Modeling the Active Site Chemistry of Liver Alcohol Dehydrogenase: Mononuclear Zinc Methanol and <i>N,N</i>-Dimethylformamide Complexes of a Nitrogen/Sulfur Ligand Possessing an Internal Hydrogen Bond Donor

Abstract

Using a novel nitrogen/sulfur ligand possessing a single internal hydrogen bond donor (bmapa, N,N-bis-(2-methylthio)ethyl-N-(6-amino-2-pyridylmethyl)amine), mononuclear zinc complexes possessing a single zinc-bound methanol ([(bmapa)Zn(MeOH)](ClO4)2·MeOH, 1·MeOH) or N,N-dimethylformamide ([(bmapa)Zn(DMF)](ClO4)2, 2) molecule have been synthesized and structurally characterized. These complexes are structurally relevant to substrate- and inhibitor-bound forms of liver alcohol dehydrogenase (LADH) and exhibit hydrogen-bonding interactions akin to those found in the active site of LADH.