NMR Crystallography Research Articles

A dual-functional chemosensor based on acylhydrazone derivative for rapid detection of Zn(II) and Mg(II): Spectral properties, recognition mechanism and application studies

In this work, an acylhydrazone derivative (QN62) was developed via the one-step condensation of 6-hydroxy-2-naphthoic hydrazide with quinoline-8-carboxaldehyde. The structure of the QN62 compound was characterized by 1H NMR, 13C NMR, HR-MS (ESI), and X-ray crystallography. As a dual-functional turn-on fluorescence chemosensor, QN62 exhibited rapid recognition for Zn2+ in DMSO-H2O (4:1, v/v) and Mg2+ in ethanol-H2O (9:1, v/v). The enhancement in fluorescence detection was associated with the coordination reaction between QN62 and the target ions, which promoted intramolecular charge transfer and prevented the CN isomerization process. Simultaneously, a rapid color change from colorless to yellowish-green or yellow under UV light (365 nm) was easily visible to the naked eye. Under optimal conditions, the limit of detection and limit of quantification were 32.3 nM and 97.8 nM for Zn2+ and 16.1 nM and 48.9 nM for Mg2+, respectively. The recognition mechanism was reasonably speculated based on analysis of the Job’s plot, HR-MS, 1H NMR, and density functional theoretical calculations. Utilizing silica-gel plates fabricated from the QN62 chemosensor, the visual and rapid identification of Zn2+ and Mg2+ was successfully achieved, which could provide a convenient approach for on-site detection in environmental fields. The QN62 chemosensor could also quantify trace amounts of Zn2+ and Mg2+ in water samples. Furthermore, the cell imaging experiments indicated that QN62 could effectively sense intracellular Zn2+ and Mg2+, providing potential applications in biological systems.

A new cinnamaldehyde-rhodamine based dual chemosensor for Cu2+ and Fe3+ and its applicability in live cell imaging

A new fluorescent sensor, RT4 has been synthesized by reacting trans-4-(diethylamino)cinnamaldehyde with rhodamine B hydrazide in a one-step reaction. The characterization of RT4 was done by using FT-IR, 1H NMR, 13C NMR, and single crystal X-ray crystallography. In aqueous acetonitrile (1:1, v/v pH 7.5), RT4 exhibited a highly selective and sensitive colorimetric response upon recognition of Cu2+ and fluorometric response with Fe3+ ions. The calculated limit of detections (LOD) of RT4 with Cu2+ and Fe3+ were 0.20 and 0.18 µM at λabs/em = 555 and 585 nm, respectively. Test strips for colorimetric detection of Cu2+ and Fe3+ as an on-site test kit were successfully prepared. Furthermore, the MTT assay indicated that RT4 possess low cytotoxicity in human colorectal carcinoma HCT 116 after 24 h. The fluorescence microscopy experiment suggested that RT4 could also serve as a biological fluorescence probe for the detection of Fe3+in HCT 116 cells.

Cover Feature: Resolving the Chemical Formula of Nesquehonite via NMR Crystallography, DFT Computation, and Complementary Neutron Diffraction (Chem. Eur. J. 5/2023)

Cover Feature: Resolving the Chemical Formula of Nesquehonite via NMR Crystallography, DFT Computation, and Complementary Neutron Diffraction (Chem. Eur. J. 5/2023)

Frontiers of molecular crystal structure prediction for pharmaceuticals and functional organic materials.

The reliability of organic molecular crystal structure prediction has improved tremendously in recent years. Crystal structure predictions for small, mostly rigid molecules are quickly becoming routine. Structure predictions for larger, highly flexible molecules are more challenging, but their crystal structures can also now be predicted with increasing rates of success. These advances are ushering in a new era where crystal structure prediction drives the experimental discovery of new solid forms. After briefly discussing the computational methods that enable successful crystal structure prediction, this perspective presents case studies from the literature that demonstrate how state-of-the-art crystal structure prediction can transform how scientists approach problems involving the organic solid state. Applications to pharmaceuticals, porous organic materials, photomechanical crystals, organic semi-conductors, and nuclear magnetic resonance crystallography are included. Finally, efforts to improve our understanding of which predicted crystal structures can actually be produced experimentally and other outstanding challenges are discussed.

