Solid-state 2H NMR Research Articles

Encasing Triaryltriazine with a Bulky Chiral Cap: Luminescent Chiral Crystalline Molecular Rotors with Modulation of Solid-State Chiroptical Properties Mediated by Molecular Rotation.

A novel structural motif for luminescent chiral crystalline molecular rotors with chiroptical properties correlated with the rotational motion in crystalline media is presented. This scaffold incorporates bulky chiral caps consisting of a homochiral binaphthyl moiety with a triisopropylsilyl (TIPS) group into triaryltriazine, as confirmed by single-crystal X-ray diffraction (XRD) analysis. Variable-temperature solid-state 2H NMR studies revealed a 4-fold rotation of the phenylenes occurred in the rotor crystal between 263 and 333 K, while a steric rotor analogue shows no rotational motion. Notably, a reduction in the dihedral angle of the binaphthyl moiety upon heating was observed in the chiral rotors, and a corresponding alteration of the circular dichroism (CD) signal was detected in the solid-state, while those of the steric rotors showed no alteration by the temperature change. We propose that the fast rotation of the phenyl rings affects the motion of neighboring isopropyl groups, leading to steric repulsion with the binaphthyl moieties and thereby inducing its conformational change. Furthermore, the chiral rotors exhibited circularly polarized phosphorescence in the solid-state at low temperature, originating from rotational displacement of the phenylene on triphenyltriazine during structural relaxation in the excited state. Meanwhile, the steric rotors showed significant circularly polarized fluorescence induced by the suppressed molecular motion via a sterically hindered lattice environment in the excited state. These results indicate that the bulky chiral cap introduced into the triaryltriazines, acting as a luminescent chiral crystalline molecular rotor, can be a useful scaffold for the modulation of solid-state chiroptical properties via molecular rotational motions.

Lipid Compositions of Liquid-Ordered and Liquid-Disordered Phases in Ternary Membranes of Sphingomyelin, Cholesterol, and Dioleoylphosphatidylcholine Determined by 2H NMR: Stearoyl-Sphingomyelin Compared with Its Palmitoyl Counterpart.

Sphingomyelin (SM) and cholesterol are the major lipids in the signaling platforms of cell membranes, known as lipid rafts. In particular, SM with a stearoyl chain (C18-SM) is abundant in specific tissues such as the brain, the most cholesterol-rich organ, whereas the distribution of palmitoyl (C16)-SM is ubiquitous. Here, we reveal the differences between palmitoyl- and stearoyl-SM in lipid-lipid interactions based on the tie lines obtained from the 2H solid-state NMR spectra of bilayer systems composed of SM/dioleoylphosphatidylcholine/cholesterol 33:33:33 and 40:40:20. Lipid probes carrying position-selective deuterations, 10',10'-d2-SM, 24-d1-cholesterol, and 6″,6″-d2-dioleoyl-phosphatidylcholine, were incorporated into the membranes. 2H NMR peaks from these probes in the membranes directly provide the lipid compositions of the liquid-ordered (Lo) and liquid-disordered (Ld) regions. Without using bulky fluorescent groups, these probes allow us to obtain the end points of the tie lines in a ternary phase diagram based on the lever rule. Consequently, the tie lines of the stearoyl-SM membranes were steeper than those of the palmitoyl-SM membranes, indicating that cholesterol content was higher in the Lo domains of stearoyl-SM, regardless of the total concentration of unsaturated phospholipids. When comparing the content of unsaturated lipids in the Lo domain, the stearoyl-SM membranes had a higher content than palmitoyl-SM membranes. These results revealed that stearoyl-SM is suitable for stabilizing biologically functional microdomains in cholesterol-rich organs, whereas palmitoyl-SM may be better suited for stabilizing domains in tissue membranes with normal cholesterol content. The small but significant differences in the lipid interactions between stearoyl-SM and palmitoyl-SM may be related to the spatiotemporal formation of functional domains in biological environments.

