Flavonolate Complexes of MII (M = Mn, Fe, Co, Ni, Cu, and Zn). Structural and Functional Models for the ES (Enzyme-Substrate) Complex of Quercetin 2,3-Dioxygenase

A series of flavonolate complexes [(ML)-L-II(fla)] (M = Mn (1), Fe (2), Co (3), Ni (4), Cu (S), and Zn (6), LH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic acid, fla: flavonolate) have been synthesized as structural and functional models for the ES (enzyme substrate) complexes of the active site of various M-II-containing quercetin 2,3-dioxygenase (2,3-QD) and their structures, spectroscopic features, and redox properties, as well as the reactivity toward molecular oxygen, have been investigated. The metal centers of [(FeL)-L-II(fla)]center dot H2O (2), [(CoL)-L-II(fla)]center dot CH3OH (3), and [(NiL)-L-II(fla)] (4) exhibit a distorted octahedral geometry with two oxygen atoms of fla, one oxygen atom of the benzoate group of ligand L, and three nitrogen atoms of ligand L, in which oxygen atom of the carbonyl group of fla and one of the pyridine nitrogen atoms occupy the axial positions. The complexes [(ML)-L-II(fla)} exhibit relatively high reactivity in the oxidative ring-opening of the bound flavonolate at lower temperature, presumably due to the existing carboxylate group in the supporting ligand. Thus, our complexes act as good functional ES models of various metal(II)-containing 2,3-QD. In addition, complexes [(FeL)-L-II(fla)]center dot H2O (2), [(CoL)-L-II(fla)]center dot CH3OH (3), and [(NiL)-L-II(fla)] (4) are the first structurally characterized Fe-II-, Co-II-, and Ni-II-flavonolate complexes, as an active site ES model of Fe-II-, Co-II-, and Ni-II-containing 2,3-QD, respectively. The model complexes exhibit notably different reactivity in the order of Fe (2) > Cu (5) > Co (3) > Ni (4) > Zn (6) > Mn (1). The differences in the reactivity among them may be attributed to the redox potential of the coordinated flavonolate of the complexes, which are remarkably influenced by the Lewis acidity of the metal ion and its coordination environment. Our study is the first example of the metal ion effects on the enzyme-like dioxygenation reactivity, providing important insights into the metal ion effects on the enzymatic reactivity of various metal(11)-containing 2,3-QD.