High-Resolution 17O Solid-State NMR as a Unique Probe for Investigating Oxalate Binding Modes in Materials: The Case Study of Calcium Oxalate Biominerals.

Oxalate ligands are found in many classes of materials, including energy storage materials and biominerals. Determining their local environments at the atomic scale is thus paramount to establishing the structure and properties of numerous phases. Here, we show that high-resolution 17O solid-state NMR is a valuable asset for investigating the structure of crystalline oxalate systems. First, an efficient 17O-enrichment procedure of oxalate ligands is demonstrated using mechanochemistry. Then, 17O-enriched oxalates were used for the synthesis of the biologically relevant calcium oxalate monohydrate (COM) phase, enabling the analysis of its structure and heat-induced phase transitions by high-resolution 17O NMR. Studies of the low-temperature COM form (LT-COM), using magnetic fields from 9.4 to 35.2 T, as well as 13C-17O MQ/D-RINEPT and 17O{1H} MQ/REDOR experiments, enabled the 8 inequivalent oxygen sites of the oxalates to be resolved, and tentatively assigned. The structural changes upon heat treatment of COM were also followed by high-resolution 17O NMR, providing new insight into the structures of the high-temperature form (HT-COM) and anhydrous calcium oxalate α-phase (α-COA), including the presence of structural disorder in the latter case. Overall, this work highlights the ease associated with 17O-enrichment of oxalate oxygens, and how it enables high-resolution solid-state NMR, for "NMR crystallography" investigations.

Cation Distribution and Anion Transport in the La3Ga5-xGe1+xO14+0.5x Langasite Structure.

Exploration of compositional disorder using conventional diffraction-based techniques is challenging for systems containing isoelectronic ions possessing similar coherent neutron scattering lengths. Here, we show that a multinuclear solid-state Nuclear Magnetic Resonance (NMR) approach provides compelling insight into the Ga3+/Ge4+ cation distribution and oxygen anion transport in a family of solid electrolytes with langasite structure and La3Ga5-xGe1+xO14+0.5x composition. Ultrahigh field 71Ga Magic Angle Spinning (MAS) NMR experiments acquired at 35.2 T offer striking resolution enhancement, thereby enabling clear detection of Ga sites in different coordination environments. Three-connected GaO4, four-connected GaO4 and GaO6 polyhedra are probed for the parent La3Ga5GeO14 structure, while one additional spectral feature corresponding to the key (Ga,Ge)2O8 structural unit which forms to accommodate the interstitial oxide ions is detected for the Ge4+-doped La3Ga3.5Ge2.5O14.75 phase. The complex spectral line shapes observed in the MAS NMR spectra are reproduced very accurately by the NMR parameters computed for a symmetry-adapted configurational ensemble that comprehensively models site disorder. This approach further reveals a Ga3+/Ge4+ distribution across all Ga/Ge sites that is controlled by a kinetically governed cation diffusion process. Variable temperature 17O MAS NMR experiments up to 700 °C importantly indicate that the presence of interstitial oxide ions triggers chemical exchange between all oxygen sites, thereby enabling atomic-scale understanding of the anion diffusion mechanism underpinning the transport properties of these materials.

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.

Characterization of the Pb Coordination Environment and Its Connectivity in Lead Silicate Glasses: Results from 2D 207Pb NMR Spectroscopy.

The Pb-O coordination environment in binary (PbO)x(SiO2)100-x glasses with 30 ≤ x ≤ 70 is probed by using two-dimensional 207Pb nuclear magnetic resonance (NMR) isotropic-anisotropic correlation spectroscopy. The isotropic 207Pb NMR spectra show little composition-dependent evolution of the Pb-O nearest-neighbor coordination environment. The systematic variation of the chemical shift tensor parameters offers a unique insight into their local site symmetry and suggests the presence of pyramidal PbO3 and PbO4 sites with sterically active electron lone pairs and with Pb-O bond lengths ranging between 0.23 and 0.25 nm. The PbO3/PbO4 ratio shows a small but monotonic increase from ∼70:30 to 80:20 as the PbO content increases from 30 to 70 mol %. When taken together, the isotropic and anisotropic 207Pb NMR spectra suggest that the majority of the PbOn (3 ≤ n ≤ 4) pyramids in these glasses are connected to the SiO4 tetrahedra via Pb-O-Si linkages. A significant fraction of Pb-O-Pb linkages, where the oxygen is linked only to Pb atoms, appears only in glasses with PbO ≥ 60 mol %. These oxygen atoms appear to be corner-shared between the PbOn pyramids in the structure, and no evidence for edge-sharing between these pyramids is observed in this composition range. We hypothesize that a substantial fraction of the constituent PbOn pyramids start to participate in edge-sharing only at higher PbO contents (>70 mol %), which diminishes the glass-forming ability of the network. This work illustrates the potential of isotropic-anisotropic correlation NMR spectroscopy in structural studies involving nuclides with large chemical shift ranges and anisotropy.