On the flexibility of 1,4-bis(phenylethynyl)benzene butyl ester organic crystal featuring mobile components

The quest for organic materials with compliant mechanical properties has significantly increased in the past few years in materials science and engineering. Crystalline organic compounds are excellent candidates for exploring and developing those long-lasting properties in the solid state since their fine structural functionalization may provide them with unique flexible behaviors. This study describes the 1,4-bis(phenylethynyl)benzene butyl ester synthesized in four steps and whose crystal can display elastic and elasto-plastic responses upon action with an external stimulus. A detailed characterization by single crystal X-ray diffraction revealed a layered crystal array that results from π-π stacking interactions, C–H⋯O and C-H⋯π bonds. Complementarily, variable temperature solid-state 13C and 2H NMR studies were carried out to probe the motion of the different components of the molecule and explore their possible association with the mechanical features. The compiled evidence indicates that the central phenylenes and the butyl groups experience molecular motion at different timescales, which, combined with the crystal array, facilitate the observed elastic and elasto-plastic flexibility. The results presented here not only contribute to advancing our understanding of flexible behavior but also could inspire potential applications such as flexible electronics.

Fumasep FAA-3-PK-130: Exploiting multinuclear solid-state NMR to shed light on undisclosed structural properties

Fumasep FAA-3-PK-130 is considered the state-of-the-art among the different commercially available Anion Exchange Membranes (AEMs). It is produced by Fumatech GmbH as a cost-effective blend of polyetheretherketone (PEEK) and poly (phenylene oxide) (PPO) characterized by high hydroxyl ions conductivity, high thermal and chemical resistance, and high dimensional stability. Nevertheless, the chemical structure of the anion exchange sites and their contents were unknown so far.In this paper, we report a detailed structural characterization of Fumasep FAA-3-PK-130 to identify the material phase composition, the nature of the conducting moieties and their interactions with the adsorbed water molecules. A complete phase segregation between PPO and PEEK was found on a micrometric scale from 1H spin-lattice relaxation times and micro-ATR analysis. Multinuclear (1H, 13C, 19F) Solid-State NMR spectra, combined with nuclear spin relaxation measurements, allowed us to identify the anion exchange moiety with benzyl-ethyl-dimethylammonium. This is present as functionalizing group of PPO monomers with a functionalization degree of about 40 %. Moreover, the mobility of water absorbed in the membrane was studied by 2H Solid-State NMR on samples hydrated with deuterated water under controlled relative humidity: at low relative moisture, two different types of environments were found for water molecules, compatible with two types of water-ion clusters, one of which contains water molecules with a restricted mobility, limited to C2 jumps, due to strong interactions with ions.

On the Structure and Role of Avian Eggshells: A 31P, 1H, and 13C Solid-State NMR Study.

The eggshell is a composite and highly ordered structure formed by biomineralization. Besides other functions, it has a vital and intricate role in the protection of an embryo from various potentially harsh environmental conditions. Solid-state nuclear magnetic resonance (SSNMR) has been used for detailed structural investigations of the chicken, tinamou, and flamingo eggshell materials. 31P NMR spectra reveal that hydroxyapatite and β-tricalcium phosphate in the ratio 3:2 represent major constituents of phosphate species in the eggshells. All three eggshells exhibit similar spectra, except for the line widths, which implies different structural order of phosphate species in the chicken, tinamou, and flamingo eggshells. 1H NMR spectra for these materials are comparable, differentiating overlapped peaks in three spectral regions at around 7, 4-5, and 1-2 ppm. These spectral regions have been attributed to protons from NH or CaHCO3, water, and possibly isolated monomeric water molecules or hydroxyl groups in calcium-deficient hydroxyapatite. 1H-13C CP MAS NMR revealed the presence of organic matter in the form of lipids and proteins. Two overlapped resonances in the carbonyl region at around 173 and 169 ppm are assigned to the carbonyls of the peptide bonds and the bicarbonate unit in calcite, respectively. Fourier-transform infrared spectroscopy (FTIR) spectra confirmed the presence of structural units detected in the NMR spectra.

