TY - JOUR
T1 - Thiolate exchange in [TmR]ZnSR′ complexes and relevance to the mechanisms of thiolate alkylation reactions involving zinc enzymes and proteins
AU - Melnick, Jonathan G.
AU - Zhu, Guang
AU - Buccella, Daniela
AU - Parkin, Gerard
N1 - Funding Information:
We thank the National Institutes of Health (Grant GM46502) for support of this research.
PY - 2006/5
Y1 - 2006/5
N2 - The zinc and cadmium thiolate complexes [ TmBu t ] MSCH2 C ( O ) N ( H ) Ph (M = Zn, Cd) may be obtained via treatment of the respective methyl complex [ TmBu t ] MMe with PhN(H)C(O)CH2SH. The molecular structure of [ TmBu t ] ZnSCH2 C ( O ) N ( H ) Ph has been determined by X-ray diffraction, thereby demonstrating the presence of an intramolecular N-H ⋯ S hydrogen bond between the amide N-H group and thiolate sulfur atom. [ TmBut ] ZnSCH2 C ( O ) N ( H ) Ph mimics the function of the Ada DNA repair protein by undergoing alkylation with MeI to give [ TmBu t ] ZnI and MeSCH2C(O)N(H)Ph. A series of crossover experiments and 1H NMR magnetization transfer studies establish that thiolate exchange between [TmR]ZnSR′ derivatives is facile in this system, an observation that supports the previous suggestion that the alkylation of [TmPh]ZnSCH2C(O)N(H)Ph by MeI may proceed via a sequence that involves dissociation of [PhN(H)C(O)CH2S]-.
AB - The zinc and cadmium thiolate complexes [ TmBu t ] MSCH2 C ( O ) N ( H ) Ph (M = Zn, Cd) may be obtained via treatment of the respective methyl complex [ TmBu t ] MMe with PhN(H)C(O)CH2SH. The molecular structure of [ TmBu t ] ZnSCH2 C ( O ) N ( H ) Ph has been determined by X-ray diffraction, thereby demonstrating the presence of an intramolecular N-H ⋯ S hydrogen bond between the amide N-H group and thiolate sulfur atom. [ TmBut ] ZnSCH2 C ( O ) N ( H ) Ph mimics the function of the Ada DNA repair protein by undergoing alkylation with MeI to give [ TmBu t ] ZnI and MeSCH2C(O)N(H)Ph. A series of crossover experiments and 1H NMR magnetization transfer studies establish that thiolate exchange between [TmR]ZnSR′ derivatives is facile in this system, an observation that supports the previous suggestion that the alkylation of [TmPh]ZnSCH2C(O)N(H)Ph by MeI may proceed via a sequence that involves dissociation of [PhN(H)C(O)CH2S]-.
KW - Ada DNA repair protein
KW - Thiolate alkylation
KW - Thiolate dissociation
KW - Zinc enzymes and proteins
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U2 - 10.1016/j.jinorgbio.2005.12.023
DO - 10.1016/j.jinorgbio.2005.12.023
M3 - Article
C2 - 16516971
AN - SCOPUS:33745384266
SN - 0162-0134
VL - 100
SP - 1147
EP - 1154
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 5-6
ER -