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Lithium salts continue to find pharmaceutical applications, particularly as psychiatric medications. As with any active pharmaceutical ingredient, structural polymorphism is an important concern for lithium-based medications that can influence solubility and other physicochemical properties. Here we report a 13C, 1H, and 7Li magic-angle spinning solid-state nuclear magnetic resonance (MAS SSNMR) study of two 1:1 polymorphic ionic cocrystals of lithium 4-methoxybenzoate and L-proline (L4MPRO(α) and L4MPRO(β)). One-dimensional 13C cross-polarization MAS and two-dimensional heteronuclear correlation NMR spectra hint at differential mobilities of the proline and benzoate moieties for the two polymorphs. Five key resonances differ in 13C chemical shift by more than 1 ppm between the two polymorphs, clearly distinguishing between them. Gauge-including projector-augmented-wave density functional theory calculations of 13C and 1H magnetic shielding constants correlate strongly with the experimental chemical shifts for both polymorphs. R2 and root-mean-square deviation metrics are shown to be insufficient in the case of 13C, but sufficient in the case of 1H, for differentiating between the polymorphs. 7Li satellite-transition MAS NMR of both polymorphs are identical, as are the computed lithium magnetic shielding constants, demonstrating the insensitivity of 7Li NMR to polymorphism in these samples. This work highlights the utility of solid-state NMR spectroscopy for examining ionic salt cocrystals and also highlights some caveats in this regard. [ABSTRACT FROM AUTHOR]

Double-rotation (DOR) solid-state NMR spectroscopy is a high-resolution technique developed in the late 1980s. Although multiple-quantum magic-angle spinning (MQMAS) became the most widely used high-resolution method for half-integer spin quadrupoles after 1995, development and application of DOR NMR to a variety of chemical and materials science problems has endured. This Trend article recapitulates the development of DOR NMR, discusses various applications, and describes possible future directions. The main technical limitations specific to DOR NMR are simply related to the size of the double rotor system. The relatively large outer rotor (and thus coil) used for most applications over the past 35 years translates into relatively low rotor spinning frequencies, a low filling factor, and weak radiofrequency powers available for excitation and for proton decoupling. Ongoing developments in NMR instrumentation, including ever-shrinking MAS rotors and spherical NMR rotors, could solve many of these problems and may augur a renaissance for DOR NMR. [Display omitted] • Advances in double-rotation solid-state NMR spectroscopy are reviewed. • DOR NMR provides high-resolution spectra of quadrupolar nuclei in one dimension. • Limitations include a poor filling factor, low spinning rates, and low rf powers. • New developments in magic angle spinning technology could reinvigorate DOR NMR. [ABSTRACT FROM AUTHOR]

Phenomena such as anticooperativity and competition among non‐covalent bond donors and acceptors are key considerations when exploring the polymorphic and stoichiomorphic landscapes of binary and higher‐order cocrystalline architectures. We describe the preparation of four cocrystals of 1,3,5‐trifluoro‐2,4,6‐triiodobenzene with N‐heterocyclic compounds, namely acridine, 3‐aminopyridine, 4‐methylaminopyridine, and 1,2‐di(4‐pyridyl)ethane. The cocrystals, which are characterized by single‐crystal and powder X‐ray diffraction experiments, all show moderately strong and directional iodine⋅⋅⋅nitrogen halogen bonds with reduced distance parameters ranging from 0.79 to 0.92 and carbon‐iodine⋅⋅⋅nitrogen bond angles ranging from 165.4(3) to 175.31(7)°. The cocrystal comprising 1,3,5‐trifluoro‐2,4,6‐triiodobenzene and acridine provides a relatively rare example where all three halogen bond donor sites form halogen bonds with three acceptor molecules, overcoming an anticooperative effect. This effect manifests itself through the lengthening of non‐halogen‐bonded C−I bonds, weakening their potential to form halogen bonds. The effect is only observed once two halogen bonds have been formed to 1,3,5‐trifluoro‐2,4,6‐triiodobenzene; one such bond does not appear to be adequate. Among the four cocrystals studied, competition between the pyridyl nitrogen atoms and the amine nitrogen atoms suggests that the former are the preferred halogen bond acceptors. Analysis by Hirshfeld fingerprint plots and 13C and 19F magic‐angle spinning solid‐state nuclear magnetic resonance (NMR) spectroscopy provides additional insights into the prevalence of various short contacts in the crystal structures and into the spectral response to halogen‐bond‐induced cocrystallization. [ABSTRACT FROM AUTHOR]

Chemically informative J couplings between pairs of quadrupolar nuclei in dimetallic and dimetalloid coordination motifs are measured using J-resolved solid-state NMR experiments. It is shown that the application of a double-quantum filter is necessary to observe the J splittings and that, under these conditions, only a simple doublet is expected. Interestingly, the splitting is amplified if the spins are magnetically equivalent, making it possible to measure highly precise J couplings and unambiguously probe the symmetry of the molecule. This is demonstrated experimentally by chemically breaking the symmetry about a pair of boron spins by reaction with an N-heterocyclic carbene to form a β-borylation reagent. The results show that the J coupling is a sensitive probe of bonding in diboron compounds and that the J values quantify the weakening of the B-B bond which occurs when forming an sp2-sp3 diboron compound, which is relevant to their reactivity. Due to the prevalence of quadrupolar nuclei among transition metals, this work also provides a new approach to probe metal-metal bonding; results for Mn2(CO)10 are provided as an example. [ABSTRACT FROM AUTHOR]

Three novel chalcogen‐bonded cocrystals featuring 3,4‐dicyano‐1,2,5‐selenodiazole (C4N4Se) or 3,4‐dicyano‐1,2,5‐tellurodiazole (C4N4Te) as chalcogen‐bond donors and hydroquinone (C6H6O2), tetraphenylphosphonium chloride (C24H20P+·Cl−) or tetraethylphosphonium chloride (C8H20P+·Cl−) as chalcogen‐bond acceptors have been prepared and characterized by single‐crystal X‐ray diffraction (XRD), powder X‐ray diffraction and 77Se/125Te magic‐angle spinning solid‐state NMR spectroscopy. The single‐crystal XRD results show that the chalcogenodiazole molecules interact with the electron donors through two σ‐holes on each of the chalcogen atoms, which results in highly directional and moderately strong chalcogen bonds. Powder XRD confirms that the crystalline phases are preserved upon moderate grinding of the samples for solid‐state NMR experiments. Measurement of 77Se and 125Te chemical shift tensors via magic‐angle spinning solid‐state NMR spectroscopy confirms the number of magnetically unique chalcogen sites in each asymmetric unit and reveals the impact of chalcogen‐bond formation on the local electronic structure. These NMR data are further assessed in the context of analogous data for a wider range of crystalline chalcogen‐bonded systems. [ABSTRACT FROM AUTHOR]

