磷酸酯类反应性物质是乙酰胆碱酯酶不可逆抑制剂。本文应用概念密度泛函理论(CDFT)，采用四组条件(B3LYP/6-311++G(2d, 3p)/gas，B3LYP/6-311++G(2d, 3p)/CPCM/water，MP2/6-311++G(2d, 3p)/gas，MP2/6-311++ G(2d, 3p)/CPCM/water)，对20多个磷酸酯反应性物质进行反应性描述指数计算，包括分子的化学势μ，绝对硬度η、亲电性指数ω、分子的前线轨道能量等分子整体描述参数，以及原子福井函数、自然键轨道(NBO)电荷、Wiberg键级、NBO键级等分子局域描述参数。通过对反应性描述指数以及定量构性关系(QSPR)方程预测结果的比较分析，得出结论：大多数化合物亲电进攻的反应中心发生在磷原子上；磷酸酯类化合物侧链乙胺基叔氮的质子化，将显著增强反应中心磷原子的亲电进攻能力；B3LYP/6-311++G(2d, 3p)/gas为最合理的计算条件；应用反应性描述指数建立的QSPR模型明显优于常规的2D-QSPR模型，能够用于乙酰胆碱酯酶不可逆抑制剂的精确毒性预测。
Following the exceptional success of density functional theory (DFT) in the realm of quantum chemistry, the conceptual DFT (CDFT) method has been widely used for describing the dynamic reactivity index of reactive chemicals in recent years. Reactive chemicals refer to those that bind covalently to biological macromolecules; in other words, the binding of the ligand with the receptor or enzyme involved with the breakage of the old bond and the process of formation of the new bond. Organophosphorus AChE irreversible inhibitors are reactive chemicals. In the present work, we calculated the reactivity descriptors for AChE irreversible inhibitors (organophosphate compounds), including some pesticides and chemical warfare agents, by the CDFT method at the B3LYP/6-311++G(2d, 3p)/gas, B3LYP/6-311++G(2d, 3p)/CPCM/water, MP2/6-311++G(2d, 3p)/gas, MP2/6-311++G(2d, 3p)/CPCM/water levels, in order to analyze their reactivity and determine the optimal parameters for calculation. Reactivity descriptors such as chemical potential (μ), vertical ionization energy (I), vertical electronic affinity (A), molecular absolute hardness (η), electrophilicity (ω), condensed atomic Fukui function, and varied natural bond orbital (NBO) bond order, were used to identify changes in the reactivity of these compounds in the gas and aqueous phases with the conductor-like polarizable continuum model (CPCM) model. The values of the reactivity descriptors and quantitative structure-property relationship (QSPR) models indicated that: the center of the phosphor atom (P) was the nucleophilic reaction site with AChE for most of selected compounds; substituted tertiaryamine protonization in organophosphorus compounds greatly enhanced the electrophilic attackingability of the P reaction center; and as a whole, conformation did not have a significant effect on the reactivity for theDFT/B3LYP method, with an exception for the MP2 method which showed a comparative instability in results. The initial QSPR model in training sets of pLD50 with stepwise regression analysis shows that the B3LYP/6-311++G(2d, 3p)/gas level can