Quantitative structure-activity relationships (QSARs) of Photobacterium phosphoreum toxicity of nitrobenzene derivatives

Abstract The Microtox TM values (acute toxicities to Photobacterium phosphoreum 5 nitrobenzene derivatives are reported, along with the results of ab initio (minimal basis, STO-3G) and semi-empirical (AM1) molecular orbital calculations of electronic properties. QSARs are developed between the acute toxicities and the various calculated parameters. The more rapid semi-empirical calculations are compared to the ab initio results and the advantages and disadvantages of the two methods are considered. As in earlier work, the change in the electronic charge distribution on the nitro group, (QO), in compounds with strongly electron withdrawing substituents, is found to be a significant indicator of high toxicities. The data set is comprised of di-, tri- and tetra substituted compounds. The effect of the increase in the number of substituents and their relative positions on the ring are considered as possible factors affecting acute toxicity. For compounds in which the nitro group is ortho to a substituent with which it may hydrogen-bond, the charge on the nitro group ceases to be a useful indicator of toxicity. The energy of the Highest Occupied Molecular Orbital (HOMO) is found to be highly correlated with QO and alternates with it as the significant parameter in some regressions.