Biomimetic Studies For Different Active Site Of The Non-heme Iron Dioxygenase

Design and synthesis of structural and functional model complexes of the native enzyme to explore the structure-function relationship of the enzyme, the reaction mechanism of the enzyme as well as the activation mechanism of molecular oxygen have received considerable attention recently. In order to get insights into the different active site model ligands and electronic effects of the substituent group of the model ligands and substrates on the dioxygenation reactivity for the active site of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and ?-diketone dioxygenase (Dke1) model complexes, herein we report a series of works as follows:(1) Three new 2His-1COO series model ligands L2NORH (2-{[(Benzyl-pyridin-2-ylmethyl)amino]methyl}-4/5-R-benzoic acid; R:4-OMe,4-Me,5-Br) have been designed, synthesized and characterized.(2) A series of the Fe? and Co? ES (enzyme-substrate) model complexes with them and ligand L2NONO2H and 3His-1COO series model ligands L3NORH (2-{[Bis(pyridine-2-ylmethyl)amino]methyl}-4/5-R-benzoic acid R:4-OMe,4-Me,5-Br,5-NO2), and a serial substrates PPR (p-R-phenylpyuvic acid, R:OH, Me, H, Br, NO2) (common substrate of HPPD and Dke1) have also been synthesized and characterized.(3) The reactivity of the model complexes towards molecular oxygen have been investigated by monitoring the absorption changes of the model complexes with UV-vis, and the qualitative and quantitative reaction products analysis were also examined in detail by LC-MS and HPLC. The effects of different active sites, electronic effect of the ligands and substrates on the structure, properties and reactivity have also been investigated. On the basis of the spectroscopic, redox property, kinetic and products analysis results, we have been proposed the Dkel-type dioxygenation reaction mechanism of the model complexes.The results of the reactivity of the model complexes towards molecular oxygen are as follows:? All 2His-1COO and 3His-1COO series model complexes can react with dioxygen to degrade the bound substrate PPR to give the Dke1 type product p-R-benzaldehyde (R:OH, Me, H, Br, NO2) as main products. For different active site model complexes, the yields of 2His-1COO series are higher than 3His-1COO series;? For the same active site and substrate, different substituent groups of ligands, the stronger electron-withdrawing ability, the higher reactivity;? For the same active site and ligand, different substituent groups of substrates, the stronger electron-withdrawing ability, the higher reactivity.In a word, the rate-determining step is the step that the superoxyl radiacl anion necleophilic attack the C2 of HPP to form the peroxo species, so the reaction of the model complexes with dioxygen is a necleophilic reaction.