An unusual ionic cocrystal of ponatinib hydrochloride: characterization by single-crystal X-ray diffraction and ultra-high field NMR spectroscopy.

This study describes the discovery of a unique ionic cocrystal of the active pharmaceutical ingredient (API) ponatinib hydrochloride (pon·HCl), and characterization using single-crystal X-ray diffraction (SCXRD) and solid-state NMR (SSNMR) spectroscopy. Pon·HCl is a multicomponent crystal that features an unusual stoichiometry, with an asymmetric unit containing both monocations and dications of the ponatinib molecule, three water molecules, and three chloride ions. Structural features include (i) a charged imidazopyridazine moiety that forms a hydrogen bond between the ponatinib monocations and dications and (ii) a chloride ion that does not feature hydrogen bonds involving any organic moiety, instead being situated in a "square" arrangement with three water molecules. Multinuclear SSNMR, featuring high and ultra-high fields up to 35.2 T, provides the groundwork for structural interpretation of complex multicomponent crystals in the absence of diffraction data. A 13C CP/MAS spectrum confirms the presence of two crystallographically distinct ponatinib molecules, whereas 1D 1H and 2D 1H-1H DQ-SQ spectra identify and assign the unusually deshielded imidazopyridazine proton. 1D 35Cl spectra obtained at multiple fields confirm the presence of three distinct chloride ions, with density functional theory calculations providing key relationships between the SSNMR spectra and H⋯Cl- hydrogen bonding arrangements. A 2D 35Cl → 1H D-RINEPT spectrum confirms the spatial proximities between the chloride ions, water molecules, and amine moieties. This all suggests future application of multinuclear SSNMR at high and ultra-high fields to the study of complex API solid forms for which SCXRD data are unavailable, with potential application to heterogeneous mixtures or amorphous solid dispersions.

Local Structure in Disordered Melilite Revealed by Ultrahigh Field 71Ga and 139La Solid-State Nuclear Magnetic Resonance Spectroscopy.

Multinuclear Nuclear Magnetic Resonance (NMR) spectroscopy of quadrupolar nuclei at ultrahigh magnetic field provides compelling insight into the short-range structure in a family of fast oxide ion electrolytes with La1+xSr1-xGa3O7+0.5x melilite structure. The striking resolution enhancement in the solid-state 71Ga NMR spectra measured with the world's unique series connected hybrid magnet operating at 35.2 T distinctly resolves Ga sites in four- and five-fold coordination environments. Detection of five-coordinate Ga centers in the site-disordered La1.54Sr0.46Ga3O7.27 melilite is critical given that the GaO5 unit accommodates interstitial oxide ions and provides excellent transport properties. This work highlights the importance of ultrahigh magnetic fields for the detection of otherwise broad spectral features in systems containing quadrupolar nuclei and the potential of ensemble-based computational approaches for the interpretation of NMR data acquired for site-disordered materials.

Evidence for Mixed Mg Coordination Environments in Silicate Glasses: Results from 25Mg NMR Spectroscopy at 35.2 T.

