QSAR model of the phototoxicity of polycyclic aromatic hydrocarbons

A Quantitative Structure-Activity Relationship (QSAR) study of 67 polycyclic aromatic hydrocarbons (PAHs) is performed and a prediction rule for the phototoxicity of these compounds is proposed. The geometry of all PAHs was optimized by semi-empirical method and used to calculate the following electronic descriptors: the highest occupied molecular orbital energy (EHOMO), the lowest unoccupied molecular orbital energy (ELUMO) and the GAP (EHOMO−ELUMO) between them. The relationships between these molecular descriptors and the photo-induced toxicity are non-linear, and Gaussian type functions were used to linearize them. The data set was autoscaled and partial least squares (PLS) with leave-one-out cross-validation was used for building the regression model. After the model was validated, the phototoxicity was predicted for a set of molecules in which experimental measurements are unknown. Pentaphene, benzo[b]chrysene and dibenz[a.j]anthracene are among the compounds potentially phototoxic as predicted by the model. A new GAP range (7.2±0.7 eV) is proposed for the classification of phototoxic compounds, and a larger cutoff suggested for the normalized lethal time as log(1/ALT)≤−2.95.