DICP OpenIR
Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity
Li, Dongmei1,2; Wang, Yong1; Yang, Chuanlu3; Han, Keli1
刊名DALTON TRANSACTIONS
2009
DOI10.1039/b810767j
2页:291-297
收录类别SCI
文章类型Article
WOS标题词Science & Technology ; Physical Sciences
类目[WOS]Chemistry, Inorganic & Nuclear
研究领域[WOS]Chemistry
关键词[WOS]C-H HYDROXYLATION ; ISOTOPE EFFECT PROFILES ; DENSITY-FUNCTIONAL THERMOCHEMISTRY ; SUBSTITUTED N,N-DIMETHYLANILINES ; ALKANE HYDROXYLATION ; ELECTRONIC-STRUCTURE ; REACTIVITY PATTERNS ; 2-STATE REACTIVITY ; REBOUND STEP ; COMPOUND-I
英文摘要The mechanism of N-dealkylation of N-cyclopropyl-N-methylaniline (3) catalyzed by cytochrome P450 (P450) was investigated using density functional theory. This reaction involves two steps. The first one is a C(alpha)-H hydroxylation on the N-substituent to form a carbinolaniline complex, and the second is a decomposition of the carbinolaniline to yield cyclopropanone (or formaldehyde) and N-methylaniline (or N-cyclopropylaniline). Our calculations demonstrate that the first step proceeds in a spin-selective mechanism (SSM), mostly on the low-spin (LS) doublet state. The rate-limiting C(alpha)-H activation is an isotope-sensitive hydrogen atom transfer (HAT) step. The environmental effect switches the regioselectivity of this reaction from a competition between N-decyclopropylation and N-demethylation to a clear preference for N-demethylation. This preference is consistent with former experimental studies. However, it is not in accord with the normal Delta E-BDE correlation since the BDE of C(alpha)-H on the methyl group is higher than that on the cyclopropyl group. Insight into the origin of the preference for N-demethylation reveals that tertiary amine 3 is different from normal hydrocarbons, possessing a unique pi(Ph)-pi(C-N) conjugated system. The electron delocalization effect of the pi(Ph)-pi(C-N) conjugated system in 3 makes the transition state pose a polar character, and the bulk polarity and hydrogen bonding capability of the protein pocket can exert a remarkable effect on the regioselectivity of N-dealkylation of 3. Decomposition of carbinolaniline is a water-assisted proton-transfer process in the nonenzymatic environment. The ring-intact cyclopropanone formed in the reaction sheds some light on the inability of 3 to inactivate P450 during its N-decyclopropylation.
语种英语
WOS记录号WOS:000261807400010
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/141352
专题中国科学院大连化学物理研究所
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China
3.Ludong Univ, Dept Phys, Yantai 264025, Peoples R China
推荐引用方式
GB/T 7714
Li, Dongmei,Wang, Yong,Yang, Chuanlu,et al. Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity[J]. DALTON TRANSACTIONS,2009(2):291-297.
APA Li, Dongmei,Wang, Yong,Yang, Chuanlu,&Han, Keli.(2009).Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity.DALTON TRANSACTIONS(2),291-297.
MLA Li, Dongmei,et al."Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity".DALTON TRANSACTIONS .2(2009):291-297.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Yang, Chuanlu]的文章
百度学术
百度学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Yang, Chuanlu]的文章
必应学术
必应学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Yang, Chuanlu]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。