A series of NiII-flavonolate complexes as structural and functional ES (enzyme-substrate) models of the NiII-containing quercetin 2,3-dioxygenase

Abstract

Ni^II-flavonolate complexes [Ni^IIL^R(fla)] (L^RH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}-p/m-R-benzoic acid, R: p-OMe (1), p-Me (2), m-Br (4) and m-NO₂ (5), fla: flavonolate) were synthesized and characterized with relevance to structural and functional models for the ES (enzyme–substrate) adduct of the Ni^II-containing quercetin 2,3-dioxygenase (2,3-QD). Their structures, spectroscopic features, redox properties and the reactivity toward molecular oxygen have been investigated. The complexes show a similar distorted octahedral structure and higher enzyme-type dioxygenation reactivity than other reported metal-flavonolate complexes in the oxidative O-heterocyclic ring-opening of the bound substrate flavonolate at lower temperature owing to the introduced carboxylate group in the supporting model ligands. The reaction rate shows first-order dependence on both of the complex and O₂ and the second-order rate constant k fits a Hammett linear free energy relationship (ρ = −0.71) for the substituent group in the supporting model ligand L^R. The complexes exhibit substituent group dependent structures, properties and reactivity and there are some relationship among them, which could be ascribed to the electronic nature of the substituent group via the benzoate, Ni^II ion and O(4)C(27)–C(21)C(22) “electron conduit”. In a word, the stronger electron donating group could induce a smaller torsion angle, larger λ_max and lower redox potential of the bound flavonolate, making a higher reactivity finally. This study is the first example of a series of structural and functional ES models of the Ni^II-containing 2,3-QD, providing important insights into the structure–property–reactivity relationship, the electronic substituent effects and carboxylate effects on the enzymatic reactivity and the catalytic role of the Ni^II-containing 2,3-QD.