Mechanistic insight into hydroxamate transfer reaction mimicking the inhibition of zinc-containing enzymes. Issue 33 (17th August 2020)

• Record Type: Journal Article
• Authors: Kwon, Nam; Suh, Jong-Min; Lim, Mi Hee; Hirao, Hajime; Cho, Jaeheung
• Is Part Of: Chemical science. Volume 11:Issue 33(2020)
• Page Start: 9017
• Page End: 9021
• Publication Date: 2020-08-17
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0sc02676j
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A hydroxamate transfer reaction between metal complexes has been investigated by a combination of experimental and theoretical studies. 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, [Co II (TBDAP)(CH3 C(–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.