Solid-state dynamics of binuclear N-heterocyclic carbene Au(I) rotor with para-phenylene rotator

Abstract Molecular dynamics in the crystalline solid state, typically constrained by a densely packed crystal environment, may offer opportunities to control the physical properties of solid-state materials. In this work, a neutral crystalline molecular rotor featuring a para-phenylene rotator encapsulated by N-heterocyclic carbene ligands and connected via a C–Au–C rotational axis is presented. Single-crystal X-ray diffraction studies, along with variable temperature solid-state 2H NMR spin-echo measurements, confirm the presence of 180° 2-fold rotational dynamics of the para-phenylene moiety in the solid state.

Unravelling Guest Dynamics in Crystalline Molecular Organics Using 2H Solid-State NMR and Molecular Dynamics Simulation.

2H solid-state NMR and atomistic molecular dynamics (MD) simulations are used to understand the disorder of guest solvent molecules in two cocrystal solvates of the pharmaceutical furosemide. Traditional approaches to interpreting the NMR data fail to provide a coherent model of molecular behavior and indeed give misleading kinetic data. In contrast, the direct prediction of the NMR properties from MD simulation trajectories allows the NMR data to be correctly interpreted in terms of combined jump-type and libration-type motions. Time-independent component analysis of the MD trajectories provides additional insights, particularly for motions that are invisible to NMR. This allows a coherent picture of the dynamics of molecules restricted in molecular-sized cavities to be determined.

A combined solid-state 1H, 13C, 17O NMR and periodic DFT study of hyperfine coupling tensors in paramagnetic copper(II) compounds

We report solid-state 1H, 13C, and 17O NMR determination of hyperfine coupling tensors (A-tensors) in several paramagnetic Cu(II) (d9, S = 1/2) complexes: trans-Cu(DL-Ala)2·H217O, Cu([1–13C]acetate)2·H2O, Cu([2–13C]acetate)2·H2O, and Cu(acetate)2·H217O. Using these new experimental results and some A-tensor data available in the literature for trans-Cu(L-Ala)2 and K2CuCl4·2H2O, we were able to examine the accuracy of A-tensor computation from a periodic DFT method implemented in the BAND program. We evaluated A-tensors on 1H (I = 1/2), 13C (I = 1/2), 14N (I = 1), 17O (I = 5/2), 39K (I = 3/2), 35Cl (I = 3/2), and 63Cu (I = 3/2) nuclei over a range spanning more than 3 orders of magnitude. We found that the BAND code can reproduce reasonably well the experimental results for both A-tensors and nuclear quadrupole coupling tensors.

Assessment of Hydrophilicity/Hydrophobicity in Mesoporous Silica by Combining Adsorption, Liquid Intrusion, and Solid-State NMR Spectroscopy.

We have developed a comprehensive strategy for quantitatively assessing the hydrophilicity/hydrophobicity of nanoporous materials by combining advanced adsorption studies, novel liquid intrusion techniques, and solid-state NMR spectroscopy. For this, we have chosen a well-defined system of model materials, i.e., the highly ordered mesoporous silica molecular sieve SBA-15 in its pristine state and functionalized with different amounts of trimethylsilyl (TMS) groups, allowing one to accurately tailor the surface chemistry while maintaining the well-defined pore structure. For an absolute quantification of the trimethylsilyl group density, quantitative 1H solid-state NMR spectroscopy under magic angle spinning was employed. A full textural characterization of the materials was obtained by high-resolution argon 87 K adsorption, coupled with the application of dedicated methods based on nonlocal-density functional theory (NLDFT). Based on the known texture of the model materials, we developed a novel methodology allowing one to determine the effective contact angle of water adsorbed on the pore surfaces from complete wetting to nonwetting, constituting a powerful parameter for the characterization of the surface chemistry inside porous materials. The surface chemistry was found to vary from hydrophilic to hydrophobic as the TMS functionalization content was increased. For wetting and partially wetting surfaces, pore condensation of water is observed at pressures P smaller than the bulk saturation pressure p0 (i.e., at p/p0 < 1) and the effective contact angle of water on the pore walls could be derived from the water sorption isotherms. However, for nonwetting surfaces, pore condensation occurs at pressures above the saturation pressure (i.e., at p/p0 > 1). In this case, we investigated the pore filling of water (i.e., the vapor-liquid phase transition) by the application of a novel, liquid water intrusion/extrusion methodology, allowing one to derive the effective contact angle of water on the pore walls even in the case of nonwetting. Complementary molecular simulations provide density profiles of water on pristine and TMS-grafted silica surfaces (mimicking the tailored, functionalized experimental silica surfaces), which allow for a molecular view on the water adsorbate structure. Summarizing, we present a comprehensive and reliable methodology for quantitatively assessing the hydrophilicity/hydrophobicity of siliceous nanoporous materials, which has the potential to optimize applications in heterogeneous catalysis and separation (e.g., chromatography).

