title: Catalytic zinc complexes for phosphate diester hydrolysis.
abstract: Creating efficient artificial catalysts that can compete with biocatalysis has been an enduring challenge which has yet to be met. Reported herein is the synthesis and characterization of a series of zinc complexes designed to catalyze the hydrolysis of phosphate diesters. By introducing a hydrated aldehyde into the ligand we achieve turnover for DNA-like substrates which, combined with ligand methylation, increases reactivity by two orders of magnitude. In contrast to current orthodoxy and mechanistic explanations, we propose a mechanism where the nucleophile is not coordinated to the metal ion, but involves a tautomer with a more effective Lewis acid and more reactive nucleophile. This data suggests a new strategy for creating more efficient metal ion based catalysts, and highlights a possible mode of action for metalloenzymes.
authors.affiliation: Department of Chemistry, Sheffield University, Sheffield (UK).
authors.forename: Emmanuel Y
authors.initials: EY
authors.lastname: Tirel
authors.forename: Zoë
authors.initials: Z
authors.lastname: Bellamy
authors.forename: Harry
authors.initials: H
authors.lastname: Adams
authors.forename: Vincent
authors.initials: V
authors.lastname: Lebrun
authors.forename: Fernanda
authors.initials: F
authors.lastname: Duarte
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Williams
mesh_terms: D002384:Catalysis; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D006868:Hydrolysis; D008745:Methylation; D010710:Phosphates / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D004952:Esters; D010710:Phosphates; D015032:Zinc
keywords: DNA cleavage; bioinorganic chemistry; enzyme models; kinetics; zinc