Structure-reactivity relationships and substituent effects on carbocation stability in benzo[a]anthracene (BA) derivatives have been studied computationally at the B3LYP/6-31G and MP2/6-31G levels. Bay-region carbocations are formed by O-protonation of the 1,2-epoxides in barrierless processes. This process is energetically more favored as compared to carbocation generation via zwitterion formation/O-protonation, via single electron oxidation to generate a radical cation, or via benzylic hydroxylation. Relative carbocation stabilities were determined in the gas phase and in water as solvent (PCM method). Charge delocalization mode in the BA carbocation framework was deduced from NPA-derived changes in charges, and substitution by methyl or fluorine was studied at different positions selected on basis of the carbocation charge density. A bay-region methyl group produces structural distortion with consequent deviation from planarity of the aromatic system, which destabilizes the epoxide, favoring ring opening. Whereas fluorine substitution at sites bearing significant positive charge leads to carbocation stabilization by fluorine p-pi back-bonding, a fluorine atom at a ring position which presented negative charge density leads to inductive destabilization. Methylated derivatives are less sensitive to substituent effects as compared to the fluorinated analogues. Although the solvent decreases the exothermicity of the epoxide ring-opening reactions due to greater stabilization of the reactants, it provokes no changes in relative reactivities. Relative energies in the resulting bay-region carbocations are examined taking into account the available biological activity data on these compounds. In selected cases, quenching of bay-region carbocations was investigated by analyzing relative energies (in the gas phase and in water) and geometries of their guanine adducts formed via covalent bond formation with the exocyclic amino group and with the N-7.

中文翻译：

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来自苯并[a]蒽的氧化代谢产物的碳正离子：它们的甲基化和氟化衍生物和鸟嘌呤加合物的计算研究。

已在B3LYP / 6-31G和MP2 / 6-31G含量上对苯并[a]蒽（BA）衍生物的结构反应关系和取代基对碳正离子稳定性的影响进行了研究。湾区碳阳离子是通过无障碍过程中1,2-环氧化物的O质子化形成的。与通过两性离子形成/ O-质子化，通过单电子氧化以生成自由基阳离子或通过苄基羟基化生成碳阳离子相比，该方法在能量上更受青睐。测定了在气相中和在水中作为溶剂的相对碳正离子稳定性（PCM方法）。由NPA衍生的电荷变化推导了BA碳正离子骨架中的电荷离域模式，并在根据碳正离子电荷密度选择的不同位置研究了甲基或氟取代。海湾区域的甲基会产生结构扭曲，从而偏离芳族体系的平面度，从而使环氧化物不稳定，有利于开环。尽管在带有明显正电荷的位点处的氟取代会通过氟p-pi背键导致碳阳离子稳定，但在环位置呈现负电荷密度的氟原子则会导致感应不稳定。与氟化类似物相比，甲基化衍生物对取代基的影响不那么敏感。尽管由于反应物的更大的稳定性，溶剂降低了环氧化物开环反应的放热性，但它不会引起相对反应性的改变。考虑到有关这些化合物的可用生物活性数据，检查了所得海湾区域碳正离子中的相对能量。在某些情况下，通过分析相对能量（在气相和水中）以及通过与环外氨基和N-7共价键形成的鸟嘌呤加合物的几何形状，研究了湾区碳阳离子的猝灭。