high resolution analyses like 17O NMR.

While oxygen-17 NMR is increasingly being used for elucidating the structure and reactivity of complex molecular and materials systems, much effort is still required for it to become a routine analytical technique. One of the main difficulties for its development comes from the very low natural abundance of oxygen-17, which implies that isotopic labeling is generally needed prior to NMR analyses. However, 17O-enrichment protocols are often unattractive in terms of cost, safety, and/or practicality, even for compounds as simple as metal oxides. Here, we demonstrate how mechanochemistry can be used in a highly efficient way for the direct 17O-isotopic labeling of a variety of s-, p- and d-block oxides which are of major interest for the preparation of functional ceramics and glasses: Li2O, CaO, Al2O3, SiO2, TiO2, and ZrO2. For each oxide, the enrichment step was performed under ambient conditions in less than 1 hour and at low cost, which makes these synthetic approaches highly appealing in comparison to the existing literature. Using high-resolution 17O solid state NMR and Dynamic Nuclear Polarization, atomic-level insight into the enrichment process is achieved, especially for titania and alumina. Indeed, it was possible to demonstrate that enriched oxygen sites are present not only at the surface, but also within the oxide particles. Moreover, information on the actual reactions occurring during the milling step could be obtained by 17O NMR, both in terms of their kinetics and the nature of the reactive species. Finally, it was demonstrated how high resolution 17O NMR can be used for studying the reactivity at the interfaces between different oxide particles during ball-milling, especially in cases when X-ray diffraction techniques are uninformative. More generally, such investigations will be useful not only for producing 17O-enriched precursors efficiently, but also for understanding better mechanisms of mechanochemical processes themselves.; While oxygen-17 NMR is increasingly being used for elucidating the structure and reactivity of complex molecular and materials systems, much effort is still required for it to become a routine analytical technique. One of the main difficulties for its development comes from the very low natural abundance of oxygen-17, which implies that isotopic labeling is generally needed prior to NMR analyses. However, 17O-enrichment protocols are often unattractive in terms of cost, safety, and/or practicality, even for compounds as simple as metal oxides. Here, we demonstrate how mechanochemistry can be used in a highly efficient way for the direct 17O-isotopic labeling of a variety of s-, p- and d-block oxides which are of major interest for the preparation of functional ceramics and glasses: Li2O, CaO, Al2O3, SiO2, TiO2, and ZrO2. For each oxide, the enrichment step was performed under ambient conditions in less than 1 hour and at low cost, which makes these synthetic approaches highly appealing in comparison to the existing literature. Using high-resolution 17O solid state NMR and Dynamic Nuclear Polarization, atomic-level insight into the enrichment process is achieved, especially for titania and alumina. Indeed, it was possible to demonstrate that enriched oxygen sites are present not only at the surface, but also within the oxide particles. Moreover, information on the actual reactions occurring during the milling step could be obtained by 17O NMR, both in terms of their kinetics and the nature of the reactive species. Finally, it was demonstrated how high resolution 17O NMR can be used for studying the reactivity at the interfaces between different oxide particles during ball-milling, especially in cases when X-ray diffraction techniques are uninformative. More generally, such investigations will be useful not only for producing 17O-enriched precursors efficiently, but also for understanding better mechanisms of mechanochemical processes themselves.

International audience; Materials containing a calcium phosphate component have been the subject of much interest to NMR spectroscopists, especially in view of understanding the structure and properties of mineralized tissues like bone and teeth, and of developing synthetic biomaterials for bone regeneration. Here, we present a selection of recent developments in their structural characterization using advanced solid state NMR experiments, highlighting the level of insight which can now be accessed.

Janus bis(N-heterocyclic carbenes) composed of a porphyrin core with two N-heterocyclic carbene (NHC) heads fused to opposite pyrroles were used as bridging ligands for the preparation of metal complexes. We first focused our attention on the synthesis of gold(i) chloride complexes [(NHC)AuCl] and investigated the substitution of the chloride ligand by acetylides to obtain the corresponding [(NHC)AuC[triple bond, length as m-dash]CR] complexes. Polyacetylides were then used to obtain molecular multiporphyrinic systems with porphyrins fused to only one NHC ligand, while main-chain organometallic polymers (MCOPs) were obtained when using Janus porphyrin bis(NHCs). Interestingly, MCOPs incorporating zinc(ii) porphyrins proved to be efficient as heterogeneous photocatalysts for the generation of singlet oxygen upon visible light irradiation.

