Bhattacharjee A K, Karle J M
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Chem Res Toxicol. 1999 May;12(5):422-8. doi: 10.1021/tx9802116.
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.
对青蒿素（青蒿素）及其八种衍生物的分子电子结构进行的量子化学计算得出了立体电子判别指标，可区分具有较高和较低神经毒性的类似物。在通过详细的从头算量子化学计算实现每个分子几何结构的完全优化之后，使用3-21G分裂价基组计算其立体电子性质，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极性更大，电场指向远离内过氧化物键的方向，并且在所有含碳环C的范德华表面上具有更高的正电势，过氧化物键更稳定不易断裂，内过氧化物的负静电势更小，并且单个负电势区域延伸到分子的范德华表面之外。一般而言，较高的固有亲脂性与较大的神经毒性相关。
