Ring current effects in crystals. Evidence from 13C chemical shift tensors for intermolecular shielding in 4,7-di-t-butylacenaphthene versus 4,7-di-t-butylacenaphthylene

13C chemical shift tensor data from 2D FIREMAT spectra are reported for 4,7-di-t-butylacenaphthene and 4,7-di-t-butylacenaphthylene. In addition, calculations of the chemical shielding tensors were completed at the B3LYP/6-311G** level of theory. While the experimental tensor data on 4,7-di-t-butylacenaphthylene are in agreement with theory and with previous data on polycyclic aromatic hydrocarbons, the experimental and theoretical data on 4,7-di-t-butylacenaphthene lack agreement. Instead, larger than usual differences are observed between the experimental chemical shift components and the chemical shielding tensor components calculated on a single molecule of 4,7-di-t-butylacenaphthene, with a root mean square (rms) error of +/-7.0 ppm. The greatest deviation is concentrated in the component perpendicular to the aromatic plane, with the largest value being a 23 ppm difference between experiment and theory for the 13CH2 carbon delta11 component. These differences are attributed to an intermolecular chemical shift that arises from the graphitelike, stacked arrangement of molecules found in the crystal structure of 4,7-di-t-butylacenaphthene. This conclusion is supported by a calculation on a trimer of molecules, which improves the agreement between experiment and theory for this component by 14 ppm and reduces the overall rms error between experiment and theory to 4.0 ppm. This intermolecular effect may be modeled with the use of nuclei independent chemical shieldings (NICS) calculations and is also observed in the isotropic 1H chemical shift of the CH2 protons as a 4.2 ppm difference between the solution value and the solid-state chemical shift measured via a 13C-1H heteronuclear correlation experiment.     

Intermolecular shielding from molecular magnetic susceptibility. A new view of intermolecular ring current effects

This paper presents calculations of the NICS (nuclear independent chemical shieldings) in a rectangular grid surrounding the molecules of benzene, naphthalene and coronene. Using the relationship between calculated NICS and the induced magnetic field, the calculated NICS are used to predict intermolecular effects due to molecular magnetic susceptibility or ring current effects. As expected from approximate ring current models, these intermolecular shielding effects are concentrated along the direction perpendicular to the molecular plane and they approach asymptotically to a dipolar functional dependence, i.e. (1-3 cos(2)theta)/r(3)). The deviations from the dipolar functional form require that the calculations of these intermolecular effects be done using a suitable interpolation scheme of the NICS calculated on the grid. The analysis of the NICS tensor components shows that these intermolecular shielding effects should be primarily expected on shielding components of the neighboring molecules nuclei, which are perpendicular to the molecular plane of the aromatic compound generating the induced field. The analysis of the calculated NICS along the series benzene, naphthalene and coronene shows that these intermolecular effects increase monotonically with the number of aromatic rings.     

Ion-binding study by 17O solid-state NMR spectroscopy in the model peptide Gly-Gly-Gly at 19.6 T

Li(+) and Ca(2+) binding to the carbonyl oxygen sites of a model peptide system has been studied by (17)O solid-state NMR spectroscopy. (17)O chemical shift (CS) and quadrupole coupling (QC) tensors are determined in four Gly-(Gly-(17)O)-Gly polymorphs by a combination of stationary and fast magic-angle spinning (MAS) methods at high magnetic field, 19.6 T. In the crystal lattice, the carbonyl oxygen of the central glycyl residue in two gly-gly-gly polymorphs form intermolecular hydrogen bonds with amides, whereas the corresponding carbonyl oxygens of the other two polymorphs form interactions with Li(+) and Ca(2+) ions. This permits a comparison of perturbations on (17)O NMR properties by ion binding and intermolecular hydrogen bonding. High quality spectra are augmented by density functional theory (DFT) calculations on large molecular clusters to gain additional theoretical insights and to aid in the spectral simulations. Ion binding significantly decreases the two (17)O chemical shift tensor components in the peptide plane, delta(11) and delta(22), and, thus, a substantial change in the isotropic chemical shift. In addition, quadrupole coupling constants are decreased by up to 1 MHz. The effects of ion binding are found to be almost an order of magnitude greater than those induced by hydrogen bonding.     

