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Halogen bonding is a noncovalent interaction between the electrophilic region of a halogen (σ-hole) and an electron donor. We report a crystallographic and structural analysis of halogen-bonded compounds by applying a combined X-ray diffraction (XRD) and solid-state nuclear magnetic resonance (SSNMR) approach. Single-crystal XRD was first used to characterize the halogen-bonded cocrystals formed between two fluorinated halogen-bond donors (1,4-diiodotetrafluorobenzene and 1,3,5-trifluoro-2,4,6-triiodobenzene) and several nitrogen-containing heterocycles (acridine, 1,10-phenanthroline, 2,3,5,6-tetramethylpyrazine, and hexamethylenetetramine). New structures are reported for the following three cocrystals, all in the P21/ c space group: acridine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C6F3I3·C13H9N, 1,10-phenanthroline-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C6F3I3·C12H8N2, and 2,3,5,6-tetramethylpyrazine-1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C6F3I3·C8H12N2. 13C and 19F solid-state magic-angle spinning (MAS) NMR is shown to be a convenient method to characterize the structural features of the halogen-bond donor and acceptor, with chemical shifts attributable to cocrystal formation observed in the spectra of both nuclides. Cross polarization (CP) from 19F to 13C results in improved spectral sensitivity in characterizing the perfluorinated halogen-bond donor when compared to conventional 1H CP. Gauge-including projector-augmented wave density functional theory (GIPAW DFT) calculations of magnetic shielding constants, along with optimization of the XRD structures, provide a final set of structures in best agreement with the experimental 13C and 19F chemical shifts. Data for carbons bonded to iodine remain outliers due to well-known relativistic effects. [ABSTRACT FROM AUTHOR]

Studies of three related CdII systems (a discrete [CdII2] unit, a one-dimensional [CdII2]n coordination polymer and a CdII-based MOF) all derived from the ligand 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine, reveal an exceptionally rare example of 113Cd–113Cd J coupling in the polymer that is detectable by solid-state NMR (2JCd–Cd = ∼65 Hz). [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]

Multiple bonding between atoms is of ongoing fundamental and applied interest. Here, we report a multinuclear (1H, 13C, and 71Ga) solid-state magnetic resonance spectroscopic study of digallium compounds which have been proposed, albeit somewhat controversially, to contain single, double, and triple Ga−Ga bonds. Of particular relevance to the nature of these bonds, we have carried out two-dimensional 71Ga J/ D-resolved NMR experiments which provide a direct measurement of J(71Ga,71Ga) spin-spin coupling constants across the gallium−gallium bonds. When placed in the context of clear-cut experimental data for analogous singly, doubly, and triply bonded carbon spin pairs or boron spin pairs, the 71Ga NMR data clearly support the notion of a different bonding paradigm in the gallium systems. Our findings are consistent with an increasing role across the purported gallane-gallene-gallyne series for classical and/or slipped π-type bonding orbitals. [ABSTRACT FROM AUTHOR]

Coordinatively unsaturated FeIII metal sites were successfully incorporated into the iconic MOF-5 framework. This new structure, FeIII-iMOF-5, is the first example of an interpenetrated MOF linked through intercalated metal ions. Structural characterization was performed with single-crystal and powder XRD, followed by extensive analysis by spectroscopic methods and solid-state NMR, which reveals the paramagnetic ion through its interaction with the framework. EPR and Mössbauer spectroscopy confirmed that the intercalated ions were indeed FeIII, whereas DFT calculations were employed to ascertain the unique pentacoordinate architecture around the FeIII ion. Interestingly, this is also the first crystallographic evidence of pentacoordinate ZnII within the MOF-5 SBU. This new MOF structure displays the potential for metal-site addition as a framework connector, thus creating further opportunity for the innovative development of new MOF materials. [ABSTRACT FROM AUTHOR]

We report the preparation and characterisation of a cocrystal of triphenylphosphine with 1,3,5-trifluoro-2,4,6-triiodobenzene. The structure features a rare example of phosphorus acting as a halogen bond acceptor. [ABSTRACT FROM AUTHOR]

Coordinatively unsaturated FeIII metal sites were successfully incorporated into the iconic MOF-5 framework. This new structure, FeIII- iMOF-5, is the first example of an interpenetrated MOF linked through intercalated metal ions. Structural characterization was performed with single-crystal and powder XRD, followed by extensive analysis by spectroscopic methods and solid-state NMR, which reveals the paramagnetic ion through its interaction with the framework. EPR and Mössbauer spectroscopy confirmed that the intercalated ions were indeed FeIII, whereas DFT calculations were employed to ascertain the unique pentacoordinate architecture around the FeIII ion. Interestingly, this is also the first crystallographic evidence of pentacoordinate ZnII within the MOF-5 SBU. This new MOF structure displays the potential for metal-site addition as a framework connector, thus creating further opportunity for the innovative development of new MOF materials. [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]

