The cytotoxicity of ortho alkyl substituted 4-X-phenols: a QSAR based on theoretical bond lengths and electron densities.

摘要

A new method called quantum topological molecular similarity (QTMS) was recently proposed [O'Brien, S. E.; Popelier, P. L. A. J. Chem. Inf. Comp. Sci.2001, 41, 764] and has been shown to be successful in a variety of medicinal, ecological and physical organic QSAR/QSPRs. QTMS method uses electronic descriptors drawn from ab initio wavefunctions of geometry-optimized molecules. We investigated a remarkable and unusual set of ortho alkyl-substituted phenols [Selassie, C. D.; Verma, R. P.; Kapur, S.; Shusterman, A. J.; Hansch, C. J. Chem. Soc., Perkin2002, II, 1112], recently studied by the Hansch group. Our results do not support their proposal that a steric factor is important in the determination of the cytotoxicity of this set of substituted phenols. Thus, we conclude that the cytotoxicity of these sterically encumbered phenols is dependent primarily on electronic and radical effects, and that steric issues do not appear to be a critical distinguishing factor.