Elusive forms and structures of N-hydroxyphthalimide: the colorless and yellow crystal forms of N-hydroxyphthalimide

A comprehensive structural characterization of the colorless and yellow forms of N-hydroxyphthalimide (NHP), the deuterated form (NDP), and the ethoxylated form (ethoxy-NHP) has been carried out using single-crystal X-ray diffraction, FTIR and Raman spectroscopies, and scanning electron microscopy. Both NHP and NDP forms crystallize in the monoclinic space group (P21/c, No. 14). The various forms of NHP differ in the way in which the molecules adjoin one another through their N-hydroxyl groups and how the carbonyls of the isoindole-1,3-dione ring differ through intermolecular hydrogen bonding. Although the hydrogen bonding about the b axis is virtually the same, the isoindole-1,3-dione ring experiences different twists for the two NHP forms. Both the colorless and yellow forms of NHP exhibit strong intermolecular hydrogen bonding between O(3) and H(1). In the yellow form, the N-hydroxyl group is significantly out of the plane (approximately 1.19 degrees ), but the N-hydroxyl group in the colorless form is only approximately 0.06 degrees out of the plane. Both forms of NHP reveal an infinite chain of intermolecular hydrogen-bonded molecules in the direction of the b axis; however, the molecules are ordered differently within the unit cells. The hydrogen-bond geometry for the yellow form of NHP is O(2)-H(1)...O(3), with an angle of 185 degrees , intermolecular distances of O(2)...O(3) = 2.68 A and H(1)...O(3) = 1.70 A, and an intramolecular hydrogen bond of O(1)...H(1) = 1.17 A. The colorless form of NHP shows an intermolecular hydrogen-bond geometry between O(3) and H(1) with a distance of 1.78 A; the O(2)-O(3) distance is 2.71 A. The O(2)-H(1)...O(3) angle is 159 degrees, and the intramolecular distance is O(1)...H(1) = 0.97 A. The N-ethoxy derivative of NHP crystallizes in an orthorhombic space group (Pnma, No. 62) and exhibits no hydrogen bonding, displaying a strong head-to-tail stacking of the planar rings along the needle axis direction.     

13C NMR investigation of solid-state polymorphism in 10-deacetyl baccatin III

To investigate the origins of solid-state NMR shift differences in polymorphs, carbon NMR chemical shift tensors are measured for two forms of solid 10-deacetyl baccatin III: a dimethyl sulfoxide (DMSO) solvate and an unsolvated form. A comparison of ab initio computed tensors that includes and omits the DMSO molecules demonstrates that lattice interactions cannot fully account for the shift differences in the two forms. Instead, conformational differences in the cyclohexenyl, benzoyl, and acetyl moieties are postulated to create the differences observed. X-ray analysis of six baccatin III analogues supports the suggested changes in the cyclohexenyl and benzoyl systems. The close statistical match of the (13)C chemical shifts of both polymorphic forms with those calculated using the X-ray geometry of 10-deacetyl baccatin III supports the contention that the B, C, and D rings are fairly rigid. Therefore, the observed tensor differences appear to arise primarily from conformational variations in ring substituents and the cyclohexenyl ring.     

Application of solid-state 35Cl NMR to the structural characterization of hydrochloride pharmaceuticals and their polymorphs

Solid-state (35)Cl NMR (SSNMR) spectroscopy is shown to be a useful probe of structure and polymorphism in HCl pharmaceuticals, which constitute ca. 50% of known pharmaceutical salts. Chlorine NMR spectra, single-crystal and powder X-ray diffraction data, and complementary ab initio calculations are presented for a series of HCl local anesthetic (LA) pharmaceuticals and some of their polymorphs. (35)Cl MAS SSNMR spectra acquired at 21.1 T and spectra of stationary samples at 9.4 and 21.1 T allow for extraction of chlorine electric field gradient (EFG) and chemical shift (CS) parameters. The sensitivity of the (35)Cl EFG and CS tensors to subtle changes in the chlorine environments is reflected in the (35)Cl SSNMR powder patterns. The (35)Cl SSNMR spectra are shown to serve as a rapid fingerprint for identifying and distinguishing polymorphs, as well as a useful tool for structural interpretation. First principles calculations of (35)Cl EFG and CS tensor parameters are in good agreement with the experimental values. The sensitivity of the chlorine NMR interaction tensor parameters to the chlorine chemical environment and the potential for modeling these sites with ab initio calculations hold much promise for application to polymorph screening for a wide variety of HCl pharmaceuticals.     

