Modeling Zinc Enzyme Inhibition with Functional Thiolate Ligands

The blocking of zinc enzymes by thiolate-containing inhibitors was modeled by treating TpPh,MeZn−OH with functional
thiols. The latter were chosen such that they contain an additional donor function (COOH, COOR, NH2, NHR, OH)
in a position favorable for chelation. Of them, mercapto carboxylic acid esters were incorporated as thiolates. The
corresponding mercapto carboxylic acids, however, used only their carboxylate function for coordination. Various
mercapto amines, mercapto alcohols, and mercaptophenol were exclusively converted to thiolate ligands. The two
modes of inhibitor attachment, terminal or chelating, were observed equally frequently. As a rule, they occur as
alternatives for similar ligands. In case of 2-mercaptophenol they coexist in the crystalline state and in solution.
Hydrogen bonding, both intra- and intermolecular, seems to be a decisive factor determining the inhibitor attachments.
Its persistence in solution is underlined by the observation that TpPh,MeZn−hydroxythiophenolates are methylated
about 2 orders of magnitude slower than TpPh,MeZn−SPh itself.