Oxygenolysis of a series of copper(II)-flavonolate adducts varying the electronic factors on supporting ligands as a mimic of quercetin 2,4-dioxygenase-like activity.

Four copper(II)-flavonolate compounds of type [Cu(L R )(fla)] {where L R = 2-( p -R-benzyl(dipyridin-2-ylmethyl)amino)acetate; R = -OMe (1), -H (2), -Cl (3) and -NO 2 (4)} have been developed as a structural and functional enzyme-substrate (ES) model of the Cu 2+ -containing quercetin 2,4-dioxygenase enzyme. The ES model complexes 1-4 are synthesized by reacting 3-hydroxyflavone in the presence of a base with the respective acetate-bound copper(II) complexes, [Cu(L R )(OAc)]. In the presence of dioxygen the ES model complexes undergo enzyme-type oxygenolysis of flavonolate (dioxygenase type bond cleavage reaction) at 80 °C in DMF. The reactivity shows a substituent group dependent order as -OMe (1) > -H (2) > -Cl (3) > -NO 2 (4). Experimental and theoretical studies suggest a single-electron transfer (SET) from flavonolate to dioxygen, rather than valence tautomerism {[Cu II (fla - )] ↔ [Cu I (fla˙)]}, to generate the reactive flavonoxy radical (fla˙) that reacts further with the superoxide radical to bring about the oxygenative ring opening reaction. The SET pathway has been further verified by studying the dioxygenation reaction with a redox-inactive Zn 2+ complex, [Zn(L OMe )(fla)] (5).