Interplay of supramolecular organization, metallophilic interactions, phase changes, and luminescence in four polymorphs of IrI(CO)2(OC(CH3)CHC(CH3)N(p-tol))

Four polymorphs of IrI(CO)2(OC(CH3)CHC(CH3)N(p-tol)) have been characterized by single crystal X-ray crystallography. While all contain the same molecular unit with no significant structural variations within the molecules, all show different degrees of metallophilic interactions between the planar molecules. Three of these (the amber, the pale yellow, and the orange forms) are stable at room temperature, while the fourth, the L. T. orange form, is only obtained by cooling the orange polymorph. At 77 K, the amber, pale yellow, and L. T. orange polymorphs show intense luminescence. The variations in the luminescence among the polymorphs are considered in the context of the structural differences between them and the nature of the metallophilic interactions between the iridium centers. These results demonstrate how subtle variations in molecular organization can affect the physical properties of planar d8 transition metal compounds, which are an important class of lumiphores.     

Crystal structure of a methine dye, C.I. Disperse Blue 354.

Crystals of C.I. Disperse Blue 354, a commercial methine disperse dye, were grown from an ethyl acetate and the crystal structure was determined. Results show that two aromatic planes are effectively coplanar with the dihedral angle of 10.61(11) degrees. The dicyanomethylene group is slightly twisted and two n-hexyl groups tend to be separated with one alkyl group being at the level of the aromatic plane, and another one below it. The intermolecular hydrogen bonds and the interlayer pi-pi stacking stabilize the crystal packing.     

Factors governing the three-dimensional hydrogen-bond network structure of poly(m-phenylene isophthalamide) and a series of its model compounds (4): similarity in local conformation and packing structure between a complicated three-arm model compound and the linear model compounds

Crystal structure of a three-arm model compound of poly(m-phenylene isophthalamide) (PMIA), N,N',N' '-triphenyl trimesamide Phi(CONHPhi)(3), has been analyzed by the X-ray diffraction method. The torsional angles around the bonds connecting the amide group and the central benzene ring are 24-34 degrees , almost the same as those observed for many kinds of aromatic amide compounds, reflecting mainly the intramolecular energetic balance between the amide and benzene groups. On the other hand, the torsional angles around the bonds connecting the amide group and the outer benzene ring were found to distribute over a wide range of 2-51 degrees due to the additional effect of intermolecular interactions. This is the first example to show experimentally clearly the role of intra- and intermolecular interactions in the control of torsional angle around the benzene-amide linkage. The hydrogen bonds are formed between the amide groups of the neighboring molecules, resulting in the construction of three-dimensional network structure. The local packing structure of the three-arm compound was found to be essentially the same as those observed for PMIA and the linear model compounds, indicating a characteristic structural feature of the meta-linkage-type aromatic amide compounds. The energy calculation was made using the software Polymorph Predictor to extract the energetically most stable crystal structure, which was compared successfully with the X-ray analyzed structure.     

Calcium-43 chemical shift tensors as probes of calcium binding environments. Insight into the structure of the vaterite CaCO3 polymorph by 43Ca solid-state NMR spectroscopy

Natural-abundance (43)Ca 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 (43)Ca 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 (43)Ca 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 (43)Ca 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 P6(3)/mmc space group provides a better representation of the structure than does the orthorhombic Pbnm space group, thereby demonstrating the utility of (43)Ca solid-state NMR as a complementary tool to X-ray crystallographic methods.     

Polymorphism versus thermochromism: interrelation of color and conformation in overcrowded bistricyclic aromatic enes

The nature of the thermochromic form of overcrowded bistricyclic aromatic enes (BAEs) has been controversial for a century. We report the single-crystal X-ray structure analysis of the deep-purple and yellow polymorphs of 9-(2,7-dimethyl-9H-fluoren-9-ylidene)-9H-xanthene (11), which revealed the molecules in a twisted and a folded conformation, respectively. Therefore, the deeply colored thermochromic form B of BAEs is identified as having a twisted conformation and the ambient-temperature form A as having a folded conformation. This relationship between the color and the conformation is further supported by the X-ray structures of the deep-purple crystals of the twisted 9-(9H-fluoren-9-ylidene)-9H-xanthene (10), and of the yellow crystals of the folded 9-(11H-benzo[b]fluoren-11-ylidene)-9H-xanthene (12). Based on this conclusive crystallographic evidence, eleven previously proposed rationales of thermochromism in BAEs are refuted. In the twisted structures, the tricyclic moieties are nearly planar and the central double bond is elongated to 1.40 A and twisted by 42 degrees . In the folded structures, the xanthylidene moieties are folded by 45 degrees and the fluorenylidene moieties by 18-20 degrees . Factors stabilizing the twisted and folded conformations are discussed, including twisting of formal single or double bonds, intramolecular overcrowding, and the significance of a dipolar aromatic "xanthenylium-fluorenide" push-pull structure.     