Large-scale Purification of Type III Toxin-antitoxin Ribonucleoprotein Complex and its Components from Escherichia coli for Biophysical Studies.

Toxin-antitoxin (TA) systems are widespread bacterial immune systems that confer protection against various environmental stresses. TA systems have been classified into eight types (I-VIII) based on the nature and mechanism of action of the antitoxin. Type III TA systems consist of a noncoding RNA antitoxin and a protein toxin, forming a ribonucleoprotein (RNP) TA complex that plays crucial roles in phage defence in bacteria. Type III TA systems are present in the human gut microbiome and several pathogenic bacteria and, therefore, could be exploited for a novel antibacterial strategy. Due to the inherent toxicity of the toxin for E. coli, it is challenging to overexpress and purify free toxins from E. coli expression systems. Therefore, protein toxin is typically co-expressed and co-purified with antitoxin RNA as an RNP complex from E. coli for structural and biophysical studies. Here, we have optimized the co-expression and purification method for ToxIN type III TA complexes from E. coli that results in the purification of TA RNP complex and, often, free antitoxin RNA and free active toxin in quantities required for the biophysical and structural studies. This protocol can also be adapted to purify isotopically labelled (e.g., uniformly 15N- or 13C-labelled) free toxin proteins, free antitoxin RNAs, and TA RNPs, which can be studied using multidimensional nuclear magnetic resonance (NMR) spectroscopy methods. Key features Detailed protocol for the large-scale purification of ToxIN type III toxin-antitoxin complexes from E. coli. The optimized protocol results in obtaining milligrams of TA RNP complex, free toxin, and free antitoxin RNA. Commercially available plasmid vectors and chemicals are used to complete the protocol in five days after obtaining the required DNA clones. The purified TA complex, toxin protein, and antitoxin RNA are used for biophysical experiments such as NMR, ITC, and X-ray crystallography.

Structural characterization of protein-DNA complexes using small angle X-ray scattering (SAXS) with contrast variation.

Molecular and atomic level characterization of transcription factor (TF)-DNA complexes is critical for understanding DNA-binding specificity and potentially structural changes that may occur in protein and/or DNA upon complex formation. Often TFs are large, multidomain proteins or contain disordered regions that contribute to DNA recognition and/or binding affinity but are difficult to structurally characterize due to their high molecular weight and intrinsic flexibility. This results in challenges to obtaining high resolution structural information using Nuclear Magnetic Resonance (NMR) spectroscopy due to the relatively large size of the protein-DNA complexes of interest or macromolecular crystallography due to the difficulty in obtaining crystals of flexible proteins. Small angle X-ray scattering (SAXS) offers a complementary method to NMR and X-ray crystallography that allows for low-resolution structural characterization of protein, DNA, and protein-DNA complexes in solution over a greater size range and irrespective of interdomain flexibility and/or disordered regions. One important caveat to SAXS data interpretation, however, has been the inability to distinguish between scattering coming from the protein versus DNA component of the complex of interest. Here, we present a protocol using contrast variation via increasing sucrose concentrations to distinguish between protein and DNA using the model protein bovine serum albumin (BSA) and DNA and the LUX ARRYTHMO TF-DNA complex. Examination of the scattering curves of the components individually and in combination with contrast variation allows the differentiation of protein and DNA density in the derived models. This protocol is designed for use on high flux SAXS beamlines with temperature-controlled sample storage and sample exposure units.

One-bond 13C-13C spin-coupling constants in saccharides: a comparison of experimental and calculated values by density functional theory using solid-state 13C NMR and X-ray crystallography.

