Ultrasonic Film Rehydration Synthesis of Mixed Polylactide Micelles for Enzyme-Resistant Drug Delivery Nanovehicles

A facile technique for the preparation of mixed polylactide micelles from amorphous poly-D,L-lactide-block-polyethyleneglycol and crystalline amino-terminated poly-L-lactide is described. In comparison to the classical routine solvent substitution method, the ultrasonication assisted formation of polymer micelles allows shortening of the preparation time from several days to 15–20 min. The structure and morphology of mixed micelles were analyzed with the assistance of electron microscopy, dynamic and static light scattering and differential scanning calorimetery. The resulting polymer micelles have a hydrodynamic radius of about 150 nm and a narrow size distribution. The average molecular weight of micelles was found to be 2.1 × 107 and the aggregation number was calculated to be 6000. The obtained biocompatible particles were shown to possess low cytotoxicity, high colloid stability and high stability towards enzymatic hydrolysis. The possible application of mixed polylactide micelles as drug delivery vehicles was studied for the antitumor hydrophobic drug paclitaxel. The lethal concentration (LC50) of paclitaxel encapsulated in polylactide micelles was found to be 42 ± 4 µg/mL—a value equal to the LC50 of paclitaxel in the commercial drug Paclitaxel-Teva

CuCoMgAlO_x Mixed Oxides as Selective Catalysts for the Hydrogenation of Furan Compounds

Single phase CuCoMgAl-layered hydroxides were obtained by making fine adjustment to their composition through changing the (Co + Cu)/Mg = 0.5; 1; 2; 3 and Co/Cu = 0.5; 1; 2 ratios. The rise of Co/Cu in systems contributed to the increase in their thermal stability. CuCoMgAl-catalysts showed high selectivity of carbonyl group hydrogenation in furfural and 5-hydroxymethylfurfural. In furfural hydrogenation, the selectivity to furfuryl alcohol was more than 99%, and in 5-hydroxymethylfurfural hydrogenation, the selectivity to 2,5-hydroxymethyl furfural was 95%. The surface of the samples with different Co/Cu after calcination and reduction was the same and had a «core-shell» structure (TEM). «Core» consisted of Cu and Co metallic particles. «Shell» consisted of CuCoMgAlOx mixed no-stoichiometric spinel oxides. There was no sintering or change in size of the metallic particles after the reaction. For the sample with Co/Cu = 1, their phase composition after reaction remained unchangeable. The increase of Co/Cu led to the formation of an X-ray amorphous phase after the reaction. This suggests the decrease in structural stability of this sample. The obtained results prove the prospects of using bimetallic CoCu-systems for hydrogenation of furan aldehydes, and opens up new directions for further research and improvement

Synthesis of CuAl-, CoAl-, and CuCoAl-Catalysts from Layered Hydroxides for Furfural Hydrogenation

Catalysts based on CuAl-, CoAl-, and CuCoAl-layered hydroxides with M2+/Al = 2 and Cu/Co = 1 molar ratio were obtained. The effect of amount of cobalt on the structural properties, morphology, surface cations distribution, oxide phase formation, thermal stability of the samples and reduction of metals from them was studied. The effect of reaction conditions (temperature, time, pressure, solvent) and conditions of preliminary treatment of catalysts on their catalytic properties in furfural hydrogenation was established. High selectivity to furfuryl alcohol was observed for all the samples irrespective of pretreatment and reaction conditions. The synergetic effect in furfural hydrogenation between Co and Cu in the CuCoAlOx catalysts was revealed when ethanol is used as a solvent

An Efficient Technique for Ammonia Capture in the Haber–Bosch Process Loop—Membrane-Assisted Gas Absorption

The present study continues the development and enhancement of a highly efficient unique hybrid technique—membrane-assisted gas absorption in designing the separation unit, which provides the improvement in mass-transfer of a target component during the ammonia capture process from a process loop of the Haber–Bosch technological route. In order to minimize the absorbent volume to membrane area ratio, the special separation cell was designed based on a combination of two types of hollow fiber membranes, dense gas separation membrane and porous pervaporation membrane. The separation performance tests were implemented under two sets of conditions, sweeping the bore (permeate) side of a cell with helium and hydrogen-nitrogen mix. For both cases, the membrane-assisted gas absorption cell demonstrated high separation efficiency, and the ammonia concentration in the permeate was never lower than 81 mol%; meanwhile, under the hydrogen-nitrogen bore sweep conditions, the ammonia concentration in the permeate reached 97.5 mol% in a single-step process. Nevertheless, there is a product purity–recovery rate trade-off, which is a typical issue for separation processes

Multiscale computation delivers organophosphorus reactivity and stereoselectivity to immunoglobulin scavengers

Quantum mechanics/molecular mechanics (QM/MM) maturation of an immunoglobulin (Ig) powered by supercomputation delivers novel functionality to this catalytic template and facilitates artificial evolution of biocatalysts. We here employ density functional theory-based (DFT-b) tight binding and funnel metadynamics to advance our earlier QM/MM maturation of A17 Ig-paraoxonase (WTIgP) as a reactibody for organophosphorus toxins. It enables regulation of biocatalytic activity for tyrosine nucleophilic attack on phosphorus. The single amino acid substitution l-Leu47Lys results in 340-fold enhanced reactivity for paraoxon. The computed ground-state complex shows substrate-induced ionization of the nucleophilic l-Tyr37, now H-bonded to l-Lys47, resulting from repositioning of l-Lys47. Multiple antibody structural homologs, selected by phenylphosphonate covalent capture, show contrasting enantioselectivities for a P-chiral phenylphosphonate toxin. That is defined by crystallographic analysis of phenylphosphonylated reaction products for antibodies A5 and WTIgP. DFT-b analysis using QM regions based on these structures identifies transition states for the favored and disfavored reactions with surprising results. This stereoselection analysis is extended by funnel metadynamics to a range of WTIgP variants whose predicted stereoselectivity is endorsed by experimental analysis. The algorithms used here offer prospects for tailored design of highly evolved, genetically encoded organophosphorus scavengers and for broader functionalities of members of the Ig superfamily, including cell surface-exposed receptors