PREPARATION OF CHITOSAN GRAFT COPOLYMERS AND STUDY OF THEIR WATER-SWELLING PROPERTIES

In this work, graft copolymers of chitosan with trimethylmethacryloxyethylammonium methyl sulfate were synthesized by the method of controlled radical polymerization, and it was found that replacing the dimethylformamide aprotic solvent with water increases the degree of grafting. With the aim of the possible use of chitosan copolymers as a functional component for regulating the water-swelling properties of elastomers, the kinetics of swelling of the samples was investigated. An increase in the degree of swelling of the copolymers in comparison with the initial chitosan was revealed, and the influence of the molecular weight and the conditions of their synthesis was established.

Stabilization of Haloalkane Dehalogenase Structure by Interfacial Interaction with Ionic Liquids

Ionic liquids attracted interest as green alternatives to replace conventional organic solvents in protein stability studies. They can play an important role in the stabilization of enzymes such as haloalkane dehalogenases that are used for biodegradation of warfare agents and halogenated environmental pollutants. Three-dimensional crystals of haloalkane dehalogenase variant DhaA80 (T148L+G171Q+A172V+C176F) from Rhodococcus rhodochrous NCIMB 13064 were grown and soaked with the solutions of 2-hydroxyethylammonium acetate and 1-butyl-3-methylimidazolium methyl sulfate. The objective was to study the structural basis of the interactions between the ionic liquids and the protein. The diffraction data were collected for the 1.25 Å resolution for 2-hydroxyethylammonium acetate and 1.75 Å resolution for 1-butyl-3-methylimidazolium methyl sulfate. The structures were used for molecular dynamics simulations to study the interactions of DhaA80 with the ionic liquids. The findings provide coherent evidence that ionic liquids strengthen both the secondary and tertiary protein structure due to extensive hydrogen bond interactions.

Pretreatment of pussy willow and Korean pine using various ionic liquids and their mixtures with organic solvents for enzymatic saccharification

Different ionic liquids (ILs) and their mixtures with organic solvents (OSs) were investigated to determine their effects on pretreatment for enzymatic saccharification of pussy willow and Korean pine. Combinations of three ILs, namely (1-ethyl-3-methylimidazolium acetate ([EMIM]Ac), 1-butyl-3-methylimidazolium bromide ([BMIM]Br), and 1,3-dimethylimidazolium methyl sulfate ([MMIM]MeSO4)) and three OSs (N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMAc), and dimethyl sulfoxide (DMSO)) were used. Acremonium cellulase and Optimash BG were used for enzymatic saccharification. The viscosity of ILs and their mixtures with OSs was reduced by adding and increasing the OS amount in mixtures. The viscosity of [BMIM]Br was considerably decreased by the addition of OSs. For both species, the water-soluble fractions (WSFs) obtained using pure ILs decreased with increasing OS content in mixtures. For all co-solvent systems, the WSFs for pussy willow were twice as large as those for Korean pine. For both species, the yields of glucose and xylose were higher for [EMIM]Ac and its mixtures with OSs than for [BMIM]Br, [MMIM]MeSO4, and their mixtures. However, only small differences between glycan and xylose yields among the products pretreated by [BMIM]Br, [MMIM]MeSO4, and their mixtures were observed. The overall xylose yields for pussy willow were higher than those for Korean pine for all pretreatments because xylan is the main hemicellulose component of hardwood.

Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters

Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs.

Rational design, supramolecular synthesis and solid state characterization of two bicomponent solid forms of mebendazole

MBZ methyl sulfate and perchlorate were designed based on the statistical probability of the formation of an R22(8) supramolecular heterosynthon.