Abstract: Residual dipolar couplings between spin-1/2 and quadrupolar nuclei are often observed and exploited in the magic-angle spinning (MAS) NMR spectra of spin-1/2 nuclei. These orientation-dependent splittings contain information on the dipolar interaction, which can be translated into structural information. The same type of splittings may also be observed for pairs of quadrupolar nuclei, although information is often difficult to extract from the quadrupolar-broadened lineshapes. Here, the complete theory for describing the dipolar coupling between two quadrupolar nuclei in the frequency domain by Hamiltonian diagonalization is given. The theory is developed under MAS and double-rotation (DOR) conditions, and is valid for any spin quantum numbers, quadrupolar coupling constants, asymmetry parameters, and tensor orientations at both nuclei. All terms in the dipolar Hamiltonian become partially secular and contribute to the NMR spectrum. The theory is validated using experimental 11B and 35/37Cl NMR experiments carried out on powdered B-chlorocatecholborane, where both MAS and DOR are used to help separate effects of the quadrupolar interaction from those of the dipolar interaction. It is shown that the lineshapes are sensitive to the quadrupolar coupling constant of both nuclei and to the J coupling (including its sign). From these experiments, the dipolar coupling constant for a heteronuclear spin pair of quadrupolar nuclei may be obtained as well as the sign of the quadrupolar coupling constant of the perturbing nucleus; these are two parameters that are difficult to obtain experimentally otherwise. [Copyright &y& Elsevier]

The group 2 metal halides and corresponding metal halide hydrates serve as useful model systems for understanding the relationship between the electric field gradient (EFG) and chemical shift (CS) tensors at the halogen nuclei and the local molecular and electronic structure. Here, we present a 35/37Cl and 43Ca solid-state nuclear magnetic resonance (SSNMR) study of CaCl2. The 35Cl nuclear quadrupole coupling constant, 8.82(8) MHz, and the isotropic chlorine CS, 105(8) ppm (with respect to dilute NaCl(aq)), are different from the values reported previously for this compound, as well as those reported for CaCl2·2H2O. Chlorine-35 SSNMR spectra are also presented for CaCl2·6H2O, and when taken in concert, the SSNMR observations for CaCl2, CaCl2·2H2O, and CaCl2·6H2O clearly demonstrate the sensitivity of the chlorine EFG and CS tensors to the local symmetry and to changes in the hydration state. For example, the value of δiso decreases with increasing hydration. Gauge-including projector-augmented wave (GIPAW) density functional theory (DFT) calculations are used to substantiate the experimental SSNMR findings, to rule out the presence of other hydrates in our samples, to refine the hydrogen positions in CaCl2·2H2O, and to explore the isostructural relationship between CaCl2 and CaBr2. Finally, the 43Ca CS tensor span is measured to be 31(5) ppm for anhydrous CaCl2, which represents only the fifth CS tensor span measurement for calcium. [ABSTRACT FROM AUTHOR]

Zeroth-order regular approximation (ZORA) density functional theory (DFT) calculations of one-bond X-19F indirect nuclear spin-spin coupling ( J) tensors were performed on a series of fluorine-containing compounds covering several valence shell electron pair repulsion (VSEPR) theory geometries for which J, by symmetry, is not required to be axially symmetric. The calculations show that the antisymmetric components of J are only of the same order of magnitude as the principal components of the symmetric J-coupling tensor for a few geometries, and that in cases of approximate axial symmetry along the bond, J remains nearly axially symmetric with its unique component along the bond. In general, different species having the same nominal geometry tend to have similar tensor orientations, magnitudes of anisotropy of J relative to the isotropic coupling constant, as well as the same dominant contributions from the different coupling mechanisms. Structures are also systematically modified to determine how the tensor components depend on geometrical parameters. The isotropic coupling constants are subsequently interpreted using a natural localized molecular orbital (NLMO) approach. Our results could prove to be useful for future experimental characterizations of J tensors in systems having symmetry properties that do not force J to be axially symmetric or coincident with the dipolar coupling tensor. [ABSTRACT FROM AUTHOR]

Calcium is an important component of materials, metalloproteins, minerals, glasses, and small inorganic and organic complexes. However, NMR spectroscopy of the quadrupolar 43Ca nuclide remains difficult primarily due to its low natural abundance and low resonance frequency. In this Perspective, experimental challenges and recent successes in the field are highlighted, with a focus on solid-state 43Ca NMR spectroscopy. Solution 43Ca NMR studies of calcium-binding biomolecules are also presented. The structural insights afforded from quadrupolar and chemical shift parameters are examined. For example: isotropic chemical shifts have been shown to correlate with the mean Ca–O distance and also with calcium coordination number; quadrupolar coupling constants and chemical shift tensor spans have been shown to be useful probes of polymorphism; and, distance measurements involving 43Ca have been recently demonstrated. Lastly, challenges and opportunities for the future are considered. [ABSTRACT FROM AUTHOR]

XH/π interactions make important contributions to biomolecular structure and function. These weakly polar interactions, involving π-system acceptor groups, are usually identified from the three-dimensional structures of proteins. Here, nuclear magnetic resonance spectroscopy has been used to directly detect methyl/π (Me/π) interactions in proteins at atomic resolution. Density functional theory calculations predict the existence of weak scalar (J) couplings between nuclei involved in Me/π interactions. Using an optimized isotope-labelling strategy, these J couplings have been detected in proteins using nuclear magnetic resonance spectroscopy. The resulting spectra provide direct experimental evidence of Me/π interactions in proteins and allow a simple and unambiguous assignment of donor and acceptor groups. The use of nuclear magnetic resonance spectroscopy is an elegant way to identify and experimentally characterize Me/π interactions in proteins without the need for arbitrary geometric descriptions or pre-existing three-dimensional structures. [ABSTRACT FROM AUTHOR]