Methyl aldohexopyranosides were 13C-labeled at contiguous carbons, crystallized, and studied by single-crystal X-ray crystallography and solid-state 13C nuclear magnetic resonance (NMR) spectroscopy to examine the degree to which density functional theory (DFT) can calculate one-bond 13C-13C spin-coupling constants (1JCC) in saccharides with sufficient accuracy to permit their use in MA'AT analysis, a newly-reported hybrid DFT/NMR method that provides probability distributions of molecular torsion angles in solution (Zhang et al., J. Phys. Chem. B, 2017, 121, 3042-3058; Meredith et al., J. Chem. Inf. Model., 2022, 62, 3135-3141). Experimental 1JCC values in crystalline samples of the doubly 13C-labeled compounds were measured by solid-state 13C NMR and compared to those calculated from five different DFT models: (1) 1JCC values calculated from single structures identical to those observed in crystalline samples by X-ray crystallography (all atom refinement); (2) 1JCC values calculated from the single structures in (1) but after Hirshfeld atom refinement (HAR); (3) 1JCC values calculated from the single structures in (1) after DFT-optimization of hydrogen atoms only; and (4 and 5) 1JCC values calculated in rotamers of torsion angle θ2 (C1-C2-O2-O2H) or ω (C4-C5-C6-O6) from which either specific or generalized parameterized equations were obtained and used to calculate 1JCC values in the specific θ2 or ω rotamers observed in crystalline samples. Good qualitative agreement was observed between calculated 1JCC values and those measured by solid-state 13C NMR regardless of the DFT model, but in no cases were calculated 1JCC values quantitative, differing (over-estimated) on average by 4-5% from experimental values. These findings, and those reported recently from solution NMR studies (Tetrault et al., J. Phys. Chem. B 2022, 126, 9506-9515), indicate that improvements in DFT calculations are needed before calculated 1JCC values can be used directly as reliable constraints in MA'AT analyses of saccharides in solution.

Abstract 1425: Regulating hypoxia response with small molecules: NMR and X-ray crystallography reveal binding mechanisms of two ARNT-TACC3 disruptors

Abstract 1425: Regulating hypoxia response with small molecules: NMR and X-ray crystallography reveal binding mechanisms of two ARNT-TACC3 disruptors

A new heteropentacyclic system via coupling sterically crowded o-benzoquinone with o-phenylenediamines.

The reaction between 3,5-di(tert-butyl)-o-benzoquinone 1 and o-phenylenediamine performed under oxidative conditions that is highly sensitive to the reaction conditions (type of solvent, ratio of reactants, and duration of the reaction) gives rise to various derivatives of a new condensed 10H-quinoxalino[3,2,1-kl]phenoxazin-10-one heteropentacyclic system. The reaction of 1 with N-phenyl-o-phenylenediamine results in the formation of three phenazine-like compounds and, unexpectedly, a derivative of a new spiro[1,3]dioxole-2,2'-furanyl-1H-benzo[d]imidazole system. The molecular structures of the prepared compounds were authenticated by NMR, mass spectra and X-ray crystallography data.

Resolving the Chemical Formula of Nesquehonite via NMR Crystallography, DFT Computation, and Complementary Neutron Diffraction.

Nesquehonite is a magnesium carbonate mineral relevant to carbon sequestration envisioned for carbon capture and storage of CO2 . Its chemical formula remains controversial today, assigned as either a hydrated magnesium carbonate [MgCO3 ⋅ 3H2 O], or a hydroxy- hydrated- magnesium bicarbonate [Mg(HCO3 )OH ⋅ 2H2 O]. The resolution of this controversy is central to understanding this material's thermodynamic, phase, and chemical behavior. In an NMR crystallography study, using rotational-echo double-resonance 13 C{1 H} (REDOR), 13 C-1 H distances are determined with precision, and the combination of 13 C static NMR lineshapes and density functional theory (DFT) calculations are used to model different H atomic coordinates. [MgCO3 ⋅ 3H2 O] is found to be accurate, and evidence from neutron powder diffraction bolsters these assignments. Refined H positions can help understand how H-bonding stabilizes this structure against dehydration to MgCO3 . More broadly, these results illustrate the power of NMR crystallography as a technique for resolving questions where X-ray diffraction is inconclusive.

