Vasily S. Minkov

L-cysteinium semioxalate.

The title salt, C3H8NO2+.C2HO4-, formed between L-cysteine and oxalic acid, was studied as part of a comparison of the structures and properties of pure amino acids and their cocrystals. The structure of the title salt is very different from that formed by oxalic acid and equivalent amounts of D- and L-cysteine molecules. The asymmetric unit contains an L-cysteinium cation and a semioxalate anion. The oxalate anion is only singly deprotonated, in contrast with the double deprotonation in the crystal structure of bis(DL-cysteinium) oxalate. The oxalate anion is not planar. The conformation of the L-cysteinium cation differs from that of the neutral cysteine zwitterion in the monoclinic and orthorhombic polymorphs of L-cysteine, but is similar to that of the cysteinium cation in bis(DL-cysteinium) oxalate. The structure of the title salt can be described as a three-dimensional framework formed by ions linked by strong O-H...O and N-H...O and weak S-H...O hydrogen bonds, with channels running along the crystallographic a axis containing the bulky -CH2SH side chains of the cysteinium cations. The cations are only linked through hydrogen bonds via semioxalate anions. There are no direct cation-cation interactions via N-H...O hydrogen bonds between the ammonium and carboxylate groups, or via weaker S-H...S or S-H...O hydrogen bonds.

Dynamics and Thermodynamics of Crystalline Polymorphs. 2. β-Glycine, Analysis of Variable-Temperature Atomic Displacement Parameters

Multitemperature synchrotron diffraction data to 0.5 Å resolution in the temperature range 10-298 K and neutron data at 18 K of the α-glycine polymorph have been collected at the KEK photon factory (PF), SPring-8 and the Institut Laue Langevin (ILL) for the study of molecular motion in the crystal and of the associated thermodynamic functions. Atomic displacement parameters (ADPs) of non-H atoms are obtained from refinements based on nonspherical atomic scattering factors (invariom model) to minimize correlation between parameters describing thermal motion and valence electron density. The ADPs in the temperature range 50-298 K from SPring-8 connect smoothly with those from neutron diffraction at 18 K and 288-323 K. The combined ADPs from both sources covering the temperature range 18-323 K are used for a normal-mode analysis in the molecular mean field approximation. The lattice vibration frequencies from the ADP analysis and the internal vibration frequencies from an ONIOM (B3LYP/6-311+G(2d,p):PM3) calculation together with the Einstein, Debye, and Nernst-Lindemann models of heat capacity are used to calculate Cp, Hvib, and Svib values that are in good agreement with those from calorimetry.

Contribution of weak S-H · · · O hydrogen bonds to the side chain motions in D,L-homocysteine on cooling.

Sulfhydryl groups play an important role in the formation of native structures of proteins and their biological functions. In the present work, we report for the first time the crystal structure of D,L-homocysteine and the results of a detailed study of the dynamics of its sulfhydryl group on cooling by precise single-crystal X-ray diffraction combined with polarized Raman spectroscopy of oriented single crystals. Although the crystal structures of both D,L-cysteine and D,L-homocysteine are layered, hydrogen bonds formed by -SH groups differ. In contrast with the crystal structure of D,L-cysteine with weak S-H · · · S hydrogen bonds between layers, D,L-homocysteine resembles the structures of amino acids with hydrophobic aliphatic side chains with no hydrogen bonds between the layers. The side chain of D,L-homocysteine forms a three-centered S-H · · · O hydrogen bond with carboxylate groups of two neighboring zwitterions. On cooling down, despite the shortening of the two S · · · O distances in the bifurcated S-H · · · O hydrogen bond, the wavenumber of the stretching vibrations of -SH groups increases. The same effect was also observed previously for other sulfhydryl containing amino acids, L-cysteine, and N-acetyl-L-cysteine on increasing pressure and is related to the strengthening of a three-centered bifurcated S-H · · · O hydrogen bond.

High-pressure crystallography of periodic and aperiodic crystals

This article discusses the high-pressure behaviour of molecular crystal structures, energetic materials, phases relevant to the Earth’s interior, materials with a pressure-induced expansion in one or two directions, dealing with high-pressure data from crystals with twinning and pseudosymmetry, pressure-induced phase transitions including an incommensurate phase, and technical developments.

Betaine 0.77-perhydrate 0.23-hydrate and common structural motifs in crystals of amino acid perhydrates

The title compound, betaine 0.77-perhydrate 0.23-hydrate, (CH3)3N(+)CH2COO(-)·0.77H2O2·0.23H2O, crystallizes in the orthorhombic noncentrosymmetric space group Pca2(1). Chiral molecules of hydrogen peroxide are positionally disordered with water molecules in a ratio of 0.77:0.23. Betaine, 2-(trimethylazaniumyl)acetate, preserves its zwitterionic state, with a positively charged ammonium group and a negatively charged carboxylate group. The molecular conformation of betaine here differs from the conformations of both anhydrous betaine and its hydrate, mainly in the orientation of the carboxylate group with respect to the C-C-N skeleton. Hydrogen peroxide is linked via two hydrogen bonds to carboxylate groups, forming infinite chains along the crystallographic a axis, which are very similar to those in the crystal structure of betaine hydrate. The present work contributes to the understanding of the structure-forming factors for amino acid perhydrates, which are presently attracting much attention. A correlation is suggested between the ratio of amino acid zwitterions and hydrogen peroxide in the unit cell and the structural motifs present in the crystal structures of all currently known amino acids perhydrates. This can help to classify the crystal structures of amino acid perhydrates and to design new crystal structures.

