DFT study on the radical anions formed by primaquine and its derivatives.
DFT study on the radical anions formed by primaquine and its derivatives.
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DOI：
10.1021/tx200094v
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发表时间：
2011-09-19
影响因子：
4.1
通讯作者：
Doerksen RJ
中科院分区：
文献类型：
--
作者：
Liu H;Walker LA;Doerksen RJ
采用密度泛函理论方法研究了 8-氨基喹啉抗疟药伯氨喹及其几种代谢物的电子亲和力 (EA)。我们首先考虑了 5 位上的六个取代基：-CH3、-OH、-OCH3、-Ph、-OPh 和 -CHO。我们发现，在气相中，绝热 EA 与母体伯氨喹的 -CH3、-OH 和 -OCH3 取代基相似。相反，-Ph、-OPh 和 -CHO 取代基均显着增加绝热 EA。然而，由于相对于母体伯氨喹具有显着的正垂直 EA，预计只有 -CHO 取代的化合物会在气相中形成稳定的共价结合自由基阴离子。另外，当8位被N-羟基取代或形成醌-亚胺结构时，电子捕获能力显着增加。在水溶液中，所有这些分子都具有比气相中大得多的绝热 EA。此外，所有垂直 EA 在水溶液中均呈阳性。进一步讨论了这些发现对我们对 8-氨基喹啉化合物红细胞毒性的机制理解的影响。
The electron affinities (EA) of the 8-aminoquinoline antimalarial drug primaquine and several of its metabolites were studied using the density functional theory method. We first considered six substituents at the 5-position, −CH3, −OH, −OCH3, −Ph, −OPh and −CHO. We found that in the gas phase the adiabatic EAs are similar to that of the parent primaquine for the −CH3, −OH and −OCH3 substituents. In contrast, the −Ph, −OPh and −CHO substituents all markedly increase the adiabatic EA. However, only the −CHO substituted compound is predicted to form a stable covalently bound radical anion in the gas phase due to its significant positive vertical EA relative to that of the parent primaquine. In addition, when the 8-position is substituted by the N-hydroxyl group or a quinone-imine structure is formed, the electron capture ability is significantly increased. In aqueous solution, all these molecules have significantly larger adiabatic EAs than in the gas phase. In addition, all the vertical EAs are positive in aqueous solution. The implications of these findings for contributing to our mechanistic understanding of the red cell toxicity of 8-aminoquinoline compounds are further discussed.
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影响因子：
2.9
作者：
Gu, Jiande;Xie, Yaoming;Schaefer, Henry F., III
通讯作者：
Schaefer, Henry F., III
影响因子：
3.3
作者：
Lind, Maria C.;Richardson, Nancy A.;Schaefer, Henry F., III
通讯作者：
Schaefer, Henry F., III
影响因子：
15
作者：
Gu, JD;Xie, YM;Schaefer, HF
通讯作者：
Schaefer, HF
影响因子：
4.4
作者：
BECKE, AD
通讯作者：
BECKE, AD
影响因子：
15
作者：
Gu, JD;Xie, YM;Schaefer, HF
通讯作者：
Schaefer, HF