Structure–Toxicity Relationships for Three Mechanisms of Action of Toxicity toVibrio fischeri

Quantitative structure–activity relationships (QSARs) have been developed with the logarithm of the inverse of 15-min toxicity (pT15) toVibrio fischeri(the acute Microtox test). Statistically, robust QSARs were found for alkanones acting by the nonreactive, baseline narcosis mechanism of action [pT15=0.99(logKow)−2.08,n=6,s=0.24,r2=0.988,F=405]; aldehydes acting by the Schiff base-forming mechanism of electrophilicity [pT15=0.55(logKow)−0.58,n=6,s=0.07,r2= 0.994,F=782]; and alkenals acting by the Michael-type acceptor mechanism of electrophilicity [pT15=0.52(logKow)+0.35,n=6,s=0.19,r2=0.914,F=54.5]. Efforts to model toxicity across mechanism of action resulted in the development of a response surface [pT15=0.79(logKow)−1.17(ELUMO)−0.41,n=19,s=0.46,r2=0.892,F=75.3]. In addition, an excellent correlation was found betweenTetrahymena pyriformis[log(1/IGC50)] andV. fischeri. [log(1/IGC50)=0.86(pT15)−0.25,n=19,s=0.25,r2=0.957,F=405] toxicity.