Bioinorganic chemistry of group 12 complexes supported by tetradentate tripodal Ligands having internal hydrogen-bond donors

Inspired by the proposed role of secondary hydrogen-bonding interactions in modulating the chemistry of mononuclear zinc centers in metalloenzymes, zinc complexes supported by tetradentate tripodal ligands having one or more internal hydrogen-bond donors have been prepared, characterized, and investigated for biologically relevant reactivity. Complexes of this class have been examined in terms of water activation and CO2 reactivity, alcohol/alkoxide coordination, and amide methanolysis and phosphate ester hydrolysis reactivity. The results of these studies indicate that the presence of internal hydrogen-bond donors will lower the pK(a) of a zinc-bound water molecule, stabilize zinc alkoxide species with respect to hydrolysis, and enhance the phosphate ester cleavage reactivity of mononuclear zinc complexes. In addition, use of tripodal ligands having a single internal hydrogen-bond donor has enabled the isolation of a novel cadmium hydroxide complex and examination of its CO2 chemistry, as well as the identification of a novel amide cleavage reaction which proceeds by initial formation of a deprotonated amide intermediate.