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

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 EHOMO, ELUMO, 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 − 0.406ELUMO-bR = 0.968 and yield (%) = 9.556 + 0.500 log P − 8.997ELUMO-bR = 0.821), we conclude that it is the frontier molecular orbital (FMO) energy level ELUMO-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 ELUMO-b can be altered by introducing peripheral substituting groups on the meso-phenyl ring. Since the electron withdrawing substituents could lower ELUMO-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.

Graphical abstractQSAR studies had been applied to investigate the cyclohexane hydroxylation reaction catalyzed by nine ironporphyrin derivatives. The ironporphyrin molecular structures’ optimization and quantum chemical descriptors have been obtained based on quantum chemical calculations. Bi-parametric QSAR model equations for the rate constant lg k and cyclohexanol yield had been built separately by the MLR analysis.Figure optionsDownload full-size imageDownload as PowerPoint slide