Vijayalakshmi K Periya, Suresh Cherumuttathu H
Computational Modeling and Simulation Section, National Institute for Interdisciplinary Science and Technology (CSIR), Trivandrum 695019, India.
Org Biomol Chem. 2008 Dec 7;6(23):4384-90. doi: 10.1039/b813008f. Epub 2008 Oct 22.
A comparative study between bay-region and nonbay-region diol epoxide (DE) derivatives of seventeen carcinogenic polycyclic aromatic hydrocarbons (PAHs) was carried out using the B3LYP/6-31G(d,p) level of density functional theory to understand the factors responsible for the increased carcinogenic activity of bay-region derivatives. Molecular electrostatic potential analysis as well as proton affinity calculations showed that the epoxide sites of bay-region derivatives are much more reactive than the corresponding nonbay-region analogs. The charge delocalization mode in the carbocation intermediates resulting from the protonation reactions was followed through LUMO analysis. The relative aromaticity in the different rings in the arenium ions was gauged by NICS(1)(zz) computations. Both these calculations revealed that the protonated DEs (DEH(+)) are stabilized by higher aromaticity in the bay-region derivatives than the nonbay-region derivatives. Hence, a bay-region DEH(+) can be retained in the reacting medium for a longer time than compared with the DEH(+) formed from a nonbay-region DEs. Thus the high carcinogenic activity of bay-region DEs is attributed to the high reactivity of the epoxide system for protonation and the high thermodynamic stability of the resulting cation. Multiple regression analysis also confirms the above results wherein proton affinity and aromaticity significantly explain the variations in the carcinogenic activity of the molecules under study.
利用密度泛函理论的B3LYP/6-31G(d,p)水平，对17种致癌多环芳烃（PAHs）的湾区二醇环氧化物（DE）衍生物和非湾区二醇环氧化物衍生物进行了比较研究，以了解导致湾区衍生物致癌活性增加的因素。分子静电势分析以及质子亲和力计算表明，湾区衍生物的环氧化物位点比相应的非湾区类似物更具反应性。通过最低未占分子轨道（LUMO）分析追踪了质子化反应产生的碳正离子中间体中的电荷离域模式。通过核独立化学位移（NICS(1)(zz)）计算来衡量芳鎓离子中不同环的相对芳香性。这两种计算都表明，与非湾区衍生物相比，湾区衍生物中质子化的DEs（DEH(+)）通过更高的芳香性而更稳定。因此，与由非湾区DEs形成的DEH(+)相比，湾区DEH(+)可以在反应介质中保留更长时间。因此，湾区DEs的高致癌活性归因于环氧化物体系质子化的高反应性以及所得阳离子的高热力学稳定性。多元回归分析也证实了上述结果，其中质子亲和力和芳香性显著解释了所研究分子致癌活性的变化。