Abstract: Using 31P solid-state NMR spectroscopy, anisotropy in the indirect 199Hg-31P spin–spin coupling tensor (ΔJ) for powdered [HgPCy3(OAc)2]2 (1) has been measured as 4700±300Hz. Zeroth-order regular approximation (ZORA) density functional theory (DFT) calculations, including scalar and spin-orbit relativistic effects, performed on 1 and a series of other related compounds show that ΔJ(199Hg, 31P) arises entirely from the ZORA Fermi-contact–spin-dipolar cross term. The calculations validate assumptions made in the spectral analysis of 1 and in previous determinations of ΔJ in powder samples, namely that J is axially symmetric and shares its principal axis system with the direct dipolar coupling tensor (D). Agreement between experiment and theory for various 199Hg, 31P spin–spin coupling anisotropies is reasonable; however, experimental values of 1 J(199Hg, 31P)iso are significantly underestimated by the calculations. The most important improvements in the agreement were obtained as a result of including more of the crystal lattice in the model used for the calculations, e.g., a change of 43% was noted for 1 J(199Hg, 31P)iso in [HgPPh3(NO3)2]2 depending on whether the two or three nearest nitrate ions are included in the model. Finally, we have written a computer program to simulate the effects of non-axial symmetry in J and of non-coincidence of the J and D on powder NMR spectra. Simulations clearly show that both of these effects have a pronounced impact on the 31P NMR spectrum of 199Hg–31P spin pairs, suggesting that the effects should be observable experimentally if a suitable compound can be identified. [Copyright &y& Elsevier]

Natural-abundance 43Ca solid-state NMR spectroscopy at 21.1 T and gauge-including projector-augmented-wave (GIPAW) DFT calculations are developed as tools to provide insight into calcium binding environments, with special emphasis on the calcium chemical shift (CS) tensor. The first complete analysis of a 43Ca solid-state NMR spectrum, including the relative orientation of the CS and electric field gradient (EFG) tensors, is reported for calcite. GIPAW calculations of the 43Ca CS and EFG tensors for a series of small molecules are shown to reproduce experimental trends; for example, the trend in available solid-state chemical shifts is reproduced with a correlation coefficient of 0.983. The results strongly suggest the utility of the calcium CS tensor as a novel probe of calcium binding environments in a range of calcium-containing materials. For example, for three polymorphs of CaCO3 the CS tensor span ranges from 8 to 70 ppm and the symmetry around calcium is manifested differently in the CS tensor as compared with the EFG tensor. The advantages of characterizing the CS tensor are particularly evident in very high magnetic fields where the effect of calcium CS anisotropy is augmented in hertz while the effect of second-order quadrupolar broadening is often obscured for 43Ca because of its small quadrupole moment. Finally, as an application of the combined experimental-theoretical approach, the solid-state structure of the vaterite polymorph of calcium carbonate is probed and we conclude that the hexagonal P63/mmc space group provides a better representation of the structure than does the orthorhombic Pbnm space group, thereby demonstrating the utility of 43Ca solid-state NMR as a complementary tool to X-ray crystallographic methods. [ABSTRACT FROM AUTHOR]

The results of a detailed systematic chlorine solid-state NMR study of several hydrochloride salts of amino acids implicated in chloride ion transport channel selectivity are reported. 35Cl and 37Cl NMR spectra have been obtained for stationary and/or magic-angle spinning powdered samples of the following compounds on 500 and/or 900 MHz spectrometers: DL-arginine HCI monohydrate, L-lysine HCI, L-serine HCI, L-glutamic acid HCI, L-proline HCI, L-isoleucine HCI, L-valine HCI, L-phenylalanine HCI, and glycine HCI. Spectral analyses provide information on the anisotropic properties and relative orientations of the chlorine electric field gradient and chemical shift (CS) tensors, which are intimately related to the local molecular and electronic structure. Data obtained at 900 MHz provide unique examples of the effects of CS anisotropy on the NMR spectrum of a quadrupolar nucleus. The range of chlorine quadrupolar coupling constants (CQ) measured, -6.42 to 2.03 MHz, demonstrates the sensitivity of this parameter to the chloride ion environment and suggests the applicability of chlorine solid-state NMR as a novel experimental tool for defining chloride binding environments in larger ion channel systems. Salts of hydrophobic amino acids are observed to tend to exhibit larger values of CQ than salts of hydrophilic amino acids. A simple model for rationalizing the observed trend in CQ is proposed. For salts for which neutron diffraction structures are available, we identify a quantum chemical method which reproduces experimental values of CQ with a root-mean-square deviation of 0.1 MHz and a correlation coefficient of 0.9998. On the basis of this, chlorine NMR tensors are predicted for the Cl- binding site in CIC channels. [ABSTRACT FROM AUTHOR]

Solid-state [sup 17]O NMR spectroscopy is employed to characterize powdered samples of known monoclinic and orthorhombic modifications of [sup 17]O-enriched triphenylphosphine oxide, Ph[sub 3]PO. Precise data on the orientationdependent [sup 17]O electric field gradient (EFG) and chemical shift (CS) tensors are obtained for both polymorphs. While the [sup 17]O nuclear quadrupolar coupling constants (C[sub Q]) are essentially identical for the two polymorphs (C[sub Q] = -4.59 ± 0.01 MHz (orthorhombic); C[sub Q] = -4.57 ± 0.01 MHz (monoclinic)), the spans (Ω) of the CS tensors are distinctly different (Ω = 135 ± 3 ppm (orthorhombic); Ω = 155 ± 5 ppm (monoclinic)). The oxygen CS tensor is discussed in terms of Ramsey's theory and the electronic structure of the phosphorus-oxygen bond. The NMR results favor the hemipolar σ-bonded R[sub 3]P[sup +]-O[sup -] end of the resonance structure continuum over the multiple bond representation. Indirect nuclear spin-spin (J) coupling between [sup 31]P and [sup 17]O is observed directly in [sup 17]O magicangle-spinning (MAS) NMR spectra as well as in [sup 31]P MAS NMR spectra. Ab initio and density-functional theory calculations of the [sup 17]O EFG, CS, and ¹J([sup 31]P,[sup 17]O) tensors have been performed with a variety of basis sets to complement the experimental data. This work describes an interesting spin system for which the CS, quadrupolar, J, and direct dipolar interactions all contribute significantly to the observed [sup 17]O NMR spectra and demonstrates the wealth of information which is available from NMR studies of solid materials. [ABSTRACT FROM AUTHOR]

Examines the structure of silver cyanide by solid-state multinuclear magnetic resonance spectroscopy. Linearity of polymeric chains; Domination of two-site model by indirect nuclear spin-spin coupling between [sup 109/107]Ag and [sup 12]C nuclei; Application of the zeroth-order regular approximation density functional theory calculation.

