Biomedical subjects

David Balcells

Publications and source records attributed to David Balcells.

6 recordsLinked to original sources

PubMed2006

Mechanism of the base-assisted displacement of chloride by alcohol in sulfinyl derivatives.

A computational study with density functional theory (DFT) is carried out on the reaction between methyl sulfinyl chloride (MSC) and methanol in the presence of trimethylamine, a process which is a general model for two different methods used in practice for the obtention of chiral sulfoxides through dynamic kinetic resolution. Two mechanistic options are considered: in one of them, chloride is initially displaced by the base (ion pair mechanism), whereas in the other, chloride stays bound to sulfur until its final displacement by methoxy (neutral mechanism). In both cases, the approach of the alcohol to sulfur is coupled with a hydrogen transfer from methanol to the oxo group of MSC in a single concerted transition state. The presence of a trimethylamine molecule facilitates substantially the reaction by reducing the nucleophilic substitution barrier by more than 10 kcal/mol through the formation of a N-H bond with the hydrogen atom being transferred. The neutral mechanism presents a free energy barrier lower than the ion pair alternative and is thus preferred.

Alcohols↗

PubMed2005

Computational rationalization of the dependence of the enantioselectivity on the nature of the catalyst in the vanadium-catalyzed oxidation of sulfides by hydrogen peroxide.

A computational study with the IMOMM(Becke3LYP:MM3) method is carried out on the mechanism of the enantioselective reaction of complex V(O)(L)(OOH), L= bulky tridentate Schiff base, and bis(tert-butyl) disulfide. The reaction with a given L ligand A is first systematically studied: different conformers of the catalyst are optimized, and the large number of associated transition states are systematically searched. The study is then extended to the geometry optimization of selected transition states associated to other ligands B, C, and D, similar to A but differing in the nature of certain substituents R1, R2, R3. The experimental trends in selectivity for catalysts based on ligands A to D are faithfully reproduced by the calculations. Analysis of the computational results leads finally to the formulation of a simple model that can explain one of the most remarkable aspect of this reaction, namely the large effect on enantioselectivity of ligands seemingly far from each other in the catalyst.

Journal Article↗

PubMed2004

Base-catalyzed inversion of chiral sulfur centers. A computational study.

[reaction: see text] A theoretical study on the pyramidal inversion of the chiral sulfur compounds SO(X)(Me) (X = Cl, OMe, p-MePh) has been carried out by means of the DFT(Becke3LYP) method. Our results reveal that in the case of X = Cl, an organic tertiary amine such as NMe(3) can catalyze the racemization. The base-catalyzed inversion of SO(Cl)(Me) is proposed as a feasible dynamic kinetic resolution mechanism for the synthesis of chiral sulfoxides by the DAG method.

Journal Article↗

PubMed2003

An oscillating C2(2-) unit inside a copper rectangle.

[Cu4(mu-dppm)4(mu4-eta1,eta2-C[triple bond]C-)]2+ has been shown by 31P and 1H NMR studies to undergo two fluxional processes in solution, the oscillation of the C[triple bond]C2- unit inside the copper rectangle and the flipping of the diphosphines, and this has been supported by DFT(B3LYP) calculations.

Journal Article↗

PubMed2003

Density functional study on the mechanism of the vanadium-catalyzed oxidation of sulfides by hydrogen peroxide.

A computational study with the Becke3LYP method is carried out on the mechanism of the reaction of complexes V(O)(L)(OOH) and V(O)(LH)(OO) (L = O(CH)(3)N(CH(2))(2)O) with CH(3)S-SCH(3), a system that stands as a model for experimental systems where the metal complex contains larger chelating Schiff bases and the substrate is bis(tert-butyl) disulfide. The different possible isomers of both the hydroperoxo V(O)(L)(OOH) and the peroxo V(O)(LH)(OO) forms of the catalyst are explored, and the reactivity of the most stable among them with the dimethyl disulfide substrate is studied through location of the corresponding transition states. A large variety of reactive paths happen to exist, though in all cases the reaction takes place through a direct transfer process, with the simultaneous formation of the S-O bond and breaking of the O-O bond being the rate-limiting step.

Journal Article↗

PubMed2003

Some critical issues in the application of quantum mechanics/molecular mechanics methods to the study of transition metal complexes.

The application of quantum mechanics/molecular mechanics (QM/MM) methods in transition metal chemistry is growing steadily. It becomes therefore appropriate to assess the importance of a number of technical issues associated to their implementation. This work presents the discussion of several of these issues, including the eventual need for conformational searches, the choice of the MM force field and the possibility of its tuning. The examples presented here prove that a proper handling of these technical aspects can lead to an improvement in the efficiency and quality of QM/MM calculations.

Disulfides↗