Recognition Mechanisms between a Nanobody and Disordered Epitopes of the Human Prion Protein: An Integrative Molecular Dynamics Study.

Immunotherapy using antibodies to target the aggregation of flexible proteins holds promise for therapeutic interventions in neurodegenerative diseases caused by protein misfolding. Prions or PrPSc, the causal agents of transmissible spongiform encephalopathies (TSE), represent a model target for immunotherapies as TSE are prototypical protein misfolding diseases. The X-ray crystal structure of the wild-type (WT) human prion protein (HuPrP) bound to a camelid antibody fragment, denoted as Nanobody 484 (Nb484), has been previously solved. Nb484 was found to inhibit prion aggregation in vitro through a unique mechanism of structural stabilization of two disordered epitopes, that is, the palindromic motif (residues 113-120) and the β2-α2 loop region (residues 164-185). The study of the structural basis for antibody recognition of flexible proteins requires appropriate sampling techniques for the identification of conformational states occurring in disordered epitopes. To elucidate the Nb484-HuPrP recognition mechanisms, here we applied molecular dynamics (MD) simulations complemented with available NMR and X-ray crystallography data collected on the WT HuPrP to describe the conformational spaces occurring on HuPrP prior to Nb484 binding. We observe the experimentally determined binding competent conformations within the ensembles of pre-existing conformational states in solution before binding. We also described the Nb484 recognition mechanisms in two HuPrP carrying a polymorphism (E219K) and a TSE-causing mutation (V210I). Our hybrid approaches allow the identification of dynamic conformational landscapes existing on HuPrP and highly characterized by molecular disorder to identify physiologically relevant and druggable transitions.

DFT analysis and in vitro studies of isoxazole derivatives as potent antioxidant and antibacterial agents synthesized via one-pot methodology

Isoxazole and its derivatives derived from natural resources are very few. However, they have several applications in pharmaceutical industries, including antimicrobial, antitumor, anticancer, antifungal, and antibacterial activities. As a result, this research aimed to design a novel one-pot green approach to synthesize new oxazole derivatives. The derivatives were further explored for their antibacterial and antioxidant activities together with their density functional theory (DFT) analysis. Characterization of newly synthesized moieties was done by IR, 1H NMR, 13C NMR, CHN analysis, & single-crystal X-ray Crystallography. Further, these compounds were examined for their antibacterial potential by using Gentamycin as a standard drug against S. aureus and E. coli bacterial strains. The derivatives 4a, 4c, 4d, 4f, 4j, and 4k possessed excellent antibacterial potential against former, while 4c and 5 showed the highest activity against the later one. The derivatives were also analyzed for their antioxidant activities by using free radical scavenging (ABTS. & DPPH assays), and total antioxidant capacity. Here also, 4a, 4d, 4e, 4k, 4l, 4m, and 5 exhibited the most promising results. Finally, the DFT analysis was achieved by using the B3LYP methodology with a 6–311 + G(d,p) basis set to study the electronic structure of molecules and analysis of chemical reactivity descriptors such as hardness (η), Mulliken electronegativity (χ), chemical potential (μ) and electrophilicity (ω). These properties were calculated from the levels of the predicted frontier molecular orbitals and their energy gap.

