Theoretical insights into the mechanism for thiol/disulfide exchange

• Tipo: Artigo em Revista Científica Internacional
• Data: 2004

Autores

Fernandes, PA (Autor) FCUP; Ramos, MJ (Autor) FCUP

Revista

Título: Chemistry - A European Journal

Vol. 10

Páginas: 257-266

ISSN: 0947-6539

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 227 Citações

Scopus - 236 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-000-BZG

DOI: 10.1002/chem.200305343

Abstract (EN): The mechanism for thiol/disulfide exchange has been studied with high-level theoretical calculations. Free energies, transition structures, charge densities, and solvent effects along the reaction pathway have been determined for the first time. Mechanistic results agree with experimental data, and support the idea that the thiolate is the reacting species and that the reaction indeed proceeds through an uncomplicated S(N)2 transition state. The transition structures have the charge density evenly concentrated in the at-tacking and leaving sulfur atoms. The charge densities allow us to rationalize the solvent effects. As transition structures have the charge density more widely distributed than reactants, hydrophobic environments catalyze the reaction. The effect can be so dramatic that disulfide exchange inside the active site of ribonucleotide reductase is estimated to be catalyzed 10(3) times faster than the reaction in water. It was also found that attack by thiol is much faster than previously assumed, if mediated through water chains. Although the present results, as well as experimental data, still suggest that thiolate is the main reaction species, water-mediated thiol attack is almost kinetically competitive, and can eventually become competitive under specific experimental conditions.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10