Furosemide solvates: can they serve as precursors to different polymorphs?

The importance of polymorphism of molecular crystals is hard to overestimate, especially when dealing with compounds used as materials or drugs. Different polymorphs of a drug substance may have different properties related to their manufacturing, therapeutic usage, or storage (density, hygroscopicity, melting points, thermal stability, solubility, rate of dissolution, surface free energy, toxicity, bioavailability, tabletting, etc.). Different polymorphs, solvates, and co-crystals can be patented, and this opens the way for a competition with brand drugs. Since the energies of different polymorphs are sometimes very close, producing desirable crystalline forms is quite a challenge and can also be complicated by the phenomena of concomitant polymorphism (when several polymorphs crystallize simultaneously from the same batch), or erratic and poorly reproducible (when crystallization gives different polymorphs even at seemingly identical experimental conditions). The aim of the present study was to crystallize various solvates of furosemide, to check whether these solvates can be used as precursors for producing different polymorphs of pure furosemide on their subsequent decomposition upon heating, and to search any correlation between the crystal structures of the solvates and on the furosemide polymorphs produced by desolvation. Four solvates of furosemide with tetrahydrofuran, dioxane, dimethylformamide, and dimethylsulfoxide were crystallized. The detailed structural analysis of furosemide-containing crystal structures showed that the molecule of furosemide has a high conformational lability because of the rotations of the sulfamoyl and furanylmethylamino fragments. Some of the furosemide conformations were shown to be stabilized by the intramolecular N−H•••Cl H-bond. Desolvation of the four solvates was studied by TG and X-ray diffraction and was shown to give different products depending on the precursor and particle size.

Formation of bifurcated S—H...O hydrogen bonds in cysteine-containing crystal structures on increasing pressure

In a series of recent publications, the crystals of L-and DL-cysteine were shown to undergo multiple phase transitions upon variation of temperature and pressure. All these transitions are related to rotation of the amino acid side chain accompanied by switching the weak S-H...X hydrogen bonds. Accordingly, cysteinecontaining crystal structures should be stabilized with respect to phase transitions by measures that reduce the mobility of the side chain in the crystalline environment. In the recent work, we show that this can be achieved by increasing the significance of the side chain –SH group as a participant in intermolecular hydrogen bonds, either by N-acetylation, which removes the strong –NH+3 donor of cysteine and leaves a system without strong charge-assisted interactions, or by co-crystallization with an acid (oxalic acid) that converts the amino acid to a cation and itself forms a strong anion H-bond acceptor, thus boosting the importance of potential –SH donors. The crystal structures of the three compounds N-acetyl-L-cysteine, DLcysteinium semioxalate, and bis(DL-cysteinium) oxalate have thus been studied with variation of temperature and pressure. Cooling down to 4 K and increasing pressure up to 9.5 GPa did not result in any structural phase transitions in N-acetyl-L-cysteine and bis(DLcysteinium) oxalate. In case of DL-cysteinium semioxalate, increasing pressure caused a phase transition at a much higher pressure (~6 GPa), compared to the ranges of pressure-induced phase transitions observed earlier for both monoclinic and orthorhombic L-cysteine (2.5–3.9 GPa and 1.1–2.5 GPa, respectively) or DL-cysteine (0.1–5 GPa). This phase transition had a large hysteresis, so that the reverse transformation on decompression was observed at ~3.7 GPa only, and was accompanied by a change in molecular conformations, as well as by the reorganization in the N–H... O hydrogen bonds in the crystal structure. The precise polarized Raman spectroscopy from oriented single crystals and single crystal X-ray diffraction study of N-acetyl-L cysteine reveals continuous changes in S-H...O hydrogen bond on increasing pressure resulting in formation of bifurcated S H...O hydrogen bond where oxygens from carbonyl and carboxyl groups act as acceptors. The blue shift of stretching vibrations of -SH group in orthorhombic and monoclinic L-cysteine on increasing pressure at the shortening of S...O distance may be explained by formation of the bifurcated hydrogen bonds in crystal structures. The work was partly supported by Integration Project of SB RAS No. 108 and the Ministry of Education and Science of the Russian Federation (agreement No. 14.B37.21.1093).

Effect of high pressure/low temperature on cysteine, its salts and derivatives

Effect of high-pressure / low temperature on cysteine, its salts and derivatives Vasily S. Minkov,a,b Boris A. Kolesov,a,c Sergey V. Goryainov,a,d Valery A. Drebushchak,a,d Tatyana N. Drebushchak,a,b Andrey G. Ogienko,a,c Elena V. Boldyreva,a,b aREC-008 Novosibirsk State University (Russian Federation). bInstitute of Solid State Chemistry and Mechanochemistry SB RAS (Russian Federation). cInstitute of Inorganic Chemistry SB RAS (Russian Federation). dInstitute of Geology and Mineralogy SB RAS Novosibirsk, (Russian Federation). E-mail: vasilyminkov@yahoo.com