Among the interactions which govern NMR spectra, spin-spin coupling interactions provide the most direct form of structural information which is of interest to chemists. Dipolar coupling may be used to measure internuclear distances directly and J coupling may be used to identify bonding interactions and provide insights into the nature of the bonds. It is well known that the presence of a quadrupolar interaction reintroduces the dipolar interaction in spinning samples; however, similarly to the J coupling, this information is often lost if the observed nucleus is quadrupolar due to quadrupolar spectral broadening. Here we show for multiple spin pairs that double-rotation (DOR) NMR fully removes the effects of the quadrupolar interaction on the NMR spectrum leaving only the effects of dipolar and J couplings. We also demonstrate that the J coupling multiplets do not disappear for quadrupolar A2 spin pairs as they do for spin-1/2 nuclei. With DOR NMR, it is then straightforward to measure homonuclear J coupling constants between magnetically equivalent quadrupolar nuclei. A deeper understanding of the origins of the magnitudes and dominant mechanisms of J coupling for quadrupolar spin pairs in a series of related compounds is obtained by decomposing computed J coupling constants into their major molecular orbital contributions. [ABSTRACT FROM AUTHOR]

Highlights from the article: High-frequency dynamic nuclear polarization nuclear magnetic resonance (DNP NMR) spectroscopy is having a significant impact across disciplines by breaking down traditional barriers in solid-state NMR. Blank and coworkers report on SP 1 sp H polarization enhancement of up to 150 via DNP of a plasma-treated glucose powder.

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. [ABSTRACT FROM AUTHOR]

The article presents profile of scientist John Ripmeester. Topics include his enrollment at the University of British Columbia where he came across nuclear magnetic resonance (NMR) NMR spectroscopy; joining the Division of Chemistry at the U.S. National Research Council along with scientist Don Davidson; and his focus on clathrate hydrate research after his retirement.

The article features scientist John Ripmeester, who has made enormous impact on various research areas involving nuclear magnetic resonance (NMR) spectroscopy, porous materials, and clathrate hydrates. Topics include Ripmeester's experience of working for the paper industry in Canada, how his interest in chemistry has been developed, and his retirement from research in 2008 to focus on his role as head of the Functional Materials Program of the Steacie Institute for Molecular Sciences (SIMS).

Group 16 chalcogens potentially provide Lewis‐acidic σ‐holes, which are able to form attractive supramolecular interactions with electron rich partners through chalcogen bonds. Here, a multifaceted experimental and computational study of a large series of novel chalcogen‐bonded cocrystals, prepared using the principles of crystal engineering, is presented. Single‐crystal X‐ray diffraction studies reveal that dicyanoselenadiazole and dicyanotelluradiazole derivatives work as promising supramolecular synthons with the ability to form double chalcogen bonds with a wide range of electron donors including halides and oxygen‐ and nitrogen‐containing heterocycles. Extensive 77Se and 125Te solid‐state nuclear magnetic resonance spectroscopic investigations of cocrystals establish correlations between the NMR parameters of selenium and tellurium and the local chalcogen bonding geometry. The relationships between the electronic environment of the chalcogen bond and the 77Se and 125Te chemical shift tensors were elucidated through a natural localized molecular orbital density functional theory analysis. This systematic study of chalcogen‐bond‐based crystal engineering lays the foundations for the preparation of the various multicomponent systems and establishes solid‐state NMR protocols to detect these interactions in powdered materials. [ABSTRACT FROM AUTHOR]

Halogen bonding is the non-covalent interaction between the region of positive electrostatic potential associated with a covalently bonded halogen atom, named the σ-hole, and a Lewis base. Single-crystal X-ray diffraction structures are reported for a series of seven halogen-bonded cocrystals featuring 1,3,5-tris(iodoethynyl)-2,4,6-trifluorobenzene (1) as the halogen-bond donor, and bromide ions (as ammonium or phosphonium salts) as the halogen-bond acceptors: (1)·MePh3PBr, (1)·EtPh3PBr, (1)·acetonyl-Ph3PBr, (1)·Ph4PBr, (1)·[bis(4-fluorophenyl)methyl]triphenylphosphonium bromide, and two new polymorphs of (1)·Et3BuNBr. The cocrystals all feature moderately strong iodine-bromide halogen bonds. The crystal structure of pure [bis(4-fluorophenyl)methyl]triphenylphosphonium bromide is also reported. The results of a crystal engineering strategy of varying the size of the counter-cation are explored, and the features of the resulting framework materials are discussed. Given the potential utility of (1) in future crystal engineering applications, detailed NMR analyses (in solution and in the solid state) of this halogen-bond donor are also presented. In solution, complex 13C and 19F multiplets are explained by considering the delicate interplay between various J couplings and subtle isotope shifts. In the solid state, the formation of (1)·Et3BuNBr is shown through significant 13C chemical shift changes relative to pure solid 1,3,5-tris(iodoethynyl)-2,4,6-trifluorobenzene. [ABSTRACT FROM AUTHOR]

Halogen bonding to phosphorus atoms remains uncommon, with relatively few examples reported in the literature. Here, the preparation and investigation of the cocrystal bis(dicyclohexylphenylphosphine)(1,6-diiodoperfluorohexane) by X-ray crystallography and solid-state multinuclear magnetic resonance spectroscopy is described. The crystal structure features two crystallographically unique C--I...P halogen bonds [dI...P = 3.090 (5) A, 3.264 (5) A ] and crystallographic disorder of one of the 1,6-diiodoperfluorohexane molecules. The first of these is the shortest and most linear I...P halogen bond reported to date. 13C, 19F, and 31P magic angle spinning solid-state NMR spectra are reported. A 31P chemical shift change of -7.0 p.p.m. in the cocrystal relative to pure dicyclohexylphenylphosphine, consistent with halogen bond formation, is noted. This work establishes iodoperfluoroalkanes as viable halogen bond donors when paired with phosphorus acceptors, and also shows that dicyclohexylphenylphosphine can act as a practical halogen bond acceptor. [ABSTRACT FROM AUTHOR]

