Quantitative structure–activity relationship studies on ironporphyrin-catalyzed cyclohexane oxidation with PhIO

Abstract

Quantitative structure–activity relationship (QSAR) studies were performed on the ironporphyrin-catalyzed biomimetic oxidation of cyclohexane. Through quantum chemical calculations, the molecular structures of nine different ironporphyrin catalysts have been optimized and their respective quantum chemical descriptors (FMO energies E HOMO, E LUMO, FMO energy gap DEHL, partition coefficient log P) have been obtained. The ironporphyrin-catalyzed cyclohexane hydroxylation with PhIO was chosen as the model reaction. The yield of cyclohexanol (yield (%)) and the reaction rate constant (lg k) were obtained experimentally, and the reaction kinetics was studied accordingly. 2D-QSAR studies for ironporphyrin catalysts were performed by using multiple linear regression (MLR) analysis. From the established QSAR model equations of lg k, yield (%) and the quantum chemical descriptors (lg k = −1.433 + 0.009 log P − 0.406 E LUMO-b R = 0.968 and yield (%) = 9.556 + 0.500 log P − 8.997 E LUMO-b R = 0.821), we conclude that it is the frontier molecular orbital (FMO) energy level E LUMO-b which has the most significant effect on the catalytic activity of the ironporphyrins. Further molecular graphics studies and Mulliken's electron population analysis indicated that the energy level of E LUMO-b can be altered by introducing peripheral substituting groups on the meso-phenyl ring. Since the electron withdrawing substituents could lower E LUMO-b and disperse the electron density of around the centro-metal core of porphyrin better, they can facilitate ironporphyrin's binding with the oxidant and, consequently increase the catalytic activity of ironporphyrin. We also notice that the partition coefficient log P of ironporphyrin molecule affects the reaction rate and the yield of the cyclohexane hydroxylation reaction as well. Our study may be beneficial for future catalyst design for the metalloporphyrin-catalyzed hydrocarbon oxidations.