Biomimetic Study On Dioxygen Activation By Quercetin2,3-dioxygenase

The selective oxidations of the aromatic compounds with the C-C bond cleavage by molecular oxygen have long fascinated chemists and these chemically challenging,"green"-reactions have great potential application. Quercetin2,3-Dioxygenase (2,3-QD) could activate molecular oxygen to catalyze the oxygenative ring-opening reaction of flavonol with two C-C bond cleavage and release CO selectively and effectively at mild conditions, so the biomimetic study of quercetin2,3-dioxygenase has been received considerable attention recently. In order to get insights into the effects of metal ion, carboxylate group as well as the electronic substituent group of the model ligand on the structure, propertywreactivity of2,3-QD, the structure-function relationship of2,3-QD, the catalytic mechanism of2,3-QD, and the activation mechanism of dioxygen, herein we report a series of works as follows:1. Two new3N-1-COOH (mimicking the3His-1Glu active site of2,3-QD) model ligands LOMeH (2-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-4-methoxy-benzoic acid) and LNO2H (2-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-5-nitro-benzoic acid) have been designed, synthesized and characterized.2. A series of structural and functional2,3-QD model complexes [MⅡLOMe(OAc)](M: Mn, Fe, Co, Ni, Cu) and2,3-QD enzyme-substrate (ES) model complexes [MⅡLR(fla)](M: Mn, Fe, Co, Ni, Cu; R:OMe, Me, H, Br, NO2) are designed, synthesized and characterized. Their structures, spectroscopic features and redox properties have been investigated in detail.3. Detailed kinetic study on the reactions of the model complexes with substrate flavonol and molecular oxygen have been examined by monitoring the reactions with UV-vis. The qualitative and quantitative analysis of the reaction products have been examined by LC-MS and HPLC, respectively. Our model complexes have higher enzyme-like reactivity, which are good structural and functional models of2,3-QD. Based on these studies, the effects of metal ion, carboxylate group as well as the electronic substituent group of the model ligand on the structure, property and reactivity of2,3-QD, the structure-property-fuction relationship of2,3-QD, the catalytic mechanism of2,3-QD, and the activation mechanism of dioxygen have been discussed in detail. (1) Carboxylate effects:the model complexes [MⅡLOMe(OAc)](M:Mn, Fe, Co, Ni, Cu) and [MⅡLR(fla)](M:Mn, Fe, Co, Ni, Cu; R:OMe, Me, H, Br, NO2) all exhibit higher enzyme-like reactivity at lower temperature (30～100℃), due to the existing carboxylate group in the supporting model ligand, indicating that the carboxylate group of Glu is really a catalytic site of2,3-QD.(2) Metal ion effects:with the same ligand, although the structures of the model complexes are similar, their reactivity is different. The metal ion can affect the electron density of the bound flavonolate molecule, leading to different reactivity, which could provide some evidence for the variability in metal cofactor selectivity of2,3-QD.(3) Electronic effects of model ligand:with the same metal ion, although the structures of the model complexes are similar, their reactivity is different. The Hammett plots are all linear (p:-0.75～-0.71), so the rate-determining step of the reaction is a electrophilic reaction, which could provide some evidence for the role of second coordination sphere of2,3-QD.4. Based on the comparison of the structure, property and reactivity of the model complexes, the relationship of them has been discussed. The stronger electron donating group in the model ligand, the smaller torsion angle between B and C ring of flavonolate, the larger λmax of the π-> π*transition of the coordinated flavonolate, the lower redox potential of flavonolate, and the higher reactivity. The substituent group in the supporting model ligands could influence the reactivity of the complexes through the "electron conduit" confirmed by the coordinated benzoate, metal ion and O(4)=C(27)-C(21)=C(22) in the bound flavonolate, leading to different reactivity of the model complexes, which could provide some evidence for the structure-function relationship of2,3-QD.5. On the basis of above research, the mechanism of the reaction of flavonol and dioxygen catalyzed by [MⅡLOMe(OAc)] and dioxygenation reaction of [M1ILR(fla)] has been proposed. Although the mechanism is different from each other, the rate-determining step of each complex is the same, which is the single electron transfer from bound flavonolate to the oxygen molecule, forming fla· and O2·-. The structures of our model complexes are closer to the active site structure of the native2,3-QD, and our model complexes all exhibit higher enzyme-like reactivity. Thus our model complexes are the best structural and functional models of2,3-QD so far.