Structure-activity relationships and response-surface analysis of nitroaromatics toxicity to the yeast (Saccharomyces cerevisiae).

Abstract Inhibition of growth of the yeast Saccharomyces cerevisiae ( C miz , the minimum concentration that produced a clear inhibition zone within 12 h) for 24 nitroaromatic compounds was investigated and a quantitative structure–activity relationship (QSAR) developed based on hydrophobicity expressed as the 1-octanol/water partition coefficient in logarithm form, log K ow , electrophilicity based on the energy of the lowest unoccupied orbital ( E lumo ). All nitrobenzene derivatives exhibited enhanced reactive toxicity than baseline. The toxicities of mono-nitrobenzenes and di-nitrobenzenes were elicited by different mechanisms of toxic action. For mono-nitro-derivatives, both significant log K ow based and strong E lumo -dependent relationships were observed indicating that their toxicities were affected both by the penetration process and the interaction with target sites of interaction. The toxicities of di-nitrobenzenes were greater than mono-nitrobenzenes and no log K ow -dependent but highly significant E lumo -based relationship was obtained. This suggests that toxicity of di-nitrobenzenes was highly electrophilic and involved mainly their in vivo electrophilic interaction with biomacromolecules. In an effort to model the elevated toxicity of all nitrobenzenes, a response–surface analysis was performed and this resulted in a highly predictive two-variable QSAR without reference to their exact mechanisms ( C miz =0.41 log K ow −0.89 E lumo −0.46, r 2 =0.87, Q 2 =0.86, n =24).