Thiolate exchange in [TMR]ZnSR ' complexes and relevance to the mechanisms of thiolate alkylation reactions involving zinc enzymes and proteins

摘要

The zinc and cadmium thiolate complexes [Tm-Bui] MSCH2C(O)N(H)Ph (M = Zn, Cd) may be obtained via treatment of the respective methyl complex [Tm-Bui]MMe with PhN(H)C(O)CH2SH. The molecular structure of [Tm-Bui]ZnSCH2C(O)N(H)Ph has been determined by X-ray diffraction, thereby demonstrating the presence of an intramolecular N-(HS)-S-... hydrogen bond between the amide N-H group and thiolate sulfur atom. [Tm-Bui]ZnSCH2C(O)N(H)Ph mimics the function of the Ada DNA repair protein by undergoing alkylation with MeI to give [Tm-Bui]ZnI and MeSCH2C(O))N(H)Ph. A series of crossover experiments and H-1 NMR magnetization transfer studies establish that thiolate exchange between [Tm-R]ZnSR' derivatives is facile in this system, an observation that supports the previous suggestion that the alkylation of [Tm-Ph]ZnSCH2C(O))N(H)Ph by MeI may proceed via a sequence that involves dissociation of [PhN(H)C(O)CH2S](-). (c) 2006 Elsevier Inc. All rights reserved.