The Mg-O coordination environment of silicate glasses of composition CaMgSi2O6, Na2MgSi3O8, and K2MgSi5O12 is probed using ultrahigh-field (35.2 T) 25Mg magic angle spinning nuclear magnetic resonance (MAS NMR) and triple-quantum MAS NMR spectroscopy. These spectra clearly reveal the coexistence of 4-fold- (MgIV) and 6-fold- (MgVI) coordinated Mg in all glasses. The MgIV/MgVI ratio implies an average Mg-O coordination number of ∼5 for CaMgSi2O6 glass, bringing NMR results for the first time in good agreement with those reported in previous studies based on diffraction and X-ray absorption spectroscopy, thus resolving a decade-long controversy regarding Mg coordination in alkaline-earth silicate glasses. The Mg-O coordination number decreases to ∼4.5 in the alkali-Mg silicate glasses, indicating that Mg competes effectively with the low field strength alkali cations for the nonbridging oxygen in the structure to attain tetrahedral coordination. This work illustrates the promise of ultrahigh-field NMR spectroscopy in structural studies involving nuclides with low gyromagnetic ratio.

Charge-clustering induced fast ion conduction in 2LiX-GaF3: A strategy for electrolyte design.

2LiX-GaF3 (X = Cl, Br, I) electrolytes offer favorable features for solid-state batteries: mechanical pliability and high conductivities. However, understanding the origin of fast ion transport in 2LiX-GaF3 has been challenging. The ionic conductivity order of 2LiCl-GaF3 (3.20 mS/cm) > 2LiBr-GaF3 (0.84 mS/cm) > 2LiI-GaF3 (0.03 mS/cm) contradicts binary LiCl (10-12 S/cm) < LiBr (10-10 S/cm) < LiI (10-7 S/cm). Using multinuclear 7Li, 71Ga, 19F solid-state nuclear magnetic resonance and density functional theory simulations, we found that Ga(F,X)n polyanions boost Li+-ion transport by weakening Li+-X- interactions via charge clustering. In 2LiBr-GaF3 and 2LiI-GaF3, Ga-X coordination is reduced with decreased F participation, compared to 2LiCl-GaF3. These insights will inform electrolyte design based on charge clustering, applicable to various ion conductors. This strategy could prove effective for producing highly conductive multivalent cation conductors such as Ca2+ and Mg2+, as charge clustering of carboxylates in proteins is found to decrease their binding to Ca2+ and Mg2+.

Non-covalent matere bonds in perrhenates probed via ultrahigh field rhenium-185/187 NMR and zero-field NQR spectroscopy.

Matere bonds (MaB) to rhenium in a set of organic perrhenates are probed via185/187Re solid-state NMR in applied magnetic fields of up to 35.2 T, and via185/187Re NQR. 185/187Re quadrupolar couplings distinguish between MaB samples and control samples, and their precise values are governed by shear strain of the ReO4- anions.

Multi-technique structural analysis of zinc carboxylates (soaps).

A series of medium- and long-chain zinc carboxylates (zinc octanoate, zinc nonanoate, zinc decanoate, zinc undecanoate, zinc dodecanoate, zinc pivalate, zinc stearate, zinc palmitate, zinc oleate, and zinc azelate) was analyzed by ultra-high-field 67Zn NMR spectroscopy up to 35.2 T, as well as 13C NMR and FTIR spectroscopy. We also report the single-crystal X-ray diffraction structures of zinc nonanoate, zinc decanoate, and zinc oleate-the first long-chain carboxylate single-crystals to be reported for zinc. The NMR and X-ray diffraction data suggest that the carboxylates exist in three distinct geometric groups, based on structural and spectroscopic parameters. The ssNMR results presented here present a future for dynamic nuclear polarization (DNP)-NMR-based minimally invasive methods for testing artwork for the presence of zinc carboxylates.

Overcoming challenges in 67Zn NMR: a new strategy of signal enhancement for MOF characterization.

67 Zn solid-state NMR suffers from low sensitivity, limiting its ability to probe the Zn2+ surroundings in MOFs. We report a breakthrough in overcoming challenges in 67Zn NMR. Combining new cryogenic MAS probe technology and performing NMR experiments at a high magnetic field results in remarkable signal enhancement, yielding enhanced information for MOF characterization.

Pushing the limit of MQMAS for low-γ quadrupolar nuclei in pharmaceutical hydrochlorides.

