Valeri A. Drebushchak

Synthesis and calorimetric investigation of unstable β-glycine

Abstract A new procedure for the synthesis of the unstable β -polymorph of glycine has been developed. The amount of the sample synthesized in one run is enough to carry out the calorimetric measurements. The transformation of β -glycine into α -glycine on heating was investigated. The transformation starts at 340xa0K as an exothermic process and takes some time for the completion. This agrees with the recent results of X-ray single crystal investigations showing that the β–α transformation is the recrystallization.

Solid-state transformations in the β-form of chlorpropamide on cooling to 100 K

A single-crystal X-ray diffraction study of the effect of cooling down to 100 K on the β-form of chlorpropamide, 4-chloro-N-(propylaminocarbonyl)benzenesulfonamide, has revealed reversible phase transitions at ∼257 K and between 150 and 125 K: β (Pbcn, Z = 1) ⇔ β(II) (P2/c, Z = 2) ⇔ β(III) (P2/n, a = 2a, Z = 4); the sequence corresponds to cooling. Despite changes in the space group and number of symmetry-independent molecules, the volume per molecule changes continuously in the temperature range 100-300 K. The phase transition at ∼257 K is accompanied by non-merohedral twinning, which is preserved on further cooling and through the second phase transition, but the original single crystal does not crack. DSC (differential scanning calorimetry) and X-ray powder diffraction investigations confirm the phase transitions. Twinning disappears on heating as the reverse transformations take place. The second phase transition is related to a change in conformation of the alkyl tail from trans to gauche in 1/4 of the molecules, regularly distributed in the space. Possible reasons for the increase in Z upon cooling are discussed in comparison to other reported examples of processes (crystallization, phase transitions) in which organic crystals with Z > 1 have been formed. Implications for pharmaceutical applications are discussed.

Low-temperature phase transition in glycine-glutaric acid co-crystals studied by single-crystal X-ray diffraction, Raman spectroscopy and differential scanning calorimetry.

The occurrence of a first-order reversible phase transition in glycine-glutaric acid co-crystals at 220-230 K has been confirmed by three different techniques - single-crystal X-ray diffraction, polarized Raman spectroscopy and differential scanning calorimetry. The most interesting feature of this phase transition is that every second glutaric acid molecule changes its conformation, and this fact results in the space-group symmetry change from P2(1)/c to P1. The topology of the hydrogen-bonded motifs remains almost the same and hydrogen bonds do not switch to other atoms, although the hydrogen bond lengths do change and some of the bonds become inequivalent.

Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study.

In the present case study of tolazamide we illustrate how many seemingly contradictory results that have been obtained from experimental observations and theoretical calculations can finally start forming a consistent picture: a puzzle put together. For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique among the large family of sulfonylureas, which was known to be significantly more prone to polymorphism than many other organic compounds. The present work employs a broad and in-depth analysis that includes the use of optical microscopy, single-crystal and powder X-ray diffraction, IR and Raman spectroscopies, DSC, semiempirical PIXEL calculations and DFT of three polymorphs of tolazamide. This case study shows how the polymorphs of a molecular crystal can be overlooked even if discovered serendipitously on one of numerous crystallizations, and how very different molecular packings can be practically isoenergetic but still crystallize quite selectively and transform one into another irreversibly upon heating.

Low-temperature heat capacity of pentlandite

Abstract The heat capacity of synthetic pentlandite Fe4.60Ni4.54S8 was measured over the temperature range 6-306 K. Experimental values of CP (T) indicate that there are no phase transitions. The thermodynamic functions CP (T), H(T) - H(0), and S(T) - S(0) were evaluated: CP (298.15) = 442.7 J/mol·K, S(298.15) - S(0) = 474.9 J/mol·K, and H(298.15) - H(0) = 76280 J/mol (molar mass: 779.877 g). Below 10 K, the heat capacity of pentlandite fits the regression CP(T) = a T + b T3. The linear term is typical of metals and known as an electronic contribution to the heat capacity. This agrees with the hypothesis that there is metal bonding among cations in tetrahedral sites.

Polymorphism of chlorpropamide: structure and transitions

2,2’:6’,2’’-Terpyridine (tpy), which is practically non-fluorescent (Φ <0.01) in organic solutions, in an amorphous solid and a needle crystal (P212121, Z=4), was found to show an efficient solid-state luminescence (365 nm, Φ =0.2) upon formation of a plate crystal (P21/c, Z=8). Furthermore, effective on-off switching of this solidstate luminescence was realized by heat-mode interconversion between the plate and needle crystals. It was shown that the rate constant of the non-radiative relaxation of the needle crystal (k=1.2x10s) was an order of magnitude larger than the plate crystal, while that of the emissive process were comparable (k~10s). In contrast to a frozen solution, both polymorphs did not exhibit phosphorescence at 77 K, suggesting that the triplet state might not be involved in the non-radiative process . Compar ing both polymorphs, tpy molecules were in different conformation, conrotated and disrotated, which migh t be due to a different molecular packing. Relation between the difference in the crystal structure and the solid-state luminescence property was further studied.

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.

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

Cation distribution in MgFe2O4 vs. pressure and temperature: Experiments in a “piston-cylinder” apparatus

Abstract The cation distribution in magnesioferrite MgFe2O4 was investigated using a “piston-cylinder” apparatus at three pressures (ambient, 1, and 2 GPa) over a temperature range of 600 to 1200 °C. Quenched samples of magnesioferrite were investigated by X-ray powder diffraction. The inversion parameter was derived from the unit-cell parameter at ambient temperature. The inversion parameter increases with pressure, being a smooth function of P-T conditions.The changes in the cation distribution in magnesioferrite caused by the changes in P-T conditions produce the contributions to the bulk modulus (<0.01%) and thermal expansion coefficient (12.60%). On average, the pressure increment of 0.01 GPa is compensated for by 1 °C heating. The effect of pressure on the cation ordering obeys the fundamental relationship (dV/dx)T,P (dx/dP)T < 0. The terms are (dV/dx) < 0 and (dx/dP) > 0 for MgFe2O4 and MgAl2O4.