Structure and reactivity of surface vanadia sites in bi-layered supported VOx/AlOx/SiO2 catalysts via solid-state NMR, first-principles calculations, and catalytic studies

By combining multinuclear 1H, 29Si, 27Al and 51V solid-state NMR experimental measurements with reactivity and selectivity data, as well as first-principles calculations, for ternary bi-layered supported VOx/Al2O3/SiO2 catalysts, the structure of the dehydrated surface vanadia species was determined for each combination of supported VOx and AlOx active components. The specific structure of the surface vanadia sites in the ternary bi-layered supported VOx/Al2O3/SiO2 catalyst system have been investigated for the first time.The following vanadia sites are proposed based on the current findings:At low vanadia content, surface VO(OH)(OSi)2 sites form on the alumina-free surface of the SiO2 support in the bi-layered supported VOx/Al2O3/SiO2 catalyst system. In addition, two types of VO(OSi)3 surface species are likely present in this system. On small alumina clusters, weakly bonded surface VO(OH)(OAl)2 sites also form, along with the sites containing mixed Si/Al pods VO(OH)(OAl)(OSi). As the size of alumina clusters increases, strongly bonded VO(OAl)3 centers form, alongside the surface sites containing mixed pods VO(OAl)2(OSi) and VO(OAl)(OSi)2. The content of these sites increases with the loading of vanadia. Comparing supported VOx/SiO2, VOx/Al2O3, and bi-layered VOx/Al2O3/SiO2 catalyst systems revealed differences in catalytic activity due to the presence of new sites with different pods, with OH groups as well as the influence of Al-O-Si bonds on the electronic structure of surface vanadia sites on the alumina clusters. During the formation of dimethyl ether (DME), the turnover frequency (TOFDME) of the catalysts decreases with increasing domain size of the alumina clusters on SiO2. Addition of surface VOx sites, however, slightly decreases the TOFDME with the higher vanadia content weakening the activity of the alumina clusters. When surface VOx exists predominantly as V/Al1 and V/Al2, TOFredox depend on the vanadia content with lower vanadia content resulting in higher the TOFredox values. The 51V NMR spectra show that this decrease in redox TOF value correlates with the appearance of vanadia sites associated with silica pods. The activity of the catalysts was tested in methanol conversion reactions.

1H/17O Chemical Shift Waves in Carboxyl-Bridged Hydrogen Bond Networks in Organic Solids.

We report solid-state 1H and 17O NMR results for four 17O-labeled organic compounds each containing an extensive carboxyl-bridged hydrogen bond (CBHB) network in the crystal lattice: tetrabutylammonium hydrogen di-[17O2]salicylate (1), [17O4]quinolinic acid (2), [17O4]dinicotinic acid (3), and [17O2]Gly/[17O2]Gly·HCl cocrystal (4). The 1H isotropic chemical shifts found for protons involved in different CBHB networks are between 8.2 and 20.5 ppm, which reflect very different hydrogen-bonding environments. Similarly, the 17O isotropic chemical shifts found for the carboxylate oxygen atoms in CBHB networks, spanning a large range between 166 and 341 ppm, are also remarkably sensitive to the hydrogen-bonding environments. We introduced a simple graphical representation in which 1H and 17O chemical shifts are displayed along the H and O atomic chains that form the CBHB network. In such a depiction, because wavy patterns are often observed, we refer to these wavy patterns as 1H/17O chemical shift waves. Typical patterns of 1H/17O chemical shift waves in CBHB networks are discussed. The reported 1H and 17O NMR parameters for the CBHB network models examined in this study can serve as benchmarks to aid in spectral interpretation for CBHB networks in proteins.

