Effects of introduction of α-carboxylate, N-methyl, and N-formyl groups on intramolecular cyclization of o-quinone amines: Density functional theory-based study
Effects of introduction of α-carboxylate, N-methyl, and N-formyl groups on intramolecular cyclization of o-quinone amines: Density functional theory-based study
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DOI：
10.1002/qua.25445
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发表时间：
2017-12-05
影响因子：
2.2
通讯作者：
Kasai, Hideaki
中科院分区：
文献类型：
--
作者：
Kishida, Ryo;Saputro, Adhitya Gandaryus;Kasai, Hideaki
与各种生物过程相关的邻醌胺可以发生自发的分子内环化（氨基封端的烃侧链的闭环反应），从而使其失去活性以进行另一种可能的反应，即硫醇结合。采用基于密度泛函理论的计算，获得了各种邻醌胺（即多巴胺醌、多巴醌、N-甲基多巴胺醌、N-甲酰基多巴胺醌以及相应的亚甲基插入类似物）分子内环化中沿着C-N键形成的势能曲线。引入α-羧酸酯和N-甲基会降低活化势垒，而引入N-甲酰基则会增加活化势垒。指出了活化能垒与最高占据分子轨道能级之间的负相关关系。此外，插入亚甲基的类似物显示出降低的活化屏障。这是通过过渡态空间排斥力的减少来解释的。
o-Quinone amines, which are relevant to various biological processes, can undergo spontaneous intramolecular cyclization (ring closure reaction by amino-terminated hydrocarbon side chain) that deactivates them toward another possible reactions, that is, thiol binding. Density functional theory-based calculation is employed for obtaining the potential energy curves along the C-N bond formation in the intramolecular cyclization of various o-quinone amines, viz., dopaminequinone, dopaquinone, N-methyl-dopaminequinone, N-formyl-dopaminequinone, and the corresponding methylene-inserted analogues. The activation barrier is decreased by introduction of alpha-carboxylate and N-methyl group whereas increased by introduction of N-formyl group. A negative correlation between the activation barriers and the level of highest occupied molecular orbital is pointed out. Furthermore, the methylene-inserted analogues show decreased activation barriers. This is explained by reduction of steric repulsion in the transition state.