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.

Enhancing Phosphate Diester Cleavage by a Zinc Complex through Controlling Nucleophile Coordination

“…Very recently, we reported the properties of a ligand that incorporated an acetal hydrate, 2 . The acetal hydrate allowed turnover and provided unexpectedly enhanced reactivity, which we proposed was due to the involvement of a non‐metal‐ion‐bound nucleophile 15. Following this line of enquiry, we sought ways of introducing a nucleophile into the ligand structure in a geometry that would prevent coordination to the metal centre to avoid reducing its nucleophilicity.…”

“… pH Rate profile for the cleavage of BNPP; cleavage catalysed by 1 (▪)15 and 2 (▴);15 cleavage catalysed by 3 (•) at 25 °C ([buffer]=0.05 M , I =0.1 M (NaNO 3 )). Solid lines are from fitting Equation (1) to the data.…”

A Bis‐Zn2+‐Pyridyl‐Salen‐Type Complex Conjugated to the ATP Aptamer: An ATPase‐Mimicking Nucleoapzyme

“…In addition, polyamine macrocycles were used as catalytic receptors for hydrolyzing ATP to ADP and phosphate through the electrostatic binding of ATP to partially protonated amine groups of the receptor and the concomitant activation of the phosphate ester linkages through the formation of phosphoamidate intermediates . Furthermore, the significance of cooperative di‐metal‐ion activation (Zn 2+ ) of the phosphodiester linkage of ATP towards hydrolysis has previously been reported …”

Enantioselective hydrolysis of amino acid esters by non-chiral copper complexes equipped with bis (β-cyclodextrin)s

“…Biomimetic study could help understand the origins of efficiency and specificity of enzymes [5,6]. Introducing supramolecules as the second coordination sphere brings multiple non-covalent interactions to regulate the nature of the metal ion, which was proved to be a promising approach [7][8][9][10][11].…”