Quantitative Structure-activity Relationship (qsar). Vi. Modeling the Toxicity of Aliphatic Esters by Means of Molecular Ovality Descriptors

Quantitative structure – activity relationships were developed for the toxicity of 56 aliphatic esters to the protozoan ciliate Tetrahymena pyriformis. The toxicity was measured as A=Log(1/IGC50), where IGC50 is the concentration which inhibits a 50% growth of T. pyriformis. The ovality van der Waals descriptors of molecular shape, ΘiD, i=1,2,3 were used as predictor variables. They were calculated as the ratios of the radii (Θ1D), surfaces (Θ2D), and volumes (Θ3D) of the greatest molecular sphere, corresponding to the vdW surface area of a molecule, and those of the smallest molecular sphere, corresponding to the vdW volume of the same molecule. The goodness of fit was estimated by the coefficient of determination adjusted for the degree of freedom ( 2 adj r > 0.805 for all three ΘiD shape descriptors) and the predictive ability by bootstrapping ( 2 BOOT q > 0.777) and LOO ( 2 LOO q > 0.789) cross-validation statistical procedures. The best model was obtained for the Θ3D predictor variable: r=0.911, 826 . 0 r adj = , 804 . 0 2 = BOOT q 968 . 0 2 = LOO q . An external cross-validation procedure based on odd-even series was also applied with good predictive results ( 2 q > 0.728). The ovality molecular descriptors ΘiD, i=1,2,3 can be easily calculated for any molecule and their physical meaning is clear.