Structural Determination of the Hexacoordinated [Zn(L)2]2+ Complex Isomer Type Using Solution-State NMR, DFT Calculations and X-ray Crystallography

The isomerism of zinc complex [Zn(L)2]2+ with tridentate ligand L having acetamide and pyridine groups on each side of the central amino- nitrogen atom has been investigated by DFT calculations, liquid state NMR and single-crystal X-ray diffraction. DFT was used for obtaining the ensembles of low-energy conformers of L and [Zn(L)2]2+ and for the calculation of NMR parameters for all conformers. For all generated conformers of L and [Zn(L)2]2+, the Mean Absolute Error [MAE(conf)] was tested as a structural quality parameter and compared with MAE(Bolz) for Boltzmann weighted ensembles. The most populated conformers had MAE(conf) values below 0.1 and 1 ppm for 1H shifts and 13C shifts, respectively. For the [Zn(L)2]2+ complex, the mer- C2 symmetric isomer was the most stable, in accordance with the X-ray structure of [Zn(L)2]2[SiF6][BF4]2. The cancellation of the magnetic equivalence of some nuclei valid for free L, when coordinated to the Zn2+ cation, was theoretically explained by the correct averaging of NMR parameters in the calculation procedure.

Thioether and Ether Furofuran Lignans: Semisynthesis, Reaction Mechanism, and Inhibitory Effect against α-Glucosidase and Free Radicals

The transformation of sesame lignans is interesting because the derived products possess enhanced bioactivity and a wide range of potential applications. In this study, the semisynthesis of 28 furofuran lignans using samin (5) as the starting material is described. Our methodology involved the protonation of samin (5) to generate an oxocarbenium ion followed by the attack from two different nucleophiles, namely, thiols (RSH) and alcohols (ROH). The highly diastereoselective thioether and ether furofuran lignans were obtained, and their configurations were confirmed by 2D NMR and X-ray crystallography. The mechanism underlying the reaction was studied by monitoring 1H NMR and computational calculations, that is, the diastereomeric α- and β-products were equally formed through the SN1-like mechanism, while the β-product was gradually transformed via an SN2-like mechanism to the α-congener in the late step. Upon evaluation of the inhibitory effect of the synthesized lignans against α-glucosidases and free radicals, the lignans 7f and 7o of the phenolic hydroxyl group were the most potent inhibitors. Additionally, the mechanisms underlying the α-glucosidase inhibition of 7f and 7o were verified to be of a mixed manner and noncompetitive inhibition, respectively. The results indicated that both 7f and 7o possessed promising antidiabetic activity, while simultaneously inhibiting α-glucosidases and free radicals.

Influence of nitro group on solvatochromism, nonlinear optical properties of 3-morpholinobenzanthrone: Experimental and theoretical study

We report the synthesis of 3-morpholino-9-nitrobenzanthrone (NMB) dye. By using FT-IR, 1H NMR, and X-ray crystallography, we characterized the molecular structure of the synthesized dye. The structural features of the dye were compared to those of an identical dye without nitro substituents. The push pull kind of benzanthrone dye (NMB) was examined for solvent-dependent photophysical properties. NMB exhibits a large Stokes shift. The polarity plots indicate that hydrogen-bonding interactions are influential in most of the solvents. Detailed structural analysis as well as one-photon absorption and emission process was computationally investigated for both the molecules. NMB exhibits significant two photon absorption (TPA) activity at various electron transitions ranging from visible to NIR regions. Further, Nonlinear absorption coefficient was calculated for the dye samples from the open aperture Z-scan data. The nonlinear absorption coefficient values were obtained for the dye samples for input laser pulse energies ranging from 5 to 20 µJ. The results decipher that these dye samples are prospective contenders for the fabrication of optical limiter devices. Nitro substituents at the active site enhance charge transfer, thereby enhancing the NLO response.

Investigation of the Influence of Various Functional Groups on the Dynamics of Glucocorticoids.