17O solid-state NMR studies of waters of hydration in crystalline solids are presented. The 17O quadrupolar coupling and chemical shift (CS) tensors, and their relative orientations, are measured experimentally at room temperature for α-oxalic acid dihydrate, barium chlorate monohydrate, lithium sulfate monohydrate, potassium oxalate monohydrate, and sodium perchlorate monohydrate. The 17O quadrupolar coupling constants ( CQ) range from 6.6 to 7.35 MHz and the isotropic chemical shifts range from -17 to 19.7 ppm. The oxygen CS tensor spans vary from 25 to 78 ppm. These represent the first complete CS and electric field gradient tensor measurements for water coordinated to metals in the solid state. Gauge-including projector-augmented wave density functional theory calculations overestimate the values of CQ, likely due to librational dynamics of the water molecules. Computed CS tensors only qualitatively match the experimental data. The lack of strong correlations between the experimental and computed data, and between these data and any single structural feature, is attributed to motion of the water molecules and to the relatively small overall range in the NMR parameters relative to their measurement precision. Nevertheless, the isotropic chemical shift, quadrupolar coupling constant, and CS tensor span clearly differentiate between the samples studied and establish a 'fingerprint' 17O spectral region for water coordinated to metals in solids. [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]

2D polymeric water–chloride/bromide sheets comprising a unique pentagon-like dichloride/dibromide-trihydrate cluster in the solid state have been observed as [Co(bpca)2]+ (bpca = bis(2-pyrimidylcarbonyl)amidate anion) counterions. Both compounds were obtained by the reaction of 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine (TPymT) with CoX2 (X = Cl, Br) in water. Solid-state multinuclear magnetic resonance spectroscopy and XRD provide insight into the structures. [ABSTRACT FROM AUTHOR]

A thorough investigation of solid-state NMR signal enhancement schemes and high-resolution techniques for application to the spin-7/2 43Ca nuclide are presented. Signal enhancement experiments employing double frequency sweeps, hyperbolic secant pulses, and rotor-assisted population transfer, which manipulate the satellite transitions of half-integer quadrupolar nuclei to polarize the central transition (m = +1/2 ... -1/2), are carried out on four well-characterized 43Ca isotopically enriched calcium salts: Ca(NO3)2, Ca(OD)2, CaSO4-2H2O, and Ca(OAc)2-H2O. These results, in conjunction with numerical simulations of 43Ca NMR spectra under magic-angle spinning conditions, are used to identify the technique that provides the most uniform (or quantitative) polarization enhancement as well as the largest signal enhancement factors independent of size of the 43Ca quadrupolar coupling constant, which is the most significant source of resonance broadening in 43Ca NMR spectra. These samples are further investigated using 43Ca double-rotation NMR spectroscopy to yield isotropic, or solution-like, NMR spectra with exquisite resolution. In addition, three unique calcium sites are resolved for the hemihydrated form of calcium acetate (unknown structure), Ca(OAc)2-0.5H2O, with double-rotation NMR, whereas the more common, but more time-consuming, multiple quantum magic-angle spinning technique only clearly resolves two calcium sites. The results shown herein will be useful for other NMR spectroscopists attempting to acquire 43Ca solid-state NMR data for unknown and more complex materials with a higher degree of both sensitivity and resolution. [ABSTRACT FROM AUTHOR]

A unique HgII coordination polymer has been synthesized through the reaction of 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine (TPymT) with a stoichiometric mixture of HgCl2 and NH4NCS, thus leading to the formation of a 1D polymeric heteroleptic hybrid material [{Hg(NCS)2}2TPymT] n ( 1). Two coordination pockets of TPymT in 1 are each coordinated to two HgII cations in an unprecedented 2,2′-bipyridine-like mode. [ABSTRACT FROM AUTHOR]

Halogen bonds constitute an important and topical class of non-covalent interaction. We report a combined X-ray diffraction, multinuclear (77Se, 31P, 13C) solid-state magnetic resonance, and computational study of a series of crystalline triphenylphosphine selenide-iodoperfluorobenzene complexes which feature P=Se⋯I-C halogen bonds. Selenium-77 chemical shifts increase due to halogen bonding with iodine and correlate with the P=Se distance, which in turn correlates with the strength of the halogen bond. (77Se, 31P) coupling constants increase in magnitude as the halogen bond weakens. This observation is understood a natural localized molecular orbital (NLMO) DFT approach which shows that contributions from the selenium lone pair orbital tend to dominate both the magnitude and trends in (77Se, 31P), with the selenium-phosphorus bonding orbital being the second largest contributor. This work suggests that couplings measured NMR spectroscopy may play an important role in the characterization of halogen bonds, in clear analogy with their role in the characterization of hydrogen bonds. [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]

