Moles Pamela, Oliva Mónica, Safont Vicent S
Departament de Ciències Experimentals, Universitat Jaume I, Castelló, Spain.
J Phys Chem A. 2006 Jun 8;110(22):7144-58. doi: 10.1021/jp0574089.
A theoretical study on artemisinin decomposition mechanisms is reported. The calculations have been done at the HF/3-21G and B3LYP/6-31G(d,p) theoretical levels, by using 6,7,8-trioxybicyclo[3.2.2]nonane as the molecular model for artemisinin, and a hydrogen atom, modeling the single electron transfer from heme or Fe(II) in the highly acidic parasite's food vacuole, as inductor of the initial peroxide bond cleavage. All relevant stationary points have been characterized, and the appearance of the final products can be explained in a satisfactory way. Several intermediates and radicals have been found as relatively stable species, thus giving support to the current hypothesis that some of these species can be responsible for the antimalarial action of artemisinin and its derivatives.
报道了一项关于青蒿素分解机制的理论研究。计算是在HF/3 - 21G和B3LYP/6 - 31G(d,p)理论水平上进行的，使用6,7,8 - 三氧杂双环[3.2.2]壬烷作为青蒿素的分子模型，并以一个氢原子模拟来自血红素或处于高酸性疟原虫食物泡中的Fe(II)的单电子转移，作为初始过氧化物键断裂的引发剂。所有相关的驻点都已被表征，并且最终产物的出现能够以令人满意的方式得到解释。已发现几种中间体和自由基是相对稳定的物种，从而支持了当前的假说，即这些物种中的一些可能是青蒿素及其衍生物抗疟作用的原因。
