Mechanism of thiolate-disulfide interchange reactions in biochemistry.
Both density functional theory (DFT) (B3LYP) and CCSD ab initio calculations were employed in a theoretical investigation of the mechanism of thiolate-disulfide exchange reactions. The reaction pathway for degenerate thiolate-disulfide exchange reactions with dimethyl disulfide has been shown to proceed through a SN2-like transition structure that is very close in energy to the corresponding trisulfur anionic intermediate ([delta-S-S-Sdelta(-)]). When relatively small substituents are involved, the level of theory must be increased to CCSD to make this rather subtle mechanistic distinction. With the more sterically hindered exchange reaction involving t-butyl mercaptide and di-t-butyl disulfide, the potential energy surface exhibits a distinct preference for the S(N)2 displacement pathway with an activation barrier of 9.8 kcal/mol. When corrections for solvent polarity are included (COSMO), an S(N)2 mechanism is also implicated in both polar and nonpolar solvents. DFT studies on thiolate-disulfide exchange, when the substituent is a model peptide, strongly support the intermediacy of a trisulfur intermediate that lies 10.7 kcal/mol below isolated reactants. A well depth of this magnitude should provide a sufficient lifetime of the intermediate to accommodate the requisite conformational adjustments that accompanies formation of the new disulfide bond.
Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA. rbach@udel.edu
Robert D
RD
Bach
Olga
O
Dmitrenko
Colin
C
Thorpe
D004220:Disulfides / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011789:Quantum Theory; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D004220:Disulfides; D013438:Sulfhydryl Compounds