Boris A. Zakharov

A high‐pressure single‐crystal to single‐crystal phase transition in DL‐alaninium semi‐oxalate monohydrate with switching‐over hydrogen bonds

A single-crystal to single-crystal transition in DL-alaninium semi-oxalate monohydrate at a pressure between 1.5 and 2.4 GPa was studied by single-crystal X-ray diffraction and Raman spectroscopy. This is the first example of a single-crystal diffraction study of a high-pressure phase transition in a crystalline amino acid salt hydrate. Selected hydrogen bonds switch over and become bifurcated, whereas the others are compressed continuously. The transition is accompanied by pronounced discontinuities in the cell parameters and volume versus pressure, although no radical changes in the molecular packing are induced. Although, in contrast to DL-alanine, in the crystal structure of the salt there are short O-H···O hydrogen bonds, the structure of the salt is more compressible. At the same time, the structure of DL-alanine does not undergo pressure-induced phase transitions, whereas the structure of DL-alaninium semi-oxalate monohydrate does, and at a relatively low pressure. The anisotropy of lattice strain for the low-pressure phase differs from that on cooling at ambient pressure; interestingly, the anisotropy of the pressure-induced compression of the high-pressure phase is quite similar to the lattice strain of the low-pressure phase on cooling.

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.

Effect of pressure on crystalline L- and DL-serine: revisited by a combined single-crystal X-ray diffraction at a laboratory source and polarized Raman spectroscopy study.

Information on the effect of pressure on hydrogen bonds, which could be derived from single-crystal X-ray diffraction at a laboratory source and polarized Raman spectroscopy, has been compared. L-Serine and DL-serine were selected for this case study. The role of hydrogen bonds in pressure-induced phase transitions in the first system and in the structural stability of the second one are discussed. Non-monotonic distortion of selected hydrogen bonds in the pressure range below ~1-2 GPa, a change in the compression mechanism at ~2-3 GPa, and the evidence of formation of bifurcated N-H...O hydrogen bonds in DL-serine at ~3-4 GPa are considered.

β-Alanine under pressure: towards understanding the nature of phase transitions

We report the unusual behavior of β-alanine under pressure. Depending on the protocol with which pressure was increased, the crystals of β-alanine I after transition to phase II either transformed into monoclinic phase V at approximately 6 GPa or remained orthorhombic at least up to 8 GPa in phase II with a molecular packing very similar to that of phase I.

Polymorphism of “glycine–glutaric acid” co-crystals: the same phase at low temperatures and high pressures

Glycine–glutaric acid co-crystals undergo a first-order reversible phase transition at a very low pressure (0.1 GPa) to give the low-temperature phase described recently. This fact was confirmed by single crystal X-ray diffraction and Raman spectroscopy.

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.

Glycinium semi-malonate and a glutaric acid–glycine cocrystal: new structures with short O—H...O hydrogen bonds

Glycinium semi-malonate, C(2)H(6)NO(2)(+)·C(3)H(3)O(4)(-), (I), and glutaric acid-glycine (1/1), C(2)H(5)NO(2)·C(5)H(8)O(4), (II), are new examples of two-component crystal structures containing glycine and carboxylic acids. (II) is the first example of a glycine cocrystal which cannot be classified as a salt, as glutaric acid remains completely protonated. In the structure of (I), there are chains formed exclusively by glycinium cations, or exclusively by malonate anions, and these chains are linked with each other. Two types of very short O-H...O hydrogen bonds are present in the structure of (I), one linking glycinium cations with malonate anions, and the other linking malonate anions with each other. In contrast to (I), no direct linkages between molecules of the same type can be found in (II); all the hydrogen-bonded chains are heteromolecular, with molecules of neutral glutaric acid alternating with glycine zwitterions, linked by two types of short O-H...O hydrogen bonds.

A single-crystal to single-crystal phase transition in [Co(NH3)5NO2]Br2 at high pressure: a step towards understanding linkage photo-isomerisation

Changes in the crystal structure of [Co(NH3)5NO2]Br2 – including a previously unknown single-crystal to single-crystal phase transition above 6.0 GPa – were followed from ambient pressure to 6.9 GPa and discussed in relation to the structural mechanism of homogeneous linkage photoisomerisation that is accompanied by photomechanical effects in the same compound.

Synthesis and structure-activity relationship of novel 1,4-diazabicyclo[2.2.2]octane derivatives as potent antimicrobial agents.

A series of new quaternary 1,4-diazabicyclo[2.2.2]octane derivatives was synthesized and evaluated for activity against several strains of both Gram positive and Gram negative bacteria and one strain of fungus under different inoculum size. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six species of microorganisms were tested. Results show a clear structure-activity relationship between alkyl chain length of substitutions of 1,4-diazabicyclo[2.2.2]octane tertiary amine sites and antimicrobial activity. In the case of compounds 4a-4k, MIC was found to decrease with the increase of the alkyl chain length from ethyl to dodecyl and then to increase at higher chain length (nxa0>xa014). The MIC values were found to be low for the compounds 4f and 4g with alkyl chains ranging from 10 to 12 carbons in length (1.6xa0μg/ml) and were comparable to the reference drug Ciprofloxacin. Also, time-kill assay was performed to examine the bactericidal kinetics. Results indicated that 4f and 4g had rapid killing effects against Staphylococcus aureus, and eliminated 100% of the initial inoculum of bacteria in 2.5xa0h at the concentration of 10xa0μg/ml. In addition, compound 4g eliminate more than 99.9% of the initial inoculum of Ps. aeruginosa after 2.5xa0h of interaction but the activity of compound 4f against this species seems to be weak. Thus, 4g had strong bactericidal activity and could rapidly kill Gram positive S.xa0aureus, as well as Gram negative Ps. aeruginosa at low and high inoculum size.

Polymorphic transformations in glycine co-crystals at low temperature and high pressure: two new examples as a follow-up to a glycine–glutaric acid study

The effects of temperature and pressure on the co-crystals of glycine with DL-tartaric and phthalic acids (GTa and GPh, respectively) have been studied by X-ray diffraction and Raman spectroscopy in comparison with those on glycine–glutaric acid (GGa). On cooling, no phase transitions were observed in GTa or GPh, in contrast to the situation with GGa. On hydrostatic compression, both GTa and GPh underwent reversible phase transformations, accompanied by fracture. In the high-pressure phases, the main structural framework was preserved, and the number of crystallographically independent molecules in the unit cell increased. In GTa, dimers are squeezed together so that some hydrogen bonds get a three-centered character, and the interactions of one of the two glycine molecules change dramatically.