Copper(II)-flavonolate complexes of 2N ligands as functional models for quercetin 2,4-dioxygenase enzymes: The role of axially coordinated water and ligand substitution on dioxygenase activity

Three new copper(II)-flavonolate complexes of the type [Cu(L)(fla)(ClO4)] 1-3, where L is the 2N ligand N(pyridin-2-ylmethyl)aniline (L1), 2,6-dimethyl-N-(pyridin-2-ylmethyl)aniline (L2) and 2,6-diisopropyl-N-(pyridin-2-ylmethyl)aniline (L3), and H(fla) is 3-hydroxyflavonone, have been isolated as functional models for Cu (II)-containing quercetin 2,4-dioxygenase (2,4-QueD). Single crystal X-ray structure of 3 contains a CuN2O2O' chromophore with a slightly distorted square pyramidal geometry (TBDSP, & tau; = 0.03). The pyridyl N1 and the tertiary amine N2 nitrogens of the 2N ligand occupy the two corners of the basal plane. The O1 (enolate) and the carbonyl O2 atoms of deprotonated 3-hydroxyflavanone (fla- ) occupy the remaining corners while the O3 of perchlorate anion (ClO4- ) occupies the axial position at a longer distance. The molecular structures of the complexes 1-3, their aquated species [Cu(L)(fla)(H2O)]+ 1a-3a and the square planar species [Cu(L)(fla)]+ 1c-3c have been computed by using DFT method. While 1-3 contain axially coordinated perchlorate 1a-3a contain axially coordinated water molecule with a slightly distorted square pyramidal geometry (CuN2O2O') with varying trigonality (& tau;, 0.03-0.05). The significantly high g|| (2.305) and low A|| (150 x 10-4 cm-1) values observed for 1-3 are consistent with & pi;-back bonding of Cu(II) with the conjugated carbonyl group of coordinated fla- and are typical of type-II copper enzymes. The electrochemical reduction of CuII to CuI and oxidation of flaoccur upon dissociation of axially coordinated water molecule in 1a-3a formed in DMF solution to give 1c-3c. Upon exposure to dioxygen, all the Cu(II)-flavonolate adducts undergo oxygenative degradation in DMF solution, as seen from the disappearance of the LMCT band at 430 nm at 80 degrees C to produce CO and the corresponding acids. The rate of dioxygenation, kO2, of the complexes decrease in the order, 1 (3.31 & PLUSMN; 0.53) > 3 (2.59 & PLUSMN; 0.36) > 2 (1.52 & PLUSMN; 0.13 x 10-1 M-1 s- 1), due to electron-donating substituents on the primary ligand.