Solid-state NMR of quadrupolar nuclei such as 35Cl has become a useful tool to characterize polymorphism in pharmaceutical hydrochlorides. The two-dimensional multiple-quantum magic-angle spinning (MQMAS) experiment can achieve isotropic resolution, and separate quadrupolar line shapes for samples with multiple sites but the pulse sequence efficiency is often low, limiting applications due to the intrinsically low NMR signals and rf field from the low gyromagnetic ratios γ. The use of cosine low-power MQMAS pulse sequences and high magnetic fields is presented to push the limit of MQMAS for insensitive low-γ quadrupolar nuclei. The improved efficiency and fields up to 35.2 T enable the acquisition of MQMAS spectra for pharmaceutical samples with multiple 35Cl sites, large quadrupolar couplings and/or in diluted dosage forms.

Fabrication of Super-Sized Metal Inorganic-Organic Hybrid Glass with Supramolecular Network via Crystallization-Suppressing Approach.

Metal coordination compound (MCC) glasses [e.g., metal-organic framework (MOF) glass, coordination polymer glass, and metal inorganic-organic complex (MIOC) glass] are emerging members of the hybrid glass family. So far, a limited number of crystalline MCCs can be converted into glasses by melt-quenching. Here, we report a universal wet-chemistry method, by which the super-sized supramolecular MIOC glasses can be synthesized from non-meltable MOFs. Alcohol and acid were used as agents to inhibit crystallization. The MIOC glasses demonstrate unique features including high transparency, shaping capability, and anisotropic network. Directional photoluminescence with a large polarization ratio (≈47 %) was observed from samples doped with organic dyes. This crystallization-suppressing approach enables fabrication of super-sized MCC glasses, which cannot be achieved by conventional vitrification methods, and thus allows for exploring new MCC glasses possessing photonic functionalities.

Satellite-transition double cross-polarization HETCOR under fast MAS.

Double-cross polarization to the satellite-transitions (STs) of half-integer quadrupolar nuclei is demonstrated using proton-detected heteronuclear correlation (HETCOR) under fast magic-angle spinning (MAS). By placing the rf frequency away from the central-transition (CT) and selective to the STs, average Hamiltonian theory shows a scaled effective rf field with a phase equal to the complex ST spinning sideband being irradiated. Such an effective rf field can excite and spinlock STs but the phase spread usually leads to signal cancellation in one-step excitation or cross polarization experiments. The cancellation does not occur for two-step double cross-polarization (DCP) HETCOR experiments, therefore high efficiencies can be obtained. With careful magic-angle calibration, ST and double-quantum ST (DQST) HETCOR experiments are demonstrated with the 35Cl nuclei in histidine·HCl·H2O. These experiments provide additional information over the commonly observed CT spectra and near isotropic resolution in the case of DQST of spin S = 3/2 quadrupolar nuclei.

Characterization of peptide O⋯HN hydrogen bonds via1H-detected 15N/17O solid-state NMR spectroscopy.

High sensitivity and resolution solid-state NMR methods are reported, that straightforwardly select hydrogen-bonded 15N-17O pairs from amongst all other nitrogen and oxygen sites in peptides, to aid protein secondary and tertiary structure determination. Significantly improved sensitivity is obtained with indirect 1H detection under fast MAS and stronger relayed dipole couplings.

An analytical treatment of electron spectral saturation for dynamic nuclear polarization NMR of rotating solids.

Saturation of electron magnetization by microwave irradiation under magic-angle spinning (MAS) is studied theoretically. The saturation is essential for dynamic nuclear polarization (DNP) enhancement of nuclear magnetic resonance signals. For a spin with a large g-anisotropy and a long T1 relative to the rotor period, the sample rotation distributes saturation to the whole powder sample spectrum. Analytical expressions for the saturation and frequency profiles are obtained. For a pair of coupled electrons such as those in bis-nitroxides, which are commonly used for MAS DNP, an el-er model (where el and er stand for electrons on the left and the right, respectively, in their spectral positions) is introduced to simplify the analysis of a coupled two-spin system under MAS. For such a system, strong electron couplings exchange magnetization during dipolar/J rotor events when the two electron frequencies cross each other. The exchange is equivalent to a swap of the el and er electrons. This allows for the treatment of a coupled spin pair as two independent spins such that an analytical solution can be obtained for the steady-state magnetization and the difference between the two electrons. The theoretical study with its analytical result provides a simple physical picture of electron saturation under MAS and of how radical properties and experimental parameters affect cross-effect DNP. The effects of depolarization and the extension to more coupled electron spins are also discussed using this approach.