A highly cross-linked microporous organic network with imine linkers was prepared by condensation of tetrakis(4-aminophenyl)methane with terephthaldehyde. Gas adsorption studies indicate that the material exhibits permanent microporosity, and guest exchange experiments demonstrate that small molecules can diffuse into the network. Postsynthetic modification of this microporous network was achieved by treatment with borane in THF, which reduced the imine groups to the corresponding amines as shown by IR and 13C CP-MAS solid-state NMR spectroscopy. The resulting material showed enhanced resistance to acidic hydrolysis compared with the imine precursor, and retained its ability to absorb guest molecules. The amine network was amenable to further postsynthetic modifications. Specifically, acetylation of this network using acetic anhydride was demonstrated. [ABSTRACT FROM AUTHOR]

Field‐stepped NMR spectroscopy at up to 36 T using the series‐connected hybrid (SCH) magnet at the U.S. National High Magnetic Field Laboratory is demonstrated for acquiring ultra‐wideline powder spectra of nuclei with very large quadrupolar interactions. Historically, NMR evolved from the continuous‐wave (cw) field‐swept method in the early days to the pulsed Fourier‐transform method in the modern era. Spectra acquired using field sweeping are generally considered to be equivalent to those acquired using the pulsed method. Here, it is shown that field‐stepped wideline spectra of half‐integer spin quadrupolar nuclei acquired using WURST/CPMG methods can be significantly different from those acquired with the frequency‐stepped method commonly used with superconducting magnets. The inequivalence arises from magnetic field‐dependent NMR interactions such as the anisotropic chemical shift and second‐order quadrupolar interactions; the latter is often the main interaction leading to ultra‐wideline powder patterns of half‐integer spin quadrupolar nuclei. This inequivalence needs be taken into account to accurately and correctly determine the quadrupolar coupling and chemical shift parameters. A simulation protocol is developed for spectral fitting to facilitate analysis of field‐stepped ultra‐wideline NMR spectra acquired using powered magnets. A MATLAB program which implements this protocol is available on request. [ABSTRACT FROM AUTHOR]

Frontispiece: Double Chalcogen Bonds: Crystal Engineering Stratagems via Diffraction and Multinuclear Solid-State Magnetic Resonance Spectroscopy Keywords: chalcogen bonds; crystal engineering; dicyanoselenadiazole; dicyanotelluradiazole; molecular orbital analysis; solid-state NMR Chalcogen bonds, crystal engineering, dicyanoselenadiazole, dicyanotelluradiazole, molecular orbital analysis, solid-state NMR. [Extracted from the article]

Abstract: Halogen bonding is an increasingly important tool in crystal engineering, and measuring its influence on the local chemical and electronic environment is necessary to fully understand this interaction. Here, we present a systematic crystallographic and solid‐state NMR study of self‐complementary halogen‐bonded frameworks built from the halide salts (HCl, HBr, HI, HI3) of 2‐iodoethynylpyridine and 3‐iodoethynylpyridine. A series of single crystal X‐ray structures reveals the formation of discrete charged dimers in the solid state, directed by simultaneous X−⋅⋅⋅H−N+ hydrogen bonds and C−I⋅⋅⋅X− halogen bonds (X=Cl, Br, I). Each compound was studied using multinuclear solid‐state magnetic resonance spectroscopy, observing 1H to investigate the hydrogen bonds and 13C, 35Cl, and 79/81Br to investigate the halogen bonds. A natural localized molecular orbital analysis was employed to help interpret the experimental results. 1H SSNMR spectroscopy reveals a decrease in the chemical shift of the proton participating in the hydrogen bond as the halogen increases in size, whereas the 13C SSNMR reveals an increased 13C chemical shift of the C−I carbon for C−I⋅⋅⋅X− relative to C−I⋅⋅⋅N halogen bonds. Additionally, 35Cl and 79/81Br SSNMR, along with computational results, have allowed us to compare the C−I⋅⋅⋅X− halogen bond involving each halide in terms of NMR observables. Due to the isostructural nature of these compounds, they are ideal cases for experimentally assessing the impact of different halogen bond acceptors on the solid‐state NMR response. [ABSTRACT FROM AUTHOR]

In situ31P solid-state NMR studies of halogen bond formation between triphenylphosphine oxide and para-diiodotetrafluorobenzene provide insights into the cocrystallisation process and provide an estimate of the activation energy. The effects of temperature, magic-angle spinning speed, and initially added liquid on the reaction rate and mechanism have been investigated. [ABSTRACT FROM AUTHOR]

Protein structure and function is dependent on myriad noncovalent interactions. Direct detection and characterization of these weak interactions in large biomolecules, such as proteins, is experimentally challenging. Herein, we report the first observation and measurement of long-range 'through-space' scalar couplings between methyl and backbone carbonyl groups in proteins. These J couplings are indicative of the presence of noncovalent C−H⋅⋅⋅π hydrogen-bond-like interactions involving the amide π network. Experimentally detected scalar couplings were corroborated by a natural bond orbital analysis, which revealed the orbital nature of the interaction and the origins of the through-space J couplings. The experimental observation of this type of CH⋅⋅⋅π interaction adds a new dimension to the study of protein structure, function, and dynamics by NMR spectroscopy. [ABSTRACT FROM AUTHOR]

An overview of the role of solid-state nuclear magnetic resonance (SSNMR) spectroscopy in the field of crystal engineering is provided. NMR methodologies often provide insights into the structure and dynamics of solid materials which would otherwise be unavailable by X-ray diffraction. More generally, NMR crystallographic structure solutions or refinement approaches seek to incorporate available data from all sources, including the results of density functional theory calculations and diffraction data. This Highlight article discusses the state of the field through a recapitulation of relevant theory and selected applications from the literature. Specific topics covered include NMR structure refinement, polymorph identification and differentiation, non-covalent interactions, and the role of dynamics. [ABSTRACT FROM AUTHOR]

