Intramolecular NH···S Hydrogen Bonding in the Zinc Thiolate Complex [TmPh]ZnSCH2C(O)NHPh: A Mechanistic Investigation of Thiolate Alkylation as Probed by Kinetics Studies and by Kinetic Isotope Effects
| Autor: | Melissa M. Morlok, Duncan A. Quarless, Kevin E. Janak, Guang Zhu, Gerard Parkin |
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| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Alkylation Stereochemistry Crystallography X-Ray Biochemistry Medicinal chemistry Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Amide Kinetic isotope effect Organometallic Compounds Molecule Sulfhydryl Compounds Molecular Structure Hydrogen bond Chemistry Ligand Temperature Hydrogen Bonding General Chemistry Associative substitution Kinetics Zinc Intramolecular force |
| Zdroj: | Journal of the American Chemical Society. 127:14039-14050 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/ja0536670 |
| Popis: | The zinc thiolate complex [Tm(Ph)]ZnSCH2C(O)N(H)Ph, which features a tetrahedral [ZnS4] motif analogous to that of the Ada DNA repair protein, may be obtained by the reaction of Zn(NO3)2 with [Tm(Ph)]Li and Li[SCH2C(O)N(H)Ph] ([Tm(Ph)] = tris(2-mercapto-1-phenylimidazolyl)hydroborato ligand). Structural characterization of [Tm(Ph)]ZnSCH2C(O)N(H)Ph by X-ray diffraction demonstrates that the molecule exhibits an intramolecular N-H...S hydrogen bond between the amide N-H group and thiolate sulfur atom, a structure that is reproduced by density functional theory (DFT) calculations. The thiolate ligand of [Tm(Ph)]ZnSCH2C(O)N(H)Ph is subject to alkylation, a reaction that is analogous to the function of the Ada DNA repair protein. Specifically, [Tm(Ph)]ZnSCH2C(O)N(H)Ph reacts with MeI to yield PhN(H)C(O)CH2SMe and [Tm(Ph)]ZnI, a reaction which is characterized by second-order kinetics that is consistent with either (i) an associative mechanism or (ii) a stepwise dissociative mechanism in which the alkylation step is rate determining. Although the kinetics studies are incapable of distinguishing between these possibilities, a small normal kinetic isotope effect of kH/kD = 1.16(1) at 0 degrees C for the reaction of [Tm(Ph)]ZnSCH2C(O)N(H*)Ph (H* = H, D) with MeI is suggestive of a dissociative mechanism on the basis of DFT calculations. In particular, DFT calculations demonstrate that a normal kinetic isotope effect requires thiolate dissociation because it results in the formation of [PhN(H)C(O)CH2S]- which, as an anion, exhibits a stronger N-H...S hydrogen bonding interaction than that in [Tm(Ph)]ZnSCH2C(O)N(H)Ph. Correspondingly, mechanisms that involve direct alkylation of coordinated thiolate are predicted to be characterized by kH/kDor = 1 because the reaction involves a reduction of the negative charge on sulfur and hence a weakening of the N-H...S hydrogen bonding interaction. |
| Databáze: | OpenAIRE |
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