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

• Published in: Bioorganic & medicinal chemistry letters 2006-03, Vol.16 (5), p.1249-1254
• Main Authors: Loader, R.J., Singh, N., O’Malley, P.J., Popelier, P.L.A.
• Format: Article
• Language: English
• Subjects: Ab initio; Alkylation; Atoms in molecules; Biological and medical sciences; Cell Death - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical Phenomena; Chemistry, Physical; Electron density; Electrons; Medical sciences; Models, Chemical; Molecular Structure; Partial least square; Phenols; Phenols - chemistry; Phenols - toxicity; QSAR; QTMS; Quantitative Structure-Activity Relationship; Quantum chemical topology; Toxicology; Various organic compounds; Verma
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.11.079

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., Perkin 2002, 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.