Quantum mechanics study on synthetic model of copper-containing quercetin 2,4-dioxygenase.

We report a computational study on the dioxygenation reaction of the substrate flavonolate (fla) by a synthetic model complex [Cu 2+ (idpa)(fla − )] + (idpa = 3,3′-iminobis( N , N -dimethylpropylamine) and related species mimicking quercetin 2,4-dioxygenases. It is found that the reaction mechanism obtained for the present biomimetic complexes is substantially different from the plausible enzymatic reaction. All model complexes favor a single electron transfer from flavonolate to dioxygen over a valence tautomerism [Cu 2+ (idpa)(fla − ) ↔ Cu + (idpa)(fla )], and a subsequent intersystem crossing and a ring-closure lead to a formation of a 1,2-dioxetane intermediate instead of undergoing a direct formation of a precursor endoperoxide. The generation of the 1,2-dioxetane intermediate is shown to be the rate-determining step and inclusion of a carboxylate co-ligand can enhance the reactivity, rendering this process barrier-free. We have also proposed for the first time a pathway, which can circumvent a non-enzymatic reaction by involving conversion from the 1,2-dioxetane to the endoperoxide with lower barriers. [ABSTRACT FROM AUTHOR]