Stereoelectronic properties of antimalarial artemisinin analogues in relation to neurotoxicity
Stereoelectronic properties of antimalarial artemisinin analogues in relation to neurotoxicity
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DOI：
10.1021/tx9802116
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发表时间：
1999-05-01
影响因子：
4.1
通讯作者：
Karle, JM
中科院分区：
文献类型：
--
作者：
Bhattacharjee, AK;Karle, JM
对青蒿素及其8种衍生物的分子电子结构进行了量子化学计算，得到了区分高、低神经毒性类似物的立体电子鉴别器。详细的从头算量子化学计算导致每个分子的几何形状的完全优化，随后使用3- 21 G * 分裂价基组计算它们的立体电子性质，并将立体电子性质与体外神经毒性进行比较。神经毒性最小的化合物具有更强的极性，电场远离内过氧化物键，并且在全含碳环C的货车德瓦尔斯表面上具有更高的正电势，对裂解更稳定的过氧化物键，内过氧化物的负静电电势较小，并且单个负电势区域延伸超出分子的货车德瓦尔斯表面。一般而言，较高的内在亲脂性与较大的神经毒性相关。
Quantum chemical calculations on the molecular electronic, structure of artemisinin (qinghaosu) and eight of its derivatives have resulted in stereoelectronic discriminators that differentiate between analogues with higher and lower neurotoxicities. Detailed ab initio quantum chemical calculations leading to complete optimization of geometry of each of the molecules were followed by calculation of their stereoelectronic properties using the 3-21G* split valence basis sets and comparison of the stereoelectronic properties to in vitro neurotoxicity. The least neurotoxic compounds are more polar with an electric field pointing away from the endoperoxide bond and have a higher positive potential on the van der Waals surface of the all carbon-containing ring C, a more stable peroxide bond to cleavage, a less negative electrostatic potential by the endoperoxide, and a single negative potential region extending beyond the van der Waals surface of the molecule. In general, higher intrinsic lipophilicity is associated with greater neurotoxicity.