Estrogen Formation via H-Abstraction from the O鈥揌 Bond of gem-Diol by Compound I in the Reaction of CYP19A1: Mechanistic Scenario Derived from Multiscale QM/MM Calculations

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• 作者：Kai Xu ; Yong Wang ; Hajime Hirao
• 刊名：ACS Catalysis
• 出版年：2015
• 出版时间：July 2, 2015
• 年：2015
• 卷：5
• 期：7
• 页码：4175-4179
• 全文大小：358K
• ISSN：2155-5435

文摘

Recent experiments suggested that, contrary to traditional belief, the third step of aromatase-catalyzed estrogen formation should be effected by compound I (Cpd I), rather than by ferric peroxide. We performed QM/MM calculations to address the question of how Cpd I drives the aromatization process. Surprisingly, the calculations show that the reaction begins with hydrogen abstraction from the O鈥揌 bond of a gem-diol substrate, which is followed by barrierless homolytic C鈥揅 bond cleavage and then 1尾-H-abstraction. Proton-coupled electron transfer enables the cleavage of the strong O鈥揌 bond. Another product, carboxylic acid, can be formed from either the gem-diol or aldehyde.