Fate of three anti-influenza drugs during ozonation of wastewater effluents - degradation and formation of transformation products.

Anti-influenza drugs constitute a key component of pandemic preparedness plans against influenza. However, the occurrence of such drugs in water environments, the potential of resistance development in the natural hosts, and the risk for transmission of antiviral resistance to humans call for measures to increase removal in wastewater treatment plants (WWTPs). In this study, removal of three anti-influenza drugs; amantadine (AM), oseltamivir carboxylate (OC) and zanamivir (ZA), and formation/removal of their transformation products during ozonation of wastewater effluents from two Swedish WWTPs in Uppsala and Stockholm were studied.

A computational study of the CO dissociation in cyclopentadienyl ruthenium complexes relevant to the racemization of alcohols.

The formation of an active 16-electron ruthenium sec-alkoxide complex via loss of the CO ligand is an important step in the mechanism of the racemization of sec-alcohols by (η(5)-Ph(5)C(5))Ru(CO)(2)X ruthenium complexes with X = Cl and O(t)Bu. Here we show with accurate DFT calculations the potential energy profile of the CO dissociation pathway for a series of relevant (η(5)-Ph(5)C(5))Ru(CO)(2)X complexes, where X = Cl, O(t)Bu, H and COO(t)Bu. We have found that the CO dissociation energy increases in the following order: O(t)Bu (lowest), Cl, COO(t)Bu and H (highest).

Combinatorial reshaping of the Candida antarctica lipase A substrate pocket for enantioselectivity using an extremely condensed library.

A highly combinatorial structure-based protein engineering method for obtaining enantioselectivity is reported that results in a thorough modification of the substrate binding pocket of Candida antarctica lipase A (CALA). Nine amino acid residues surrounding the entire pocket were simultaneously mutated, contributing to a reshaping of the substrate pocket to give increased enantioselectivity and activity for a sterically demanding substrate. This approach seems to be powerful for developing enantioselectivity when a complete reshaping of the active site is required.

Directed evolution of an enantioselective lipase with broad substrate scope for hydrolysis of alpha-substituted esters.

A variant of Candida antarctica lipase A (CalA) was developed for the hydrolysis of alpha-substituted p-nitrophenyl esters by directed evolution. The E values of this variant for 7 different esters was 45-276, which is a large improvement compared to 2-20 for the wild type. The broad substrate scope of this enzyme variant is of synthetic use, and hydrolysis of the tested substrates proceeded with an enantiomeric excess between 95-99%.

On the possibility of catalytic reduction of carbonyl moieties with tris(pentafluorophenyl)borane and H2: a computational study.

The study thoroughly examines the Gibbs free energy surfaces of a new mechanism for reduction of ketones/aldehydes by tris(pentafluorophenyl)borane (1) and H(2). Key elements of the proposed mechanism are the proton and the hydride transfer steps similar to Stephan's catalytic reduction of imines by 1. The proton is transferred to the ketone/aldehyde in the process of H(2) cleavage by the carbonyl-borane couple and the hydride is transferred in a nucleophilic attack on the carbonyl carbon by the hydridoborate in the ionic pair, [HOCRR'](+)[HB(C(6)F(5))(3)](-).

CO assistance in ligand exchange of a ruthenium racemization catalyst: identification of an acyl intermediate.

An acyl intermediate in the activation of eta(5)-(Ph(5)Cp)Ru(CO)(2)Cl by t-BuOK was identified by means of in situ FT-IR measurements and NMR spectroscopy. This strongly supports the conclusion that the ligand exchange takes place via CO assistance, i.e.

Directed evolution of Candida antarctica lipase A using an episomaly replicating yeast plasmid.

We herein report the first directed evolution of Candida antarctica lipase A (CalA), employing a combinatorial active-site saturation test (CAST). Wild-type CalA has a modest E-value of 5.1 in kinetic resolution of 4-nitrophenyl 2-methylheptanoate.

Racemization of alcohols catalyzed by [RuCl(CO)2(eta(5)-pentaphenylcyclopentadienyl)]--mechanistic insights from theoretical modeling.

Two possible pathways of inner-sphere racemization of sec-alcohols by using the [RuCl(CO)(2)(eta(5)-pentaphenylcyclopentadienyl)] catalyst (1) have been thoroughly investigated by means of density function calculations. To be able to racemize alcohols, catalyst 1 needs to have a free coordination site on the metal. This can be achieved either by a eta(5)-->eta(3) ring slippage or by dissociation of a carbon monoxide (CO) ligand.

Influence of delta-functional groups on the enantiorecognition of secondary alcohols by Candida antarctica lipase B.

The selectivity of acetylation of delta-functionalized secondary alcohols catalyzed by Candida antarctica lipase B has been examined by molecular dynamics. The results from the simulation show that a delta-alcohol functionality forms a hydrogen bond with the carbonyl group of Thr 40. This interaction stabilizes the tetrahedral intermediate and thus leads to selective acetylation of the R enantiomer.

Synthesis and optical resolution of an allenoic acid by diastereomeric salt formation induced by chiral alkaloids.

A synthetic procedure for the preparation of 4-cyclohexyl-2-methyl-buta-2,3-dienoic acid in the two optically active forms has been developed. Synthesis of the racemic allenoic acid was made by an efficient route with good overall yield. Resolution of the enantiomers was achieved by forming the cinchonidine and cinchonine diastereomeric salt, respectively, and the enantiomers were isolated in up to 95% enantiomeric excess.