Theoretical insights into the mechanism for thiol/disulfide exchange

• Type: Article in International Scientific Journal
• Date: 2004

Authors

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

Journal

Title: Chemistry - A European Journal

Vol. 10

Pages: 257-266

ISSN: 0947-6539

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 227 Citations

Scopus - 236 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10