The dramatic reactivity difference between the Grubbs metathesis catalysts and their resting-state methylidene derivatives was probed in an integrated crystallographic, solid-state NMR and localized molecular orbital analysis study. A principal focus was the second-generation Grubbs system RuCl2(H2IMes)(PCy3)(=CHR) (GII, R = Ph; GIIm, R = H); supporting studies were carried out with the first-generation species RuCl2(PCy3)2(=CHR) (GI, GIm). The compiled rate constants for PCy3 dissociation demonstrate the limited lability of the methylidene complexes (e.g., ca. 275-fold lower for GIIm than GII and nearly 2000 times lower for the IMes analogue GIIm'). This is important because it impedes catalyst re-entry from the resting state into the active cycle. The 31P chemical shift (CS) tensors for the PCy3 ligand exhibited the expected changes (i.e., those characteristic of an increased Ru-P orbital interaction) in GIIm relative to GII, as did GIm vs GI. Greater insight was offered by the 13C CS tensors. Whereas calculations on truncated models predict significant differences in 13C CS tensor values for GII compared with GIIm, the experimental values are equivalent, implying a compensating effect that weakens the Ru=C interaction in the benzylidene complex. Published X-ray crystallographic parameters for GII and GI reveal that one chloride ligand is displaced below the basal plane by steric interactions with the benzylidene phenyl group, an effect absent in GIIm and GIm. During PCy3 loss from the [Ru]=CHPh systems, established processes of alkylidene rotation transform Ph-Cl repulsion into Ph-PCy3 repulsion. Displacing the PCy3 ligand below the plane does not relieve this conflict, instead incurring steric interactions with the H2IMes ligand. Enhanced PCy3 lability in the benzylidene complexes, relative to their methylidene analogues, is hence proposed to originate in the steric pressure exerted by the Ph substituent. [ABSTRACT FROM AUTHOR]

Borinium cations (R2B+) are of particular fundamental and applied interest in part due to their pronounced Lewis acidity which enables unique chemical transformations. Solid-state NMR spectroscopy of magic-angle spinning and stationary powdered samples of the dicoordinate boron cation in the recently reported dimesitylborinium tetrakis(pentafluorophenyl)borate compound (Shoji et al. Nature Chem. 2014, 6, 498) is applied to characterize the 11B electric field gradient (EFG) and chemical shift (CS) tensors. The experimental data are consistent with linear C--B+--C geometry. The 11B quadrupolar coupling constant, 5.44 ± 0.08 MHz, and the span of the CS tensor, 130 ± 1 ppm, are both particularly large relative to literature data for a variety of boron functional groups, and represent the first such data for the linear C--B+--C borinium moiety. The NMR data are similar to those for the neutral tricoordinate analogue, trimesitylborane, but contrast with those of the Cp*2B+ cation. Quantum chemical calculations are applied to provide additional insights into the relationship between the NMR observables and the molecular and electronic structure of the dimesitylborinium cation. [ABSTRACT FROM AUTHOR]

Noncovalent interactions play a ubiquitous role in the structure, stability, and reactivity of a wade range of molecular and ionic cocrystals, pharmaceuticals, materials, and biomolecules. The halogen bond continues to be the focus of much attention, due in part to its strength and unique directionality. Here, we report a multifaceted experimental and computational study of halogen bonds in the solid state. A series of cocrystals of three different diiodobenzene molecules and various onium halide (Cl- or Br-) salts, designed to exhibit moderately strong halogen bonds (C-I···X -) in the absence of competing hydrogen bonds, has been prepared and characterized by single-crystal X-ray diffraction. Interestingly, a wide range of geometries about the halide anion are observed. 35/37Cl and 79/81Br solid state NMR spectroscopy is applied to characterize the nuclear quadrupolar coupling constants (CQ) and asymmetry parameters (ηQ) for the halogen-bonded anions at the center of bonding environments ranging from approximately linear to distorted square planar to octahedral. The relationship between the halogen bond environment and the quadrupolar parameters is elucidated through a natural localized molecular orbital (NLMO) analysis in the framework of density functional theory (DFT). These calculations reveal that the lone pair type orbitals on the halogen-bonded anion govern the magnitude and orientation of the quadrupolar tensor as the geometry about the anion is systematically altered. In - C - I··· X-··· I - C - environments, the value of ηQ is well-correlated to the I···X-···I angle. 13C NMR and DFT calculations show a correlation between chemical shifts and halogen bond strength (through the C-I distance) in o-diiodotetrafluorobenzene cocrystals. Overall, this work provides a chemically intuitive understanding of the connection between the geometry and electronic structure of halogen bonds and various NMR parameters with the aid of NLMO analysis. [ABSTRACT FROM AUTHOR]

A series of calcium and strontium complexes featuring aryl carboxylate ligands has been prepared and characterized by alkaline-earth (43Ca and 87Sr) solid-state NMR experiments in a magnetic field of 21.1 T. In the 11 compounds studied as part of this work, a range of coordination motifs are observed including nitrogen atom binding to Ca2+ and Sr2+, a binding mode which has not been investigated previously by 43Ca or 87Sr solid-state NMR. 43Ca isotopic enrichment has enabled the full characterization of the 43Ca electric field gradient (EFG) and chemical shift tensors of the two calcium sites in calcium p-aminosalicylate (Ca(pams)), where both NMR interactions are affected by the presence of a nitrogen atom in the first coordination sphere of one of the metal sites. The 43Ca isotropic chemical shift is sensitive to the Ca-N distance as exemplified by the NMR parameters of a second form of Ca(pams) and density functional theory (DFT) calculations. Studies of the strontium analogue, Sr(pams), confirm a similar sensitivity of the 87Sr EFG tensor to the presence or absence of nitrogen in the first coordination sphere. To our knowledge, this is the first systematic 87Sr NMR study of strontium complexes featuring organic ligands. The |CQ(87Sr)| values are found to be sensitive to the coordination number about Sr2+. In general, this work has also established a larger data set of reliable experimental |CQ(43Ca)| values which correlate well with those obtained using gauge-including projector-augmented-wave (GIPAW) DFT calculations. It is found that the use of a recently recommended quadrupole moment for 43Ca, -44.4 mbarn, improves the agreement with experimental values. This contribution lays the groundwork for the interpretation of 43Ca and 87Sr NMR spectra of more challenging systems, particularly where nitrogen-alkaline earth metal bonding is occurring. [ABSTRACT FROM AUTHOR]

