Li Xiao-Xi, Postils Verònica, Sun Wei, Faponle Abayomi S, Solà Miquel, Wang Yong, Nam Wonwoo, de Visser Sam P
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical Physics (LICP), Chinese Academy of Sciences, Lanzhou, 730000, P. R. China.
Institut de Química Computacional i Catàlisi (IQCC) and Department de Química, Universitat de Girona, Campus de Montilivi, C/ Maria Aurèlia Capmany 6, 17003, Girona, Catalonia, Spain.
Chemistry. 2017 May 5;23(26):6406-6418. doi: 10.1002/chem.201700363. Epub 2017 Apr 20.
The cytochromes P450 are versatile enzymes in human physiology that perform substrate hydroxylation reactions extremely efficiently. In this work, we present results of a computational study on the reactivity patterns of Compound I, Compound II, and protonated Compound II with model substrates, and we address the question of which of these compounds is the most effective oxidant? All calculations, regardless of the substrate, implicated that Compound I is the superior oxidant of the three. However, Compound II and protonated Compound II were found to react with free energies of activation that are only a few kcal mol higher in energy than those obtained with Compound I. Therefore, Compound II and protonated Compound II should be able to react with aliphatic groups with moderate C-H bond strengths. We have analysed all results in detail and have given electronic, thermochemical, valence bond, and molecular orbital rationalizations on the reactivity differences and explained experimental product distributions. Overall, the findings implied that alternative oxidants could operate alongside Compound I in complex reaction mechanisms of enzymatic and synthetic iron porphyrinoid complexes.
细胞色素P450是人体生理学中功能多样的酶，能极其高效地进行底物羟基化反应。在这项工作中，我们展示了关于化合物I、化合物II和质子化化合物II与模型底物反应模式的计算研究结果，并探讨了这些化合物中哪一种是最有效的氧化剂这一问题。所有计算结果，无论底物如何，都表明化合物I是三者中更优越的氧化剂。然而，发现化合物II和质子化化合物II反应的活化自由能仅比化合物I的高几千卡·摩尔。因此，化合物II和质子化化合物II应该能够与具有中等C-H键强度的脂肪族基团发生反应。我们详细分析了所有结果，并对反应性差异给出了电子、热化学、价键和分子轨道方面的合理解释，同时解释了实验产物分布情况。总体而言，这些发现表明在酶促和合成铁卟啉类配合物的复杂反应机制中，替代氧化剂可能与化合物I共同起作用。