Polymorphism of methyl 4‐amino‐3‐phenylisothiazole‐5‐carboxylate: an experimental and theoretical study

Being a close analogue of amflutizole, methyl 4‐amino‐3‐phenylisothiazole‐5‐carboxylate (C₁₁H₁₀N₂O₂S) was assumed to be capable of forming polymorphic structures. Noncentrosymmetric and centrosymmetric polymorphs have been obtained by crystallization from a series of more volatile solvents and from denser tetrachloromethane, respectively. Identical conformations of the molecule are found in both structures. The two polymorphs differ mainly in the intermolecular interactions formed by the amino group and in the type of stacking interactions between the π‐systems. The most effective method for revealing packing motifs in structures with intermolecular interactions of different types (hydrogen bonding, stacking, dispersion, etc.) is to study the pairwise interaction energies using quantum chemical calculations. Molecules form a column as the primary basic structural motif due to stacking interactions in both polymorphic structures under study. The character of a column (straight or zigzag) is determined by the orientations of the stacked molecules (in a `head‐to‐head' or `head‐to‐tail' manner). Columns bound by intermolecular N—H…O and N—H…N hydrogen bonds form a double column as the main structural motif in the noncentrosymmetric structure. Double columns in the noncentrosymmetric structure and columns in the centrosymmetric structure interact strongly within the ab crystallographic plane, forming a layer as a secondary basic structural motif. The noncentrosymmetric structure has a lower density and a lower (by 0.59 kJ mol^?1) lattice energy, calculated using periodic calculations, compared to the centrosymmetric structure.     

Relationship between the structure and enantioselectivity in the asymmetric reduction of 2,6-disubstituted acetophenones with DIP-Chloride. An ab initio study

Using computational and chemical studies, a relationship between the % ee achieved and the dihedral angles between the plane of the aromatic ring and the plane containing the carbonyl group has been established for asymmetric reductions with B-chlorodiisopinocampheylborane.     

Characterizing challenging microcrystalline solids with solid-state NMR shift tensor and synchrotron X-ray powder diffraction data: structural analysis of ambuic acid

Synchrotron X-ray powder diffraction and solid-state (13)C NMR shift tensor data are combined to provide a unique path to structure in microcrystalline organic solids. Analysis is demonstrated on ambuic acid powder, a widely occurring natural product, to provide the complete crystal structure. The NMR data verify phase purity, specify one molecule per asymmetric unit, and provide an initial structural model including relative stereochemistry and molecular conformation. A refinement of X-ray data from the initial model establishes that ambuic acid crystallizes in the P2(1) space group with unit cell parameters a = 15.5047(7), b = 4.3904(2), and c = 14.1933(4) A and beta = 110.3134(3) degrees . This combined analysis yields structural improvements at two dihedral angles over prior NMR predictions with differences of 103 degrees and 37 degrees found. Only minor differences of +/-5.5 degrees , on average, are observed at all remaining dihedral angles. Predicted hydroxyl hydrogen-bonding orientations also fit NMR predictions within +/-6.9 degrees . This refinement corrects chemical shift assignments at two carbons and reduces the NMR error by approximately 16%. This work demonstrates that the combination of long-range order information from synchrotron powder diffraction data together with the accurate shorter range structure given by solid-state NMR measurements is a powerful tool for studying challenging organic solids.     

Modeling the interplay of inter- and intramolecular hydrogen bonding in conformational polymorphs

The predicted stability differences of the conformational polymorphs of oxalyl dihydrazide and ortho-acetamidobenzamide are unrealistically large when the modeling of intermolecular energies is solely based on the isolated-molecule charge density, neglecting charge density polarization. Ab initio calculated crystal electron densities showed qualitative differences depending on the spatial arrangement of molecules in the lattice with the greatest variations observed for polymorphs that differ in the extent of inter- and intramolecular hydrogen bonding. We show that accounting for induction dramatically alters the calculated stability order of the polymorphs and reduces their predicted stability differences to be in better agreement with experiment. Given the challenges in modeling conformational polymorphs with marked differences in hydrogen bonding geometries, we performed an extensive periodic density functional study with a range of exchange-correlation functionals using both atomic and plane wave basis sets. Although such electronic structure methods model the electrostatic and polarization contributions well, the underestimation of dispersion interactions by current exchange-correlation functionals limits their applicability. The use of an empirical dispersion-corrected density functional method consistently reduces the structural deviations between the experimental and energy minimized crystal structures and achieves plausible stability differences. Thus, we have established which types of models may give worthwhile relative energies for crystal structures and other condensed phases of flexible molecules with intra- and intermolecular hydrogen bonding capabilities, advancing the possibility of simulation studies on polymorphic pharmaceuticals.     

