Synthesis, antiviral activity, preliminary pharmacokinetics and structural parameters of thiazolide amine salts

Background: The thiazolides, typified by nitazoxanide, are an important class of anti-infective agents. A significant problem with nitazoxanide and its active circulating metabolite tizoxanide is their poor solubility. Results: We report the preparation and evaluation of a series of amine salts of tizoxanide and the corresponding 5-Cl thiazolide. These salts demonstrated improved aqueous solubility and absorption, as shown by physicochemical and in vivo measurements. They combine antiviral activity against influenza A virus with excellent cell safety indices. We also report the x-ray crystal structural data of the ethanolamine salt. Conclusion: The ethanol salt of thiazolide retains the activity of the parent together with an improved cell safety index, making it a good candidate for further evaluation.

Erdmann’s Anion—An Inexpensive and Useful Species for the Crystallization of Illicit Drugs after Street Confiscations

Erdmann’s anion [1,6-diammino tetranitrocobaltate(III)] is useful in the isolation and crystallization of recently confiscated street drugs needing to be identified and catalogued. The protonated form of such drugs forms excellent crystals with that anion; moreover, Erdmann’s salts are considerably less expensive than the classically used AuCl4− anion to isolate them, while preparation of high-quality crystals is equally easy in both cases. We describe the preparation and structures of the K+CoH6N6O8− and NH4+CoH6N7O8−, salts of Erdmann’s. In addition, herein are described the preparations of this anion’s salts with cocaine (C17H28CoN7O12), with methamphetamine (C10H22CoN7O8), and with methylone (C22H34CoN8O14), whose preparation and stereochemistry had been characterized by the old AuCl4− salts methodology. For all species in this report, the space groups and cell constants were determined at 296 and 100 K, looking for possible thermally induced polymorphism—none was found. Since the structures were essentially identical at the two temperatures studied, we discuss only the 100 K results. Complete spheres of data accessible to a Bruker ApexII diffractometer with Cu–Kα radiation, λ = 1.54178 Å, were recorded and used in the refinements. Using the refined single crystal structural data for the street drugs, we computed their X-ray powder diffraction patterns, which are beneficial as quick identification standards in law enforcement work.

Structural analysis of β-glucosidase mutants derived from a hyperthermophilic tetrameric structure

β-Glucosidase fromPyrococcus furiosus(BGLPf) is a hyperthermophilic tetrameric enzyme which can degrade cellooligosaccharides to glucose under hyperthermophilic conditions and thus holds promise for the saccharification of lignocellulosic biomass at high temperature. Prior to the production of large amounts of this enzyme, detailed information regarding the oligomeric structure of the enzyme is required. Several crystals of BGLPf have been prepared over the past ten years, but its crystal structure had not been solved until recently. In 2011, the first crystal structure of BGLPf was solved and a model was constructed at somewhat low resolution (2.35 Å). In order to obtain more detailed structural data on BGLPf, the relationship between its tetrameric structure and the quality of the crystal was re-examined. A dimeric form of BGLPf was constructed and its crystal structure was solved at a resolution of 1.70 Å using protein-engineering methods. Furthermore, using the high-resolution crystal structural data for the dimeric form, a monomeric form of BGLPf was constructed which retained the intrinsic activity of the tetrameric form. The thermostability of BGLPf is affected by its oligomeric structure. Here, the biophysical and biochemical properties of engineered dimeric and monomeric BGLPfs are reported, which are promising prototype models to apply to the saccharification reaction. Furthermore, details regarding the oligomeric structures of BGLPf and the reasons why the mutations yielded improved crystal structures are discussed.

Thallium(I) complexes of fluorinated bis- and tris(pyrazolyl)borate ligands: [H2B{3,5-(CF3)2pz}2]Tl and [HB{3,5-(CF3)2pz}3]Tl

X-ray crystal structural data at 100 (2) K for the thallium(I) complex of a fluorinated bis(pyrazolyl)borate, {bis[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl-κN2]borato}thallium(I), [Tl(C10H4BF12N4)], abbreviated as [H2B{3,5-(CF3)2pz}2]Tl, and the related tris(pyrazolyl)borate, {tris[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl-κN2]borato}thallium(I), [Tl(C15H4BF18N6)], abbreviated as [HB{3,5-(CF3)2pz}3]Tl, are reported. [H2B{3,5-(CF3)2pz}2]Tl features a two-coordinate TlIatom with a bent geometry and a boat-shaped bis(pyrazolyl)borate ligand. It also has several additional inter- and intramolecular Tl...H and Tl...F contacts in the solid state. The tris(pyrazolyl)borate analogue [HB{3,5-(CF3)2pz}3]Tl has a trigonal–pyramidal thallium centre and features inter- and intramolecular Tl...F contacts.