While 17O NMR is increasingly being used for elucidating the structure and reactivity of complex molecular and materials systems, much effort is still required for it to become a routine analytical technique. One of the main difficulties for its development comes from the very low natural abundance of 17O (0.04%), which implies that isotopic labeling is generally needed prior to NMR analyses. However, 17O-enrichment protocols are often unattractive in terms of cost, safety, and/or practicality, even for compounds as simple as metal oxides. Here, we demonstrate how mechanochemistry can be used in a highly efficient way for the direct 17O isotopic labeling of a variety of s-, p-, and d-block oxides, which are of major interest for the preparation of functional ceramics and glasses: Li2O, CaO, Al2O3, SiO2, TiO2, and ZrO2. For each oxide, the enrichment step was performed under ambient conditions in less than 1 h and at low cost, which makes these synthetic approaches highly appealing in comparison to the existing literature. Using high-resolution solid-state 17O NMR and dynamic nuclear polarization, atomic-level insight into the enrichment process is achieved, especially for titania and alumina. Indeed, it was possible to demonstrate that enriched oxygen sites are present not only at the surface but also within the oxide particles. Moreover, information on the actual reactions occurring during the milling step could be obtained by 17O NMR, in terms of both their kinetics and the nature of the reactive species. Finally, it was demonstrated how high-resolution 17O NMR can be used for studying the reactivity at the interfaces between different oxide particles during ball-milling, especially in cases when X-ray diffraction techniques are uninformative. More generally, such investigations will be useful not only for producing 17O-enriched precursors efficiently but also for understanding better mechanisms of mechanochemical processes themselves., The direct 17O enrichment of s-, p-, and d-block metal oxides is achieved with high efficiency using mechanochemistry. Atomic-level insight into the enrichment process is obtained using high-resolution solid-state 17O NMR and dynamic nuclear polarization analyses, which demonstrate that enriched oxygen sites are present both at the surface and within the oxide particles. Moreover, it is demonstrated how these labeling schemes allow the study of unique aspects of mechanochemical reactions between oxides by 17O NMR.

The development of amorphous phosphate-based materials is of major interest in the field of biomaterials science, and especially for bone substitution applications. In this context, we herein report the synthesis of gel-derived hydrated amorphous calcium/sodium ortho/pyrophosphate materials at ambient temperature and in water. For the first time, such materials have been obtained in a large range of tunable orthophosphate/pyrophosphate molar ratios. Multi-scale characterization was carried out thanks to various techniques, including advanced multinuclear solid state NMR. It allowed the quantification of each ionic/molecular species leading to a general formula for these materials: [(Ca2+y Na+z H+3+x-2y-z)(PO43−)1-x(P2O74−)x](H2O)u. Beyond this formula, the analyses suggest that these amorphous solids are formed by the aggregation of colloids and that surface water and sodium could play a role in the cohesion of the whole material. Although the full comprehension of mechanisms of formation and structure is still to be investigated in detail, the straightforward synthesis of these new amorphous materials opens up many perspectives in the field of materials for bone substitution and regeneration. Statement of significance The metastability of amorphous phosphate-based materials with various chain length often improves their (bio)chemical reactivity. However, the control of the ratio of the different phosphate entities has not been yet described especially for small ions (pyrophosphate/orthophosphate) and using soft chemistry, whereas it opens the way for the tuning of enzyme- and/or pH-driven degradation and biological properties. Our study focuses on elaboration of amorphous gel-derived hydrated calcium/sodium ortho/pyrophosphate solids at 70 °C with a large range of orthophosphate/pyrophosphate ratios. Multi-scale characterization was carried out using various techniques such as advanced multinuclear SSNMR (31P, 23Na, 1H, 43Ca). Analyses suggest that these solids are formed by colloids aggregation and that the location of mobile water and sodium could play a role in the material cohesion.

Gemcitabine hydrochloride is an FDA-approved chemotherapeutic drug used in the treatment of various cancers. Several drawbacks of gemcitabine including its short in vivo half-life of 8-17 min associated with a rapid excretion by the kidneys and its poor membrane permeability have inspired research on a nanodelivery approach. In this study, we report ethylene-based periodic mesoporous organosilica nanoparticles (PMOs) for photodynamic therapy and the autonomous delivery of gemcitabine in cancer cells. Porphyrins were used as photosensitizers and were localized in the walls of the PMOs while a high loading capacity of gemcitabine was observed in the porous structure. Depending on the nature of the photosensitizer, and its aggregation state, we were able to perform one or two-photon photodynamic therapy. Two-photon excited photodynamic therapy combined with gemcitabine delivery led to a synergy and a very efficient cancer cell killing.

Porphyrin nanorods were prepared by ion-association between free-base meso 5,10,15,20-tetrakis-(4-[Formula: see text]-methylpyridinium)porphyrin cations and tetraphenylborate anions. The nanorods have variable lengths (up to a few micrometers long) and diameters ([Formula: see text]50–500 nm). Their structure at the molecular level was elucidated by combining multinuclear solid state NMR spectroscopy, synchrotron X-ray powder diffraction and DFT calculations.