17O solid state NMR as a valuable tool for deciphering reaction mechanisms in mechanochemistry: the case study on the 17O-enrichment of hydrated Ca-pyrophosphate biominerals.

The possibility of enriching in 17O the water molecules within hydrated biominerals belonging to the Ca-pyrophosphate family was investigated, using liquid assisted grinding (LAG) in the presence of 17O-labelled water. Two phases with different hydration levels, namely triclinic calcium pyrophosphate dihydrate (Ca2P2O7·2H2O, denoted t-CPPD) and monoclinic calcium pyrophosphate tetrahydrate (Ca2P2O7·4H2O, denoted m-CPPT ß) were enriched in 17O using a "post-enrichment" strategy, in which the non-labelled precursors were ground under gentle milling conditions in the presence of stoichiometric quantities of 17O-enriched water (introduced here in very small volumes ∼10 µL). Using high-resolution 17O solid-state NMR (ssNMR) analyses at multiple magnetic fields, and dynamic nuclear polarisation (DNP)-enhanced 17O NMR, it was possible to show that the labelled water molecules are mainly located at the core of the crystal structures, but that they can enter the lattice in different ways, namely by dissolution/recrystallisation or by diffusion. Overall, this work sheds light on the importance of high-resolution 17O NMR to help decipher the different roles that water can play as a liquid-assisted grinding agent and as a reagent for 17O-isotopic enrichment.

An Atomistic Picture of Boron Oxide Catalysts for Oxidative Dehydrogenation Revealed by Ultrahigh Field 11B-17O Solid-State NMR Spectroscopy.

Boron oxide/hydroxide supported on oxidized activated carbon (B/OAC) was shown to be an inexpensive catalyst for the oxidative dehydrogenation (ODH) of propane that offers activity and selectivity comparable to boron nitride. Here, we obtain an atomistic picture of the boron oxide/hydroxide layer in B/OAC by using 35.2 T 11B and 17O solid-state NMR experiments. NMR spectra measured at 35.2 T resolve the boron and oxygen sites due to narrowing of the central-transition powder patterns. A 35.2 T 2D 11B{17O} dipolar heteronuclear correlation NMR spectrum revealed the structural connectivity between boron and oxygen atoms. The approach outlined here should be generally applicable to determine atomistic structures of heterogeneous catalysts containing quadrupolar nuclei.

Correction to "First Direct Insight into the Local Environment and Dynamics of Water Molecules in the Whewellite Mineral Phase: Mechanochemical Isotopic Enrichment and High-Resolution 17O and 2H NMR Analyses".

[This corrects the article DOI: 10.1021/acs.jpcc.2c02070.].

Improved resolution for spin-3/2 isotopes in solids via the indirect NMR detection of triple-quantum coherences using the T-HMQC sequence.

The indirect NMR detection of quadrupolar nuclei in solids under magic-angle spinning (MAS) is possible with the through-space HMQC (heteronuclear multiple-quantum coherence) scheme incorporating the TRAPDOR (transfer of population in double-resonance) dipolar recoupling. This sequence, called T-HMQC, exhibits limited t1-noise. In this contribution, with the help of numerical simulations of spin dynamics, we show that most of the time, the fastest coherence transfer in the T-HMQC scheme is achieved when TRAPDOR recoupling employs the highest radiofrequency (rf) field compatible with the probe specifications. We also demonstrate how the indirect detection of the triple-quantum (3Q) coherences of spin-3/2 quadrupolar nuclei in solids improves the spectral resolution for these isotopes. The sequence is then called T-HMQC3. We demonstrate the gain in resolution provided by this sequence for the indirect proton detection of 35Cl nuclei in l-histidine∙HCl and l-cysteine∙HCl, as well as that of 23Na isotope in NaH2PO4. These experiments indicate that the gain in resolution depends on the relative values of the chemical and quadrupolar-induced shifts (QIS) for the different spin-3/2 species. In the case of NaH2PO4, we show that the transfer efficiency of the T-HMQC3 sequence employing an rf-field of 80 kHz with a MAS frequency of 62.5 kHz reaches 75% of that of the t1-noise eliminated (TONE) dipolar-mediated HMQC (D-HMQC) scheme.