Theoretical study of N-dealkylation of N-cyclopropyl-N-methylaniline catalyzed by cytochrome P450: insight into the origin of the regioselectivity
文献类型：期刊论文
| 作者 | Li, Dongmei1,2; Wang, Yong1; Yang, Chuanlu3; Han, Keli1 |
| 刊名 | dalton transactions
 |
| 出版日期 | 2009 |
| 期号 | 2页码:291-297 |
| 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. |
| 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 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000261807400010 |
| 公开日期 | 2015-11-17 |
| 源URL | [http://159.226.238.44/handle/321008/141352]  |
| 专题 | 大连化学物理研究所_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. |
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来源：大连化学物理研究所
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