Kinetics and mechanism of the Cu(I) and Cu(II) flavonolate-catalyzed oxygenation of flavonol.: Functional quercetin 2,3-dioxygenase models

The oxygenation of flavonol (flaH) using Cu-II(fla)(2) and Cu-I(fla)(PPh3)(2) catalysts results in oxidative cleavage of the heterocyclic ring to give O-benzoylsalicylic acid (O-bsH) and CO as primary products. The oxygenolysis of flavonol catalyzed by Cu-II(fla)(2) in DMF was followed by electronic spectroscopy and the rate law was found to be - d[flaH]/dt = k(obs)[flaH][Cu-II(fla)(2)][O-2]. The rate constant, activation energy, activation enthalpy and entropy at 393 K are as follows: k(obs)/s(-1) mol(-2) dm(-6) = (2.02 +/- 0.07) x 10(3), E-a/kJ mol(-1)= 142 +/- 6, Delta H double dagger/kJ mol(-1)= 139 +/- 5, and Delta S double dagger/J mol(-1) K-1 = 168 +/- 13. The results of the kinetic measurements of the Cu-I(fla)(PPh3)(2)-catalyzed oxygenation shows that in the presence of a large excess of the substrate, the Cu-I(fla)(PPh3)(2) reacts with flavonol in an irreversible step to Cu-II(fla)(2), and, then, the mechanism of the oxygenation is the same as that with the Cu-II(fla)(2)-catalyzed reaction. (C) 2000 Elsevier Science B.V. All rights reserved.