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

Jonathan G. Melnick, Guang Zhu, Daniela Buccella, Gerard Parkin

Research output: Contribution to journalArticle

Abstract

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]-.

Original languageEnglish (US)
Pages (from-to)1147-1154
Number of pages8
JournalJournal of Inorganic Biochemistry
Volume100
Issue number5-6
DOIs
StatePublished - May 2006

Fingerprint

Alkylation
Zinc
Enzymes
Cadmium
Sulfur
Amides
Molecular structure
Magnetization
Hydrogen bonds
Proteins
Repair
Nuclear magnetic resonance
Derivatives
X ray diffraction
Atoms
DNA
Molecular Structure
X-Ray Diffraction
DNA Repair
Hydrogen

Keywords

  • Ada DNA repair protein
  • Thiolate alkylation
  • Thiolate dissociation
  • Zinc enzymes and proteins

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry

Cite this

Thiolate exchange in [TmR]ZnSR′ complexes and relevance to the mechanisms of thiolate alkylation reactions involving zinc enzymes and proteins. / Melnick, Jonathan G.; Zhu, Guang; Buccella, Daniela; Parkin, Gerard.

In: Journal of Inorganic Biochemistry, Vol. 100, No. 5-6, 05.2006, p. 1147-1154.

Research output: Contribution to journalArticle

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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]-.

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