Enzyme inhibitor modeling with TpZn complexes of functional hydroxamates and oximates

Salicylhydroxamic acid reacts with the enzyme model TpPh,MeZn-OH to form the O,O-chelating hydroxamate complex 1. The hydrogen bonding capacity of zinc enzyme bound hydroxamates is reproduced by cocrystallization of two molecules if 1 with two molecules of methanol and by cocrystallization of one molecule of TpPh,MeZn-acetohydroxamate with one molecule of 3-phenyl-5-methylpyrazole. The complex formed from TpPh,MeZn-OH and N-tosylproline hydroxamic acid, according to its spectra, contains the hydroxamate as an N,N-chelating ligand. In contrast, the oximate derived from pyruvic aldehyde does not act as a chelating ligand, but is monodentate via the oximate oxygen.

Salicylhydroxamic acid, acetohydroxamic acid, N-tosylproline hydroxamic acid and pyruvic aldehyde oxime react with the enzyme model TpPh,MeZn-OH to form complexes, which mimic the inhibition of zinc enzymes. The complexes display a wide structural variety, the main feature of which is the hydrogen bonding capacity of the hydroxamate ligands.Figure optionsDownload as PowerPoint slide