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(II)L(R)(fla)] (L(R)H: 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.

Bioinspired Trispyrazolylborato Nickel(II) Flavonolate Complexes and Their Reactivity Toward Dioxygen

“…A DMF solution of compound 1 in an argon atmosphere at room temperature exhibits an intense absorption band at λ = 436 nm ( ε = 11.79 mM –1 · cm –1 ) which can be assigned to the π→π* transition of the coordinated flavonolate. Its position is comparable to bands displayed by other Ni II Fla complexes reported in literature . Unfortunately, when argon was exchanged by O 2 under these conditions, complex 1 proved unreactive towards dioxygen.…”

Quercetin 2,4‐Dioxygenase Activates Dioxygen in a Side‐On O2–Ni Complex

“…[4] However,h ow QueDs activate dioxygen is still under debate:either dioxygen reacts directly with QUE, and the metal ion just stabilizes the more reactive anionic form of QUE, or dioxygen is activated by binding to the active-site metal ion. [3,5] Mechanisms without direct binding of dioxygen to nickel are appealing for several reasons:QUE can react spontaneously with O 2 ,thus making O 2 activation at am etal site dispensable; [6] inorganic model catalysts that catalyze the breakdown of QUEwith O 2 require no open coordination site at the metal; [7] cofactor-independent dioxygenases [8] can cleave heteroaromatic rings with dioxygen in the absence of metal ions;a nd the presence of different metal ions in the various QueDs suggests that the individual properties of the metals are not essential for catalysis. [3] We investigated QueD from Streptomyces sp.strain FLA (QueD FLA ), which differs from the structurally characterized bicupin QueDs by its monocupin fold and type of active-site metal.…”

Structures of rhenium(I) complexes with 3-hydroxyflavone and benzhydroxamic acid as O,O′-bidentate ligands and confirmation of π-stacking by solid-state NMR spectroscopy

“…This could be due to the small O4-Re1-O5 bite angle of 76.72 (9) . All the bond lengths and angles are in the normal ranges compared to similar compounds (Speier et al, 1990;Balogh-Hergovich et al, 1991;Sun et al, 2014;Annan et al, 1990;Schutte et al, 2011Schutte et al, , 2012Mokolokolo et al, 2017;Manicum et al, 2015Manicum et al, , 2018Twala et al, 2015). The ReÁ Á ÁRe nonbonding distance is 5.114 (7) Å .…”