Although the understanding of intermolecular interactions, such as hydrogen bonding, is relatively well-developed, many additional weak interactions work both in tandem and competitively to stabilize a given crystal structure. Due to a wide array of potential applications, a substantial effort has been invested in understanding the halogen bond. Here, we explore the utility of multinuclear (13C, 14/15N, 19F, and 127I) solid-state magnetic resonance experiments in characterizing the electronic and structural changes which take place upon the formation of five halogen-bonded co-crystalline product materials. Single-crystal X-ray diffraction (XRD) structures of three novel co-crystals which exhibit a 1:1 stoichiometry between decamethonium diiodide (i.e., [(CH3)3N+(CH2)10N+(CH3)3][2 I−]) and different para-dihalogen-substituted benzene moieties (i.e., p-C6X2Y4, X=Br, I; Y=H, F) are presented. 13C and 15N NMR experiments carried out on these and related systems validate sample purity, but also serve as indirect probes of the formation of a halogen bond in the co-crystal complexes in the solid state. Long-range changes in the electronic environment, which manifest through changes in the electric field gradient (EFG) tensor, are quantitatively measured using 14N NMR spectroscopy, with a systematic decrease in the 14N quadrupolar coupling constant ( CQ) observed upon halogen bond formation. Attempts at 127I solid-state NMR spectroscopy experiments are presented and variable-temperature 19F NMR experiments are used to distinguish between dynamic and static disorder in selected product materials, which could not be conclusively established using solely XRD. Quantum chemical calculations using the gauge-including projector augmented-wave (GIPAW) or relativistic zeroth-order regular approximation (ZORA) density functional theory (DFT) approaches complement the experimental NMR measurements and provide theoretical corroboration for the changes in NMR parameters observed upon the formation of a halogen bond. [ABSTRACT FROM AUTHOR]

Abstract: Recent progress in the development and application of signal enhancement methods for NMR of quadrupolar nuclei in solids is presented. First, various pulse schemes for manipulating the populations of the satellite transitions in order to increase the signal of the central transition (CT) in stationary and rotating solids are evaluated (e.g., double-frequency sweeps, hyperbolic secant pulses). Second, the utility of the quadrupolar Carr–Purcell–Meiboom–Gill (QCPMG) and WURST-QCPMG pulse sequences for the rapid and efficient acquisition of particularly broad CT powder patterns is discussed. Third, less frequently used experiments involving polarization transfer from abundant nuclear spins (cross-polarization) or from unpaired electrons (dynamic nuclear polarization) are assessed in the context of recent examples. Advantages and disadvantages of particular enhancement schemes are highlighted and an outlook on possible future directions for the signal enhancement of quadrupolar nuclei in solids is offered. [Copyright &y& Elsevier]

We report on the investigation of sodium coordination environments with solid-state 23Na nuclear magnetic resonance (NMR) spectroscopy of various hydrates and solvates of sodium naproxen (SN), a commercially available anti-inflammatory drug sold over the counter as Aleve®, among other names. The 23Na quadrupolar coupling constant is found to change significantly depending on the hydration state, and subtle changes in oxygen coordination environment about the sodium cations were apparent in the NMR spectra. High-resolution double-rotation NMR experiments are also performed on powdered samples to obtain solution-like 23Na NMR spectra. Our attempts at crystallizing various solvates of SN have led to the characterization of the first crystal structure for the heminonahydrated form. The composition of commercial SN is also investigated and it is shown that Aleve® is composed of approximately 80% monohydrate solvate. Density-functional theory calculations, using the gauge-including projector-augmented-wave formalism, allow for the assignment of 23Na NMR peaks to specific sodium sites in the reported X-ray crystal structure. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2930-2940, 2012 [ABSTRACT FROM AUTHOR]

Abstract: While the synthetic utility and reactivity of the so-called “GaI” species is reasonably well established, its exact composition remains unknown. Using primarily multinuclear magnetic resonance techniques (and supported with powder X-ray diffraction measurements), we offer some new insights into the composition of “GaI”. Using 127I nuclear quadrupole resonance (NQR) experiments, it is clearly demonstrated that gallium diiodide (GaI2) is a significant component of this material, while GaI3 is not. This finding is in contrast with a prior literature account, which noted that Ga2I3 (i.e., one equivalent of GaI3 per equivalent of Ga metal) was present in significant amounts. Additional solid-state nuclear magnetic resonance (SSNMR) experiments using the 69/71Ga probe nuclei in multiple magnetic fields clearly establish, via its diagnostic Knight-shifted resonance, the presence of Ga0 metal, which is in agreement with prior literature. Taken together, a composition may be tentatively offered: that “GaI” is, to a large extent, two equivalents of Ga0 metal with two equivalents of GaI2, where the latter is composed of Ga+ and ions. This composition may be represented as [Ga0]2[Ga]+[GaI4]−. [Copyright &y& Elsevier]

A series of monohaloanilinium halides exhibiting weakhalogen bonding(XB) has been prepared and characterized by 35Cl, 81Br, and 127I solid-state nuclear magnetic resonance(SSNMR) spectroscopy in magnetic fields of up to 21.1 T. The quadrupolarand chemical shift (CS) tensor parameters for halide ions (Cl–, Br–, I–) whichact as electron density donors in the halogen bonds of these compoundsare measured to provide insight into the possible relationship betweenhalogen bonding and NMR observables. The NMR data for certain seriesof related compounds are strongly indicative of when such compoundspack in the same space group, thus providing practical structuralinformation. Careful interpretation of the NMR data in the contextof novel and previously available X-ray crystallographic data, andnew gauge-including projector-augmented-wave density functional theory(GIPAW DFT) calculations has revealed several notable trends. Whena series of related compounds pack in the same space group, it hasbeen possible to interpret trends in the NMR data in terms of thestrength of the halogen bond. For example, in isostructural series,the halide quadrupolar coupling constant was found to increase asthe halogen bond weakens. In the case of a series of haloaniliniumbromides, the 81Br isotropic chemical shift and CS tensorspan both decrease as the bromide–halogen XB is weakened. Thesetrends were reproduced using both GIPAW DFT and cluster-model calculationsof the bromide ion magnetic shielding tensor. Such trends are particularlyexciting given the well-known role that NMR has played historicallyin the characterization of hydrogen bonding. [ABSTRACT FROM AUTHOR]