Tensile yield behavior of isotactic polybutene-1

Relative to polyethylene or polypropylene, isotactic polybutene-1 (iPB-1) in form I is of high value for commercial applications due to its excellent mechanical properties; whereas, it tends to exhibit inconspicuous yield behavior closely related to poor energy consumption and thus weak toughness when subjected to uniaxial stretching. Regret, few studies had addressed how to control iPB-1 tensile yield behavior. As the tensile yield behavior of form I iPB-1 depended on the applied annealing temperature Ta and time ta as well as cyclic loading-unloading conditions, iPB-1 three-phase structure evolution was carefully characterized by wide-line solid-state 1H NMR. With Ta or ta increasing, the weakening tensile yield behavior of iPB-1 was accompanied by a decreasing rigid phase content which can be recognized by 1H NMR rather than DSC, revealing that a higher rigid phase content in iPB-1 favors a more significant typical tensile yield behavior. Furthermore, the weakening tensile yield behavior of iPB-1 due to annealing at a higher temperature can slowly recover back while further annealing at a lower temperature, implying the reversibility of destroyed rigid phase. Cyclic loading-unloading under a suitable fixed strain can promote formation of rigid phase in iPB-1, favoring appearance of the typical yield behavior. Therefore, the mutual contact possibility, dislocation and slip of iPB-1 rigid phase were proposed to be responsible for the tensile yield behavior. The results are of significance for understanding the structural origin of tensile yield behavior of iPB-1 and further tuning toughness of iPB-1 for its industrial applications.

Quantification of Residual Water in Pharmaceutical Frozen Solutions Via 1H Solid-State NMR

Freezing is essential for the stability of biological drug substances and products, particularly in frozen solution formulations and during the primary drying of lyophilized preparations. However, the unfrozen segment within the frozen matrix can alter solute concentration, ionic strength, and stabilizer crystallization, posing risks of increased biophysical instability and faster chemical degradation. While quantifying the unfrozen water content is important for designing stable biopharmaceuticals, there is a lack of analytical techniques for in situ quantitative measurements. In this study, we introduce a 1H magic angle spinning NMR technique to identify the freezing point (Tice) and quantify mobile water content in frozen biologics, applying this method to analyze the freezing of a commercial high-concentration drug product, Dupixent®. Our results demonstrate that water freezing is influenced by buffer salt properties and formulation composition, including the presence of sugar cryoprotectants and protein concentration. Additionally, the 1H chemical shift can probe pH in the unfrozen phase, potentially predicting the microenvironmental acidity in the frozen state. Our proposed methodology provides fresh insights into the analysis of freeze-concentrated solutions, enhancing our understanding of the stability of frozen and lyophilized biopharmaceuticals.

Surface immobilization mechanisms of cobalt ions on hydroxyapatite catalyst supports

Cobalt deposition in an excess of solution was used to design Co-modified hydroxyapatite materials with various Co loadings and controlled dispersion. It is rationalized how the properties of hydroxyapatite supports (more or less stoichiometric compositions, nanorod or platelet morphologies and crystalline (100) zig-zag termination or non-apatitic hydrated external layer), influence the immobilization processes of Co by operating either with slightly acidic (natural) or basic pH of the suspension media. Four cobalt immobilization mechanisms impacting the final dispersion of Co on hydroxyapatites were identified by combining structural (XRD, 1H and 31P solid-state NMR, UV-Vis, Raman and X-ray fluorescence spectroscopies), surface (XPS) characterizations of Co-modified hydroxyapatites after drying and thermal treatment at 500 °C, and monitoring of the pH and the composition of the supernatant solutions during the Co deposition step. On dried Co-modified crystalline stoichiometric hydroxyapatite nanorods, cobalt is highly dispersed through cationic exchange or strong electrostatic adsorption (SEA) at slightly acidic or basic pH, respectively. After thermal treatment at 500 °C, only cation exchange preserved atomic dispersion of Co(II) ions since Co3O4 nanoparticles were observed on samples for which Co deposition occurred via SEA. On defective hydroxyapatite platelets, cobalt deposited at acidic natural pH could diffuse in an external non-apatitic layer, whereas under basic pH media, this surface layer was hydrolysed, resulting in the formation of a cobalt-substituted hydroxyapatite layer in which only a limited fraction of the surface cobalt species could be probed by XPS.