THEORETICAL STUDIES ON THE EPR g FACTORS FOR Dy3+ IN YBa2Cu3O6

In the past years, the typical high Tc superconductor YBa 2 Cu 3 O 6 has been extensively studied by many authors. And electron paramagnetic resonance (EPR) studies of rare-earth ( Re 3+) ions in high- Tc oxide superconductors have attracted much interest because they can provide valuable information on spin-lattice relaxation, exchange interactions and the ground state properties of Re 3+ ions, which are further employed as sensitive probes of spin dynamics in high- Tc superconductor. The EPR anisotropic g factors of Dy 3+ in YBa 2 Cu 3 O 6 crystal has been measured by M.R. Gafurov et al., and there is no theoretical explanations related to the crystal structural data. In this paper, parameters g factors for Dy 3+ in YBa 2 Cu 3 O 6 are theoretically studied from the perturbation formulas of these parameters for a 4f9 ion in tetragonal symmetry. In these formulas, the contributions to the EPR parameters from the second-order perturbation terms and the admixtures of various excited states are taken into account. The related crystal-field parameters are determined from the superposition model and crystal structural data. The theoretical results show reasonable agreement with the experimental values.

The application of cluster analysis to identify conformational preferences in enones and enimines from crystal structural data

Cluster analysis can be an effective tool for analysing large quantities of data. Here it has been applied to the conformational analysis of enones and enimines in the crystalline solid state, using structural information mined from the Cambridge Structural Database. The forms that are common in the gaseous state and in solution are already known from spectroscopic studies. These forms are also found to be the most common conformations observed in the solid state; however, the clustering method highlights those structures that do not conform to the expected geometries. The study is supported by ab initio gas phase calculations on simple enone and enimine fragments.

Dovyrenite Ca6Zr[Si2O7]2(OH)4 - A New Mineral from Skarned Carbonate Xenoliths in Basic-Ultrabasic Rocks of the Ioko-Dovyren Massif, Northern Baikal Region, Russia

Dovyrenite Ca6Zr[Si2O7]2(OH)4 - A New Mineral from Skarned Carbonate Xenoliths in Basic-Ultrabasic Rocks of the Ioko-Dovyren Massif, Northern Baikal Region, RussiaDovyrenite, simplified formula Ca6Zr[Si2O7]2(OH)4, occurs as an accessory mineral in vein skarns developed in carbonate xenoliths in subvolcanic layered plagiodunite-troctolite series in the Ioko-Dovyren Massif of Proterozoic age, Northern Baikal Region, Buryatia, Russia. Dovyrenite is a late mineral of altered pyroxene and melilite-monticellite skarns. Associated minerals are Zr-bearing phases: fassaitic pyroxene, perovskite and hydrogarnets; and also monticellite, vesuvianite, diopside, foshagite, brucite, calzirtite, tazheranite, baghdadite, apatite, calcite, native bismuth, sphalerite, selenian galena, clausthalite, safflorite, rammelsbergite, pyrrhotite, pentlandite, valleriite, laitakarite, nickeline, nickel-skutterudite. The average structure of dovyrenite is orthorhombic, space group Pnnm, with subcell parameters A = 5.666(16) Å, B = 18.844(5) Å, C = 3.728(11) Å, V = 398.0(2) Å3 and Z = 1. Dovyrenite shows a new type of modular structure with stacking of the tobermorite-like and the rosenbuschite-like layers parallel to (010). Single-crystal structural data point to an incompletely occupied Ca(2) site from the rosenbuschite module which is confirmed by microprobe analyses: ZrO2 16.47, SiO2 32.83, TiO2 0.14, HfO2 0.16, Cr2O3 0.01, CaO 43.87, FeO 0.25, MgO 0.13, MnO 0.02, Nb2O3 0.03; total 99.38 wt% with calculated H2O. The empirical formula is (Ca5.73Fe0.03Mg0.02)σ5.78(Zr0.98Hf0.01Ti0.01)σ1Si4(O13.56OH0.44)σ14(OH)4. The presence of two types of OH group in the dovyrenite structure is corroborated by FTIR and Raman spectroscopy. Dovyrenite is an optically positive biaxial mineral: α 1.659(2), β 1.660(2); γ 1.676(2); 2Vz 30(5)° (measured), 28° (calculated). The coexistence of monticellite, foshagite and dovyrenite points to a narrow interval of crystallization 560-630°C under subvolcanic conditions (P < 108 Pa).

Estimation of polyhedral compressibilities and structural evolution of GdFeO3-type perovskites at high pressures

A new approach based on the bond-valence matching relation is developed to predict the detailed structural evolution of GdFeO3-type perovskites at high pressure from knowledge of the room-pressure structure and the high-pressure unit-cell parameters alone. The evolution of perovskite structures estimated in this way is in good agreement with the structure refinements available from high-pressure single-crystal diffraction measurements of a number of perovskites. The method is then extended to predict the structure of MgSiO3 perovskite at pressures for which no single-crystal structural data are available and the results are compared to ab initio quantum calculations of MgSiO3 perovskite up to 120 GPa.