QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS (QSARS) OF PHOTOBACTERIUM-PHOSPHOREUM TOXICITY OF NITROBENZENE DERIVATIVES

The Microtox(TM) values (acute toxicities to Photobacterium phosphoreu m) of 85 nitrobenzene derivatives are reported, along with the results of ab initio (minimal basis, STO-3G) and semi-empirical (AM1) molecul ar orbital calculations of electronic properties. QSARs are developed between the acute toxicities and the various calculated parameters. Th e more rapid semi-empirical calculations are compared to the ab initio results and the advantages and disadvantages of the two methods are c onsidered. As in earlier work, the change in the electronic charge dis tribution on the nitro group, (QO), in compounds with strongly electro n withdrawing substituents, is found to be a significant indicator of high toxicities. The data set is comprised of di-, tri- and tetra subs tituted compounds. The effect of the increase in the number of substit uents and their relative positions on the ring are considered as possi ble 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 signific ant parameter in some regressions.