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Catalytic Zinc Complexes for Phosphate Diester Hydrolysis
Author(s) -
Tirel Emmanuel Y.,
Bellamy Zoë,
Adams Harry,
Lebrun Vincent,
Duarte Fernanda,
Williams Nicholas H.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201400335
Subject(s) - chemistry , nucleophile , catalysis , reactivity (psychology) , ligand (biochemistry) , combinatorial chemistry , biocatalysis , hydrolysis , aldehyde , lewis acids and bases , zinc , metal ions in aqueous solution , reaction mechanism , organic chemistry , metal , medicine , biochemistry , receptor , alternative medicine , pathology
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.