International audience; The synthesis, characterization, and biological evaluation of a series of compounds incorporating two or three benzoxaborole moieties is reported. Three different synthetic strategies were used to explore within this series as much chemical space as possible, all starting from the 6-aminobenzoxaborole reagent: amide coupling, imine bond formation, and squarate coupling. Eleven new compounds were isolated in pure form, and single crystals were obtained for two of them. These compounds were then evaluated as carbonic anhydrase inhibitors against the cytosolic hCA I and II and the transmembrane hCA IV, IX, and XII isoforms. While the benzoxaborole scaffold has been recently introduced as a new chemotype for carbonic anhydrase inhibition, these new multivalent derivatives exhibited superior inhibitory activity against the tumor-associated isoform hCA IX. In particular, compared to monovalent 6-aminobenzoxaborole (K-I = 813 nM) and 6-carboxybenzoxaborole (K-I = 400 nM), derivative 2h characterized by a glutamic acid structural core and two benzoxaborole moieties was found to be more potent (K-I = 64 nM) and more selective over human hCA II.

Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, although SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs onto polymer surfaces is still a major challenge. Herein, we propose an efficient strategy for the direct and uniform anchoring of SPIONs on the surface of functionalized-polylactide (PLA) nanofibers via a simple free ligand exchange procedure to design PLA@SPIONs core@shell nanocomposites. The resulting PLA@SPIONs hybrid biomaterials are characterized by electron microscopy (scanning electron microscopy and transmission electron microscopy) and energy-dispersive X-ray spectroscopy analysis to probe the morphology and detect elements present at the organic-inorganic interface, respectively. A monolayer of SPIONs with a complete and homogeneous coverage is observed on the surface of PLA nanofibers. Magnetization experiments show that magnetic properties of the nanoparticles are well preserved after their grafting on the PLA fibers and that the size of the nanoparticles does not change. The absence of cytotoxicity, combined with a high sensitivity of detection in magnetic resonance imaging both in vitro and in vivo, makes these hybrid nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

International audience; 87Sr, 127I and 119Sn wideline NMR spectroscopy was successfully applied to inorganic and hybrid materials: (i) Sr derivatives of medicinal interest (Sr-malonate, Sr-pyrophosphates, mixed Ca,Sr-fluoroapatites); (ii) apatitic structures acting as host matrices for iodine; and (iii) Sn-derived oxo-clusters which can be used as inorganic nanobuilding blocks. The BRAIN (BRoadband Adiabatic INversion) CP (Cross Polarization) approach (by Schurko et al.) was applied to a non integer quadrupolar nucleus (87Sr, I=9/2). The sequence was used in combination with WURST (Wideband Uniform-Rate Smooth-Truncation) QCPMG (Quadrupolar Carr-Purcell Meiboom-Gill) for optimal sensitivity. We showed that 127I WURST QCPMG experiments were sufficiently sensitive to allow rapid characterization of the incorporation of iodide (I−) anions in lead vanadate/phosphate apatites, and that 127I acted as a sensitive probe for the description of local disorder. 1H/19F → 119Sn BRAIN CP was successfully applied to the detailed characterization of tin oxo-clusters, using 1H and 19F as spin baths. We demonstrated that BRAIN CP can be effectively used as a tool of spectral editing leading to the estimation of spatial proximities between 119Sn and 1H/19F nuclei.

A new layered hybrid polythiophene-silica material was obtained directly by hydrolysis and polycondensation (sol-gel) of a silylated-thiophene bifunctional precursor, and its subsequent oxidative polymerization by FeCl3. This precursor was judiciously designed to guarantee its self-assembly and the formation of a lamellar polymer-silica structure, exploiting the cooperative effect between the hydrogen bonding interactions, originating from the ureido groups and the &pi, stacking interactions between the thiophene units. The lamellar structure of the polythiophene-silica composite was confirmed by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) analyses. The solid-state nuclear magnetic resonance (NMR), UV-Vis, and photoluminescence spectra unambiguously indicate the incorporation of polythiophene into the silica matrix. Our work demonstrates that using a polymerizable silylated-thiophene precursor is an efficient approach towards the formation of nanostructured conjugated polymer-based hybrid materials.

Natural abundance 43Ca solid state NMR experiments are reported for the first time at ultra-high magnetic field (35.2 T) on a series of Ca-(pyro)phosphate and Ca-oxalate materials, which are of biological relevance in relation to biomineralization processes and the formation of pathological calcifications. The significant gain in both sensitivity and resolution at 35.2 T leads to unprecedented insight into the structure of both crystalline and amorphous phases.

International audience