Hydrogen bonding between phenols and fatty acid esters: (1)H NMR study and ab initio calculations

[structure: see text] (1)H NMR measurements and ab initio calculations were used to study the interactions between hindered/nonhindered phenols and carboxylic acid esters. The dihedral angle (phi) between the OH group and a plane of the aromatic ring is close to 0 degrees in the hydrogen-bonded nonhindered phenols, whereas for 2,6-di-tert-butyl-4-methylphenol the OH group is completely twisted out of the aromatic plane (phi approximately 90 degrees ).     

Color Polymorphism: Understanding the Diverse Solid‐State Packing and Color in Dimethyl‐3,6‐dichloro‐2,5‐dihydroxyterephthalate

Dimethyl‐3,6‐dichloro‐2,5‐dihydroxyterephthalate (MCHT) is known to exist in three differently packed crystals having three different colors, namely yellow (Y), light yellow (LY), and white (W). Apart from the difference in their color, the molecules in the crystals also differ in their intramolecular O?H???O and O?H???Cl hydrogen bonds. Time‐dependent DFT calculations reveal the role of the various types of hydrogen bonds in controlling the color of the polymorphs. Mechanistic pathways that lead to such transformations in the crystal are elucidated by solid‐state dispersion‐corrected DFT studies. Relative stabilities of the various polymorphs rationalize the experimentally observed transformations between them. Calculations reveal that the minimum‐energy pathway for the conversion of the Y form to a W form is through stepwise disrotatory motion of the two ?OH groups through a hybrid intermediate having one intramolecular O?H???O and one O?H???Cl bond. The LY form is shown to exist on the higher‐energy pathway involving a concerted Y→W transformation.     

Molecular and Crystal Structure of a Superstable Free Radical, 1,3-Diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl

The molecular and crystal structure of a superstable free radical, 1,3-diphenyl-1,4-dihydro-1,2,4-benzotriazin-4-yl, was studied by single crystal X-ray diffraction. The dihedral angle formed by the N-phenyl ring with the heteroring is considerably larger than that formed by the C-phenyl ring; two geminal C-N bonds in the dihydrotriazine ring have virtually equal length. In the crystal, the radical molecules form stacks along the 0b axis due to - interactions of the aromatic fragments of the molecules. The total effect of intermolecular contacts in the crystal leads to formation of a lamellar supramolecular structure.     

Two polymorphs of 2,5‐dichloro‐3,6‐bis(dibenzylamino)‐p‐hydroquinone with flexible dibenzylamino groups

We obtained two conformational polymorphs of 2,5‐dichloro‐3,6‐bis(dibenzylamino)‐p‐hydroquinone, C₃₄H₃₀Cl₂N₂O₂. Both polymorphs have an inversion centre at the centre of the hydroquinone ring (Z′ = ), and there are no significant differences between their bond lengths and angles. The most significant structural difference in the molecular conformations was found in the rotation of the phenyl rings of the two crystallographically independent benzyl groups. The crystal structures of the polymorphs were distinguishable with respect to the arrangement of the hydroquinone rings and the packing motif of the phenyl rings that form part of the benzyl groups. The phenyl groups of one polymorph are arranged in a face‐to‐edge motif between adjacent molecules, with intermolecular C—H…π interactions, whereas the phenyl rings in the other polymorph form a lamellar stacking pattern with no significant intermolecular interactions. We suggest that this partial conformational difference in the molecular structures leads to the significant structural differences observed in their molecular arrangements.     

13C and (15)N chemical shift tensors in adenosine,guanosine dihydrate, 2'-deoxythymidine,and cytidine

The (13)C and (15)N chemical shift tensor principal values for adenosine, guanosine dihydrate, 2'-deoxythymidine, and cytidine are measured on natural abundance samples. Additionally, the (13)C and (15)N chemical shielding tensor principal values in these four nucleosides are calculated utilizing various theoretical approaches. Embedded ion method (EIM) calculations improve significantly the precision with which the experimental principal values are reproduced over calculations on the corresponding isolated molecules with proton-optimized geometries. The (13)C and (15)N chemical shift tensor orientations are reliably assigned in the molecular frames of the nucleosides based upon chemical shielding tensor calculations employing the EIM. The differences between principal values obtained in EIM calculations and in calculations on isolated molecules with proton positions optimized inside a point charge array are used to estimate the contributions to chemical shielding arising from intermolecular interactions. Moreover, the (13)C and (15)N chemical shift tensor orientations and principal values correlate with the molecular structure and the crystallographic environment for the nucleosides and agree with data obtained previously for related compounds. The effects of variations in certain EIM parameters on the accuracy of the shielding tensor calculations are investigated.