The results of a 35/37Cl solid-state nuclear magnetic resonance (SSNMR) study of the 1-butyl-3-methylimidazolium chloride complex of meso-octamethylcalix[4]pyrrole ( 1) are reported. Line shapes obtained from magic-angle-spinning and stationary powder samples collected at 9.4 and 21.1 T are analyzed to provide the 35/37Cl quadrupolar tensor and chemical shift (CS) tensor and their relative orientation. The relatively high symmetry of the chloride ion coordination environment is manifested in the small value of the quadrupole coupling constant, CQ(35Cl) = 1.0 MHz. The isotropic chemical shift of 120 ppm (with respect to NaCl(s)) is at the upper edge of the typical range seen for organic hydrochlorides. Consideration of chemical shift anisotropy (span, Ω = 50 ppm) and non-coincidence of the quadrupolar and CS tensors were essential to properly simulate the experimental spectra. The utility of gauge-including projector-augmented wave density functional theory (GIPAW-DFT) calculations of chlorine quadrupolar and CS tensors in organic chlorides was explored by validation against available benchmark experimental data for solid amino acid hydrochlorides. The calculations are shown to systematically overestimate the value of the 35Cl quadrupole coupling constant. Additional calculations on various hydrated and solvated models of 1 are consistent with a structure in which solvent and water of hydration are absent. [ABSTRACT FROM AUTHOR]

A family of molecular heptacadmium carboxylate clusters templated inside [3 + 3] Schiff base macrocycles has been isolated and studied by variable temperature solution and solid-state NMR spectroscopy, single-crystal X-ray diffraction (SCXRD), and density functional theory (DFT) calculations. These metallocavitand cluster complexes adopt bowl-shaped structures, induced by metal coordination, giving rise to interesting host-guest and supramolecular phenomena. Specifically, dimerization of these metallocavitands yields capsules with vacant coordination and hydrogen-bonding sites accessible to encapsulated guests. Strong host-guest interactions explain the exceptionally high packing coefficient (0.80) observed for encapsulated N, N-dimethylformamide (DMF). The guest-accessible hydrogen-bonding sites arise from an unusual μ3-OH ligand bridging three cadmium ions. Thermodynamic and kinetic studies show that dimerization is an entropy-driven process with a highly associative mechanism. In DMF the exchange rate of peripheral cluster supporting carboxylate ligands is intrinsically linked to the rate of dimerization and these two seemingly different events have a common rate-determining step. Investigation of guest dynamics with solid-state ²H NMR spectroscopy revealed 3-fold rotation of an encapsulated DMF molecule. These studies provide a solid understanding of the host-guest and dynamic properties of a new family of metallocavitands and may help in designing new supramolecular catalysts and materials. [ABSTRACT FROM AUTHOR]

Transactivation-response element (TAR) is a stable stem-loop structure of HIV RNA, which plays a crucial role during the life cycle of the virus. The apical loop of TAR acts as a binding site for essential cellular cofactors required for the replication of HIV. High-affinity aptamers directed against the apical loop of TAR have been identified by the SELEX approach. The RNA aptamers with the highest affinity for TAR fold as hairpins and form kissing complexes with the targeted RNA through loop-loop interactions. The aptamers with the strongest binding properties all possess a GA base pair combination at the loop-closing position. Using liquid-crystal NMR methodology, we have obtained a structural model in solution of a TAR-aptamer kissing complex with an unprecedented accuracy. This high-resolution structure reveals that the GA base pair is unilaterally shifted toward the 5′ strand and is stabilized by a network of intersugar hydrogen bonds. This specific conformation of the GA base pair allows for the formation of two supplementary stable base-pair interactions. By systematic permutations of the loop-closing base pair, we establish that the identified atomic interactions, which form the basis for the high stability of the complex, are maintained in several other kissing complexes. This study rationalizes the stabilizing role of the loop-closing GA base pairs in kissing complexes and may help the development or improvement of drugs against RNA loops of viruses or pathogens as well as the conception of biochemical tools targeting RNA hairpins involved in important biological functions. [ABSTRACT FROM AUTHOR]

• Solid-state NMR provides a nuclear site specific probe of non-covalent bonds. • Applications to hydrogen bonds, halogen bonds, tetrel bonds, and pnictogen bonds are discussed. • NMR parameters correlate with structural features of the non-covalent bonds. • Dynamic processes may be probed through relaxation time constant measurements. We review applications of solid-state NMR spectroscopy for the analysis of element-based non-covalent interactions, with an emphasis on developments since 2009. The review is presented in five parts: 1. General Introduction; 2. Basic Principles of Solid-State NMR; 3. Applications to Hydrogen Bonding; 4. Applications to Halogen Bonding; 5. Applications to Other Element-Based Interactions (Tetrel, Pnictogen, Chalcogen). Chemical shifts, quadrupolar couplings, dipolar couplings, and J couplings are the main NMR parameters used to study non-covalent interactions in solids. Correlations with structural features are described. The utility of relaxation time constants in probing dynamic processes is discussed. In addition to covering standard solid-state NMR studies of powdered samples, applications of nuclear quadrupole resonance NQR and single-crystal NMR are discussed. It is clear that the vast array of magnetic resonance techniques available affords numerous important insights into a wide range of non-covalent interactions in solids. [ABSTRACT FROM AUTHOR]

Keywords: halogen bonding; hydrogen bonding; solid-state NMR; crystal engineering; X-ray crystallography The identity and phase purity of this and five related anion-coordinated architectures based on 3-iodoethynylpyridine and 3-iodoethynylbenzoic acid halogen bond donors are established with powder X-ray diffraction and multinuclear solid-state magnetic resonance spectroscopy. Halogen bonding, hydrogen bonding, solid-state NMR, crystal engineering, X-ray crystallography. [Extracted from the article]