Solid-state 2H NMR investigation of molecular motion in proton-conducting polyacrylic acid/imidazole composites

The molecular motion of imidazole (Im) in proton-conducting polyacrylic acid (PAA)/Im composite materials (PAA/xIm, where x represents the number of moles of Im per mole of the carboxyl group of PAA) was investigated using solid-state 2H NMR. For the 2H NMR analysis of polymers in which multiple constituents with different kinetic states coexist, we propose the simultaneous analysis of two 2H NMR spectra observed by the quadruple echo method using different echo intervals. The 2H NMR spectra were analyzed by superimposing simulated spectra with different jumping rates of 180° flip and isotropic rotation of Im. For PAA/0.5Im-d3, Im undergoes 180° flip below 343 K and isotropic rotation above 363 K. For PAA/1.0Im-d3, Im undergoes 180° flip below 323 K and isotropic rotation above 363 K. In the temperature range of 333–343 K, Im undergoing 180° flip and isotropic rotation coexist in PAA/1.0Im-d3. The distributions of the jumping rates of 180° flip and isotropic rotation of Im were obtained. The increase in the amount of Im enhances the jumping rate of the isotropic rotation of Im and the proton conductivity of PAA/xIm at high temperatures.

Synthesis and morphological control of Ca5(PO4)3Cl and Ca2PO4Cl via the phase transformation of amorphous calcium phosphate in molten chlorides

In the present work, the phase conversion of amorphous calcium phosphate (ACP) in different molten chlorides (LiCl, NaCl, KCl, CaCl2) was investigated in detail. The main synthesis parameters influencing the phase purity and morphological features of the products include the chemical composition of molten salts, the heat treatment temperature and the ACP-to-flux ratio. The selective synthesis of single-phase Ca5(PO4)3Cl or Ca2PO4Cl depends on the content of CaCl2 in the reaction medium. The morphology control of Ca5(PO4)3Cl powders was achieved by varying the KCl/CaCl2 ratio in the flux, resulting in the formation of the particles of different size and shape. The KCl-rich fluxes led to the formation of relatively small nearly spherical particles, whereas the CaCl2-rich fluxes promoted an anisotropic growth of the Ca5(PO4)3Cl crystals resulting in the formation of monodispersed hexagonally-shaped microrods. Whereas the anisotropic growth was observed at relatively low temperature (750 °C) the increase of the reaction temperature up to 1200 °C significantly reduced this effect leading to the formation of the particles with obviously low aspect ratio. The phase crystallinity and purity were analyzed using powder X-ray diffraction, FTIR spectroscopy as well as 31P, 35Cl and 1H solid-state NMR. The morphological features and chemical composition of the synthesized products were studied by SEM/EDX analysis.

Biodegradable Nanocomposites Based on Blends of Poly(Butylene Adipate-Co-Terephthalate) (PBAT) and Thermoplastic Starch Filled with Montmorillonite (MMT): Physico-Mechanical Properties.

