Flavonol dioxygenation catalysed by cobalt(II) complexes supported with 3N(COO) and 4N donor ligands: a comparative study to assess the carboxylate effects on quercetin 2,4-dioxygenase-like reactivity.

Two new cobalt(II)-acetato complexes, [Co II (L 3NCOO )(OAc)]·0.5H 2 O (1OAc·0.5H2O) and [Co II (L 4N )(OAc)](PF 6 ) (2OAc(PF6)), were synthesised using ligands L 3NCOO- (Li + L 3NCOO- = lithium 2-(benzyl((6'-methyl-[2,2'-bipyridin]-6-yl)methyl)amino)acetate) and L 4N ( N -benzyl-1-(6'-methyl-[2,2'-bipyridin]-6-yl)- N -(pyridin-2-ylmethyl)methanamine), respectively, to mimic the functional activity of cobalt(II)-quercetin-2,4-dioxygenase (Co II -2,4-QD). Additionally, Co(II)-flavonolato ternary complexes, [Co II (L 3NCOO )(fla)]·H 2 O (1fla·H2O) and [Co II (L 4N )(fla)](PF 6 ) (2fla(PF6)), were synthesised as enzyme-substrate models. All four complexes were thoroughly characterised by elemental analyses and spectroscopic methods. Structural characterisation was performed for 1OAc·0.5H2O, 2OAc(PF6)·CH2Cl2 and 2fla+ with a perchlorate counter anion, 2fla(ClO4)·1.5H2O. Furthermore, density functional theory (DFT) calculations, time-dependent DFT (TD-DFT) and molecular orbital (MO) analysis were performed for the flavonolato adducts 1fla and 2fla+. The catalytic activities of complexes 1OAc·0.5H2O and 2OAc(PF6) in the oxygenative degradation of flavonol (multiple-turnover reactions) were investigated at 70 °C in DMF to determine the effect of the carboxylate substituent over a pyridyl donor residue on reactivity. Complex 1OAc·0.5H2O showed a higher catalytic rate than complex 2OAc(PF6). The same reactivity order was observed for single-turnover dioxygenation reactions with ternary complexes (1fla > 2fla+). The formation constants ( K f ) of 1fla and 2fla+ species are comparable, implying that catalyst-substrate adduct formation occurs in similar amounts for both catalytic reactions. Therefore, the K f values have a similar impact on reactivities. However, the oxidation potential of the bound fla - /fla˙ couple in 1fla is considerably lower than that in 2fla+. DFT calculations predicted that the negatively charged carboxylate group of ligand L 3NCOO- determines the higher reactivity of 1fla with dioxygen by decreasing the oxidation potential of the bound fla - /fla˙ couple. During the dioxygenation process, the reactive Co(II)-bound flavonoxy radical was generated via single-electron transfer from the coordinated fla - to dioxygen, simultaneously forming a superoxide ion. The anionic carboxylate group improves the stability of the bound flavonoxy radical by providing substantial electron density to the electron-deficient fla˙ through the Co(II) centre, allowing the reactive fla˙ species to accumulate at an optimal concentration for effective catalysis. EPR spectroscopy successfully detected the cobalt-bound fla˙ species formed through the dioxygenation of 1fla. NBT 2+ and EPR spin-trapping experiments confirmed superoxide formation during the dioxygenation process. So, the present work describes Co II -2,4-QD model studies and clarifies the function of carboxylate in quercetinase-like reactivity.