Reaction of 2,4,6-tris(2-pyrimidyl)-1,3,5-triazine (TPymT) with Pb(NO3)2 in aqueous medium leads to the formation of a mixture of two pseudopolymorphs, {[Pb2(TPymT)(H2O)(NO3)4]·H2O}n, 1 and [Pb2(TPymT)(NO3)4]n, 2, where TPymT molecules are coordinated with two PbII ions in a bridging bis-terpyridine fashion. We demonstrate that fast evaporation of the solvent leads exclusively to the formation of 1, while 2 was formed upon slow evaporation. The two pseudopolymorphs can be interconverted by dissolving in water upon heating and controlling the evaporation rate. [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]

A large fraction of hydrogens in proteins and nucleic acids is of the methylene type. Their detailed study, however, in terms of structure and dynamics by NMR spectroscopy is hampered by their fast relaxation properties, which give rise to low sensitivity and resolution. It is demonstrated that six different relaxation interference processes, involving 1H-13H and 1H-1H dipolar interactions and 1H and 13C chemical shift anisotropy, can be used simultaneously to mitigate these problems effectively. The approach is applicable to the majority of NMR experiments commonly used to study side chain and backbone conformation. For proteins, its efficiency is evaluated quantitatively for two samples: the third IgG-binding domain from Streptococcal Protein G and the protein calmodulin complexed with a 26-residue target peptide. Gains in both resolution and sensitivity by up to factors of 3.2 and 2.0, respectively, are observed for Gly residues at high magnetic field strengths, but even at much lower fields gains remain substantial. The resolution enhancement obtained for methylene groups makes possible a detailed analysis of spectral regions commonly considered inaccessible due to spectral crowding. For DNA, the high resolution now obtainable for C5' sites permits an H5'/H5"-based sequential NOE assignment procedure, complementary to the conventional base-H1'/H2'/H2" pathway. [ABSTRACT FROM AUTHOR]

Context: Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects. Objective: To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment. Design, Setting, and Patients: Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment. Interventions: Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group. Main Outcome Measure: Mean percentage change in VASPI score from baseline to the end of the initial titration period. Results: Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P = .63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P = .18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved comp... [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]

Invited for this month's cover picture is the group of Professor David Bryce at the University of Ottawa. The cover picture shows a stylized depiction of the mechanochemical halogen‐bond induced cocrystallization of 3‐iodoethynylpyridine with tetraphenylphosphonium bromide. Read the full text of their Full Paper at 10.1002/open.201900194. [ABSTRACT FROM AUTHOR]

Direct insight into the elusive nature of multiple bonding between gallium atoms in molecular solids is obtained with ultrahigh ‐ field two ‐ dimensional 71Ga NMR spectroscopy. The gallium – gallium J couplings offer a novel perspective on the electronic structure of these bonds, and the intriguing results are discussed in the context of analogous data for carbon−carbon and boron−boron spin pairs. Cover designed by L. Kobera; background photograph courtesy of V. Terskikh. More information can be found in the Full Paper by D. L. Bryce et al. on page 9565 ff. [ABSTRACT FROM AUTHOR]

5–15% of cancer patients have unrelieved pain or undesirable side effects despite current best management. IDDS may give better pain control and fewer side effects but there are no randomized clinical trials (RCT). A RCT of IDDS plus CMM vs. CMM alone in patients with unrelieved pain (>5 on 0–10 scale) despite current best management is in progress. The IDDS is the SynchroMed Implantable Drug Delivery System. Outcomes include pain control, quality of life (Brief Pain Inventory, SF-12, Caregiver Quality of Life Survey), and toxicity (National Cancer Institute Common Toxicity Criteria), Health resource utilization data will assess if avoided pain therapy expenditures balance IDDS cost. The study can detect a 20% difference in pain control and toxicity with a target accrual of 200 patients. Over 100 patients have been accrued at 19 centers in 5 countries. The study arms are balanced with respect to pain intensity (VAS), life expectancy, demographic variables, source of cancer pain, and baseline opioid use vs. unacceptable opioid side effects. An interim analysis will present data on patient baseline characteristics; management course at different centers; and effect of therapy on pain scores, quality of life, toxicity, and resource utilization. [ABSTRACT FROM AUTHOR]

Review: 133 refs. [ABSTRACT FROM AUTHOR]