Synthesis and Coordinating Properties of Ligands Designed for Modeling of the Active Site Zinc of Liver Alcohol Dehydrogenase

Article abstract of DOI:10.1021/jo00293a039

Some tridentate ligands have been prepared for coordination of zinc(II) ions (or cobalt(II), which acts as a surrogate for Zn(II) ions) in a manner analogous to the coordination found in liver alcohol dehydrogenase.This entails coordination of the metal ion to two thiolates and an imidazole.The ligands must be sufficiently sterically hindered to prevent thiolate from acting as a bridging ligand between two metal ions.For some aspects of this work pyridine was used instead of imidazole.A trisubstituted benzene derivative, 3,5-bis(3-mercaptopropoxy)-N-<2-(1H-imidazol-4-yl)ethyl>benzamide (7) was prepared.Zn(II) complexes with 7 could not be characterized but the Co(II) complexes showed excellent spectral correlation with liver alcohol dehydrogenase in which Zn(II) has been replaced by Co(II).Several analogues of 7 have also been synthesized.Another ligand, 2,6-bis<(9-mercaptofluoren-9-yl)methyl>pyridine (17), does provide a monomeric Zn(II) complex.The synthesis and coordination of various analogues of this system have been examined.The bis-alcohol, 2,6-bis(2-methyl-2-hydroxypropyl)pyridine (24), gives a stable pentacoordinate complex with Zn(NO3)2 and two water molecules.