QM/MM study of the reaction mechanism of sulfite oxidase.

Sulfite oxidase is a mononuclear molybdenum enzyme that oxidises sulfite to sulfate in many organisms, including man. Three different reaction mechanisms have been suggested, based on experimental and computational studies. Here, we study all three with combined quantum mechanical (QM) and molecular mechanical (QM/MM) methods, including calculations with large basis sets, very large QM regions (803 atoms) and QM/MM free-energy perturbations.

A quantum-mechanical study of the reaction mechanism of sulfite oxidase.

The oxidation of sulfite to sulfate by two different models of the active site of sulfite oxidase has been studied. Both protonated and deprotonated substrates were tested. Geometries were optimized with density functional theory (TPSS/def2-SV(P)) and energies were calculated either with hybrid functionals and large basis sets (B3LYP/def2-TZVPD) including corrections for dispersion, solvation, and entropy, or with coupled-cluster theory (LCCSD(T0)) extrapolated toward a complete basis set.

Understanding the Chemistry of Lead at a Molecular Level: The Pb(II) 6s6p Lone Pair Can Be Bisdirected in Proteins.

Pb(2+) complexes can attain several different topologies, depending of the shape of the Pb 6s6p lone pair. In this paper, we study structures with a bisdirected Pb lone pair with quantum mechanics (DFT) and QM/MM calculations. We study small symmetric Pb(2+) models to see what factors are needed to get a bisdirected lone pair.

Role of Cation Polarization in holo- and hemi-Directed [Pb(H2O)n](2+) Complexes and Development of a Pb(2+) Polarizable Force Field.

Reduced Variational Space (RVS) calculations are reported that afford insight into the energetic origins of the hemi- and holo-directing behavior of [Pb(H2O)n](2+) complexes. It is shown that the distribution of ligands around the Pb(2+) center arises from a delicate balance between the first-order Coulomb plus exchange-repulsion energy that favors holo-directionality, and the second-order charge transfer plus polarization term that favors hemi-directionality. It is additionally demonstrated that the pseudopotential/basis set combination used to study such complexes should be carefully selected, as artifacts can arise when using large-core pseudopotentials.

Application of the topological analysis of the electronic localization function to archetypical [Pb(II)Ln]p complexes: the bonding of Pb2+ revisited.

The coordination of neutral ligands (L = OC, HCN, NH3, PH3, SH2, HNCO and H2O) to Pb2+ is investigated and analyzed by means of the topological analysis of the Electronic Localization Function (ELF). It is shown that the mean charge density of the V(Pb) basin ((V(Pb))) can reach a ligand-independent limiting value from n = 6, a coordination number from which the [PbL(n)]2+ complexes adopt holodirected structures. The investigations performed on anionic series (L = HS-, OH-, CN-, F-, Cl-, and Br-) lead to optimized stable structures in which the coordination number does not exceed n = 4, even in the presence of a model aqueous solvent.

Straightforward synthesis of (S)- and (R)-alpha-trifluoromethyl proline from chiral oxazolidines derived from ethyl trifluoropyruvate.

[Structure: see text] A concise synthesis of both enantiomers of alpha-Tfm-proline and (S)-alpha-Tfm-prolinol from ethyl trifluoropyruvate is reported. The key step is a diastereoselective allylation reaction of ethyl trifluoropyruvate and (R)-phenylglycinol-based oxazolidines or imine. The lactone obtained by cyclization of the resulting hydroxy ester proved to be a valuable intermediate for the synthesis of (S)-alpha-Tfm-allylglycine and (S)-alpha-Tfm-norvaline in enantiopure form.