Mechanistic insight into hydroxamate transfer reaction mimicking the inhibition of zinc-containing enzymes |
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| Authors: | Nam Kwon Jong-Min Suh Mi Hee Lim Hajime Hirao Jaeheung Cho |
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| Institution: | Department of Emerging Materials Science, DGIST, Daegu 42988 Korea.; Department of Chemistry, KAIST, Daejeon 34141 Korea ; Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Hong Kong |
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| Abstract: | A hydroxamate transfer reaction between metal complexes has been investigated by a combination of experimental and theoretical studies. A hydroxamate-bound cobalt(ii) complex bearing a tetradentate macrocyclic ligand, CoII(TBDAP)(CH3C(–NHO)O)]+ (1), is prepared by the reduction of a hydroximatocobalt(iii) complex with a biological reductant. Alternatively, 1 is accessible via a synthetic route for the reaction between the cobalt(ii) complex and acetohydroxamic acid in the presence of a base. 1 was isolated and characterized by various physicochemical methods, including UV-vis, IR, ESI-MS, and X-ray crystallography. The hydroxamate transfer reactivity of 1 was examined with a zinc complex, which was followed by UV-vis and ESI-MS. Kinetic and activation parameter data suggest that the hydroxamate transfer reaction occurs via a bimolecular mechanism, which is also supported by DFT calculations. Moreover, 1 is able to inhibit the activity against a zinc enzyme, i.e., matrix metalloproteinase-9. Our overall investigations of the hydroxamate transfer using the synthetic model system provide considerable insight into the final step involved in the inhibition of zinc-containing enzymes.A hydroxamate transfer reaction between metal complexes has been investigated by a combination of experimental and theoretical studies. |
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