A Case Study of Logistic QSAR Modeling Methods and Robustness Tests

Acute toxicity (15-min EC50) determination of 16 substituted naphthalene compounds to Photobacterium phosphoreum was undertaken according to the standard procedures, while the effects of molecular structures of selected compounds on their toxicity to test microorganisms were logistically conducted using the quantitative structure–activity relationship (QSAR) technique. The relationship was developed as −log EC50=5.5916 (±0.1189)−7.4893(±0.4900)qH++0.7771(±0.0619Elumo+0.0088(±0.0009)α(N=16, R2adj=0.9698, SE=0.0892, P=0.0000). The cluster analyses of individual structure descriptors as well as the quality control chart and Monte Carlo simulation test indicated that the prediction model was reasonable and robust even if tested with several different methods. Furthermore, the quantum chemical parameters entering into the QSAR model were used to discuss the possible toxicity pathways, and the results revealed that the selected compounds were reactive and their toxicity behaviors were complex processes containing physical partition stages as well as biochemical reaction stages.