The basic configuration of glucocorticoid consists of four-fused rings associated with one cyclohexadienone ring, two cyclohexane rings, and one cyclopentane ring. The ways the structure and dynamics of five glucocorticoids (prednisone, prednisolone, prednisolone acetate, methylprednisolone, and methylprednisolone acetate) are altered because of the substitution of various functional groups with these four-fused rings are studied thoroughly by applying sophisticated solid-state nuclear magnetic resonance (NMR) methodologies. The biological activities of these glucocorticoids are also changed because of the attachment of various functional groups with these four-fused rings. The substitution of the hydroxyl group (with the C11 atom of the cyclohexane ring) in place of the keto group enhances the potential of the glucocorticoid to cross the cellular membrane. As a result, the bioavailability of prednisolone (the hydroxyl group is attached with the C11 atom of the cyclohexane ring) is increased compared to prednisone (the keto group is attached with the C11 atom of cyclohexane rings). Another notable point is that the spin-lattice relaxation rate at crystallographically distinct carbon nuclei sites of prednisolone is increased compared to that of the prednisone, which implies that the motional degrees of freedom of glucocorticoid is increased because of the substitution of the hydroxyl group in place of the keto group of the cyclohexane ring. The attachment of the methyl group with the C6 atom of cyclohexane rings further reduces the spin-lattice relaxation time at crystallographically distinct carbon nuclei sites of glucocorticoid and its bioactivity is also increased. By comparing the spin-lattice relaxation time and the local correlation time at crystallographically different carbon nuclei sites of three steroids prednisone, prednisolone, and methylprednisolone, it is observed that both the spin-lattice relaxation time and the local correlation time gradually decrease at each crystallographically distinct carbon nuclei sites when we move from prednisone to prednisolone to methyl-prednisolone. On the other hand, if we compare the same for prednisolone, prednisolone acetate, and methylprednisolone acetate, then we also observe that both the spin-lattice relaxation time and the local-correlation time gradually decrease from prednisolone to prednisolone acetate to methylprednisolone acetate for all chemically different carbon nuclei. It is also noticeable that both the spin-lattice relaxation time and the local-correlation time gradually decrease from prednisone to prednisolone to prednisolone acetate to methylprednisolone to methylprednisolone acetate for most of the carbon nuclei sites. From in silico analysis, it is also revealed that the bioavailability and efficacy of the glucocorticoid increase from prednisone to prednisolone to prednisolone acetate to methylprednisolone to methylprednisolone acetate. Hence, it can be concluded that the biological activity and the motional degrees of freedom of the glucocorticoids are highly correlated. These types of studies provide a clear picture of the structure-activity relationship of the drug molecules, which will enlighten the path of developing highly potent glucocorticoids with minimum side effects. Another important aspect of these types of studies is to provide information about the electronics configuration and nuclear spin dynamics at crystallographically different carbon nuclei sites of five glucocorticoids, which will enrich the field of "NMR crystallography".

Reactivity of the TpRu(HN=CPh2)(PPh3)−Azido complex and Insertion of Methylene into the Tp B−H Bond

• We report [3+2] cycloaddition reactions of alkyne with the ruthenium azido complex. • The stable triazolato and tetrazolato products obtained in all cases were N (2)-bound. • We report that during protonation of ruthenium azido complex, methylene insertion accidentally took place, to yield unusual boron-methylated product. • Their structures are elucidated by IR, NMR and X-ray crystallography. Herein, we report on the reactivity of an Ru(II) azido complex allowing the facile synthesis of further interesting complexes. Starting from the parent chlorido complex (HN=CPh 2 )[Ru]−Cl { 1 , [Ru] = Tp(PPh 3 )Ru; Tp = HB(pz) 3 , pz = pyrazolyl)} the title complex (HN=CPh 2 )[Ru]−N 3 ( 2 ) was obtained upon reaction with NaN 3 . The N (2)-bound 4,5-bis-(methoxycarbonyl)-1,2,3-triazolato complex (HN=CPh 2 )[Ru]−{N 3 C 2 (CO 2 Me) 2 } ( 3 ) was obtained from reaction of 2 with dimethyl acetylene dicarboxylate (DMAD). Protonation of 3 with HCl afforded the N -coordinated triazolato complex {HN 3 C 2 (CO 2 Me) 2 }[Ru]−Cl ( 4 ). Reaction of CS 2 with 2 produced the thiocyanato complex (HN=CPh 2 )[Ru]−NCS ( 5 ). The Ru tetrazolato complex (HN=CPh 2 )[Ru]−N 4 C[C(CN)=C(CN) 2 ] ( 6 ) was prepared from 2 and tetracyanoethylene (TCNE). The reaction of 2 with HX gave the 17-electron Ru(III) complexes (Cl)[Ru]−X ( 7a , X = Cl ; 7b , X = Br) and the Ru(II) complexes containing the methyl tris(pyrazolyl)borate ligand Me Tp(PPh 3 )(HN=CPh 2 )Ru−X ( 8a , X = Cl ; 8b , X = Br), as a result of an unusual methylene insertion into the B−H bond of the Tp ligand with the CH 2 Cl 2 solvent as the assumed source for the methylene. The structures of 4, 5, 7a, 7b and 8b had been determined by X-ray diffraction analysis.