Poly(butylene adipate-co-terephthalate) (PBAT) is widely used for production of biodegradable films due to its high elongation, excellent flexibility, and good processability properties. An effective way to develop more accessible PBAT-based bioplastics for wide application in packaging is blending of PBAT with thermoplastic starch (TPS) since PBAT is costly with prices approximately double or even triple the prices of traditional plastics like polyethylene. This study is focused on investigating the influence of TPS/PBAT blend ratio and montmorillonite (MMT) content on the physical and mechanical properties and molecular mobility of TPS-MMT/PBAT nanocomposites. Obtained TPS-MMT/PBAT nanocomposites through the melt blending process were characterized using tensile testing, dynamic mechanical thermal analysis (DMTA), and X-ray diffraction (XRD), as well as solid-state 1H and 13C NMR spectroscopy. Mechanical properties demonstrated that the addition of TPS to PBAT leads to a substantial decrease in the tensile strength as well as in the elongation at break, while Young's modulus is rising substantially, while the effect of the MMT addition is almost negligible on the tensile stress of the blends. DMTA results confirmed the formation of TPS domains in the PBAT matrix. With increasing TPS content, mobility of starch-rich regions of TPS domains slightly increases. However, molecular mobility in glycerol-rich regions of TPS domains in the blends was slightly restricted. Moreover, the data obtained from 13C CP/MAS NMR spectra indicated that the presence of TPS in the sample decreases the mobility of the PBAT chains, mainly those located at the TPS/PBAT interfaces.

Elimination of homogeneous broadening in 1H solid-state NMR.

1H solid-state NMR spectra are plagued by low resolution, necessitating the use of complex pulse sequences or specialized equipment. We introduce a new resolution enhancement method, inspired by super-resolution microscopy, that uses a 2D Hahn-echo experiment to constrain deconvolution. The result is an effective doubling of the MAS frequency.

A copper-containing analog of the biomineral whitlockite: dissolution-precipitation synthesis, structural and biological properties.

In the present work, copper whitlockite (Cu-WH, Ca18Cu2(HPO4)2(PO4)12) was successfully synthesized and comprehensively characterized, founding the base knowledge for its future studies in medicine, particularly for bone regeneration. This material is a copper-containing analog of the well-known biomineral magnesium whitlockite (Mg-WH, Ca18Mg2(HPO4)2(PO4)12). The synthesis of powders was performed by a dissolution-precipitation method in an aqueous medium under hydrothermal conditions. Phase conversion from brushite (CaHPO4·2H2O) to Cu-WH took place in an acidic medium in the presence of Cu2+ ions. Optimization of the synthesis conditions in terms of medium pH, temperature, time, Ca/Cu molar ratio and concentration of starting materials was performed. The crystal structure of the synthesized products was confirmed by XRD, FTIR and Raman spectroscopy, 1H and 31P solid-state NMR, and EPR. Morphological features and elemental distribution of the synthesized powders were studied by means of SEM/EDX analysis. The ion release in SBF solution was estimated using ICP-OES. Cytotoxicity experiments were performed with MC3T3-E1 cells. The study on thermal stability revealed that the synthesized material is thermally unstable and gradually decomposes upon annealing to Cu-substituted β-Ca3(PO4)2 and Ca2P2O7.

Temperature-induced mobility in octacalcium phosphate impacts crystal symmetry: water dynamics studied by NMR crystallography.

Octacalcium phosphate (OCP, Ca8(PO4)4(HPO4)2·5H2O) is a notable calcium phosphate due to its biocompatibility, making it a widely studied material for bone substitution. It is known to be a precursor of bone mineral, but its role in biomineralisation remains unclear. While the structure of OCP has been the subject of thorough investigations (including using Rietveld refinements of X-ray diffraction data, and NMR crystallography studies), important questions regarding the symmetry and H-bonding network in the material remain. In this study, it is shown that OCP undergoes a lowering of symmetry below 200 K, evidenced by 1H, 17O, 31P and 43Ca solid-state NMR experiments. Using ab initio molecular-dynamics (MD) simulations and gauge including projected augmented wave (GIPAW) DFT calculations of NMR parameters, the presence of rapid motions of the water molecules in the crystal cell at room temperature is proved. This information leads to an improved description of the OCP structure at both low and ambient temperatures, and helps explain long-standing issues of symmetry. Remaining challenges related to the understanding of the structure of OCP are then discussed.