细胞色素P450催化4-氯-N-环丙基-N-异丙基苯胺Cα–H羟基化反应机理的理论研究

采用密度泛函理论的B3LYP方法,研究了细胞色素P450催化4-氯-N-环丙基-N-异丙基苯胺Cα–H羟基化的反应机理.该反应包含环丙基的羟基化和异丙基的羟基化两个反应途径,且这两个反应路径都是包含氢原子传递的协同过程,二重态的能垒明显低于四重态,反应主要在二重态上进行.通过比较这两个反应路径中Cα–H羟基化反应的活化能,推算出4-氯-N-环丙基-N-异丙基苯胺中环丙基Cα–H羟基化与异丙基Cα–H羟基化的反应速率之比为1.8：1,进而推测出该底物在P450催化下脱环丙基和脱异丙基反应的分支比为64%：36%.这与实验结果一致....

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Bibliographic Details
Published in催化学报 Vol. 32; no. 7; pp. 1208 - 1213
Main Author 李冬梅 刘建勇
Format Journal Article
LanguageChinese
Published 2011
Subjects
反应机理
反应速率
密度泛函理论
氢原子传递
能垒
过渡态
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Summary:采用密度泛函理论的B3LYP方法,研究了细胞色素P450催化4-氯-N-环丙基-N-异丙基苯胺Cα–H羟基化的反应机理.该反应包含环丙基的羟基化和异丙基的羟基化两个反应途径,且这两个反应路径都是包含氢原子传递的协同过程,二重态的能垒明显低于四重态,反应主要在二重态上进行.通过比较这两个反应路径中Cα–H羟基化反应的活化能,推算出4-氯-N-环丙基-N-异丙基苯胺中环丙基Cα–H羟基化与异丙基Cα–H羟基化的反应速率之比为1.8：1,进而推测出该底物在P450催化下脱环丙基和脱异丙基反应的分支比为64%：36%.这与实验结果一致.
Bibliography:density functional theory; transition state; hydrogen atom transfer; energy barrier; reaction rate; reaction mechanism
The reaction mechanism of Cα–H hydroxylation of 4-chloro-N-cyclopropyl-N-isopropylaniline catalyzed by cytochrome P450 was investigated using the density functional theory. The Becke＇s three-parameter hybrid exchange functional and the Lee-Yang-Parr correlation functional（B3LYP） were used in the structure optimization and single-point energy calculations. There are two Cα–H hydroxylation reaction pathways for 4-chloro-N-cyclopropyl-N-isopropylaniline catalyzed by P450. One is Cα–H hydroxylation at the cyclopropyl group,and the other is Cα–H hydroxylation at the isopropyl group. Our calculations demonstrate that the Cα–H activation at both the cyclopropyl group and the isopropyl group is a hydrogen atom transfer process,and the reaction is concerted. Since the Cα–H activation energy on the high-spin quartet state is much higher than that on the low-spin（LS） doublet state,the Cα–H hydroxylation
ISSN:0253-9837
1872-2067