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The mechanism for [H.sub.2] cleavage in NeFe-hydrogenase is reinvestigated with large models by using both hybrid density functional theory (DFT) by itself, or in a quantum mechanics (QM)/molecular mechanics (MM) scheme following the ONIOM approach. The studies have shown that the ONIOM results for the reaction mechanism in NiFe-hydrogenase had to be corrected by large model DFT results, which is due to overestimation of polarization effects of the QM region by the MM region.

The molecular dynamics (MD) simulations were used to study residues in and surrounding the active site and domain movements to gain insight into the role of catalytic mechanism of wild type Escherichia coli biotin carboxylase. The results obtained for the active-site interactions and dynamics of WT biotin carboxylase provide the insight into the design and interpretation of further experiments.

Friedel-Crafts acylation has been known since the 1870s, and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually performed with carboxylic acid chlorides or anhydrides, while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55-96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations.

In the presence of a chiral lithium N,P amide, alkylation of benzaldehyde results in an enantioselective formation of 1-phenyl-pentanol. This stereoselective addition reaction has herein been studied using dispersion-corrected density functional theory. For five different chiral ligands originating from amino acids the resulting enantioselectivity has been computationally determined and compared with experimentally available enantiomeric ratios (e.r.). In all cases the experimentally preferred enantiomer could be reproduced by the computational model. The selectivity trend among the ligands was found strongly sensitive to the amount of dispersion correction included. The origin of selectivity in the alkylation reaction is found to be composed of many combined interactions. For the most selective ligand 2A the most important factors found, which are favouring the (R)-TS, are a CH-π interaction between benzaldehyde-dimethyl ether (DME), stronger Li-solvation, and Li-π interactions with the phenyl ring in the backbone of the chiral lithium N,P amide. In addition, solvation by the bulk solvent and the size of the substituent on the nitrogen are also found important factors for the enantioselectivity., (This journal is © The Royal Society of Chemistry 2012)

An evaluation of a dispersion-corrected density functional theory method (B3LYP-DCP) [I.D. Mackie, G.A. DiLabio, Interactions in large, polyaromatic hydrocarbon dimers: application of density functional theory with dispersion corrections, J. Phys. Chem. A 112 (2008) 10968-10976] for three systems of biochemical interest is presented. Firstly, structures and energies of isomers of the tripeptide Phe-Gly-Phe have been compared with CCSD(T)/CBS//RI-MP2/cc-pVTZ literature values. In the system aromatic interactions compete with XH-pi (X=C, N) interactions and hydrogen bonds which makes it a reliable model for proteins. The resulting mean absolute deviation between B3LYP-DCP and CCSD(T)/CBS relative energies is found to be 0.50 kcal mol(-1). Secondly, a phenylalanine derivative featuring a CH-pi interaction has been investigated. A comparison between the optimized geometry and X-ray crystal data shows that B3LYP-DCP accurately predicts the interaction between the two aromatic rings. Thirdly, the dipeptide Ac-Phe-Phe-NH(2) which contains an edge-to-face interaction between two aromatic rings has been studied. The study demonstrates the general applicability of the B3LYP-DCP method on systems which features interactions typically present in biochemical compounds., ((c) 2010 Elsevier Inc. All rights reserved.)