NMR Crystallographic Approach to Study the Variation of the Dynamics of Quinine and Its Quasienantiomer Quinidine

The structure and dynamics of quinine and its quasienantiomer quinidine were studied at the atomic resolution by measuring the chemical shift anisotropy (CSA) tensor and site-specific spin–lattice relaxation time. For quinine, there are three crystallographically independent molecules “a”, “b”, and “c” in an asymmetric unit since its 13C CP-MAS SSNMR spectrum features three distinct resonance peaks for certain carbon nuclei. The 13C assignments are fulfilled by DFT calculations. The experimental 13C isotropic chemical shifts well match the calculated values. These variations of isotropic chemical shift for three independent molecules are also observed by two-dimensional 13C–1H heteronuclear correlation spectroscopy (HETCOR) of quinine. The spin–lattice relaxation time, and the principal components of CSA parameters are also varied substantially for certain carbon nuclei of “a”, “b”, and “c” molecules. For quinidine, its 13C CP-MAS SSNMR spectrum is remarkably different from that of quinine despite, their almost identical solution NMR spectra. Furthermore, the remarkable change in the structure and dynamics of quasienantiomers are also observed including the steric effect of the substituent vinyl group, the variation of helical motifs, and the variation of the strength of the intermolecular hydrogen bonds. The variation of the structure and dynamics of quasienantiomers are thoroughly studied by solid-state NMR measurements. These types of studies will enrich the field of NMR crystallography.

A Machine Learning Model of Chemical Shifts for Chemically and Structurally Diverse Molecular Solids.

Nuclear magnetic resonance (NMR) chemical shifts are a direct probe of local atomic environments and can be used to determine the structure of solid materials. However, the substantial computational cost required to predict accurate chemical shifts is a key bottleneck for NMR crystallography. We recently introduced ShiftML, a machine-learning model of chemical shifts in molecular solids, trained on minimum-energy geometries of materials composed of C, H, N, O, and S that provides rapid chemical shift predictions with density functional theory (DFT) accuracy. Here, we extend the capabilities of ShiftML to predict chemical shifts for both finite temperature structures and more chemically diverse compounds, while retaining the same speed and accuracy. For a benchmark set of 13 molecular solids, we find a root-mean-squared error of 0.47 ppm with respect to experiment for 1H shift predictions (compared to 0.35 ppm for explicit DFT calculations), while reducing the computational cost by over four orders of magnitude.

NMR Crystallography as a Vital Tool in Assisting Crystal Structure Determination from Powder XRD Data

Powder X-ray diffraction (XRD) and solid-state NMR spectroscopy are complementary techniques for investigating the structural properties of solids, and there are considerable opportunities and advantages to applying these techniques synergistically together in determining the structural properties of crystalline solids. This article provides an overview of the potential to exploit structural information derived from solid-state NMR data to assist and enhance the process of crystal structure determination from powder XRD data, focusing in particular on the structure determination of organic molecular materials.