A QSAR Approach for Estimating the Aquatic Toxicity of Soft Electrophiles [QSAR for Soft Electrophiles

Abstract

AbstractThis work demonstrated that descriptors of soft electrophilicity for aromatic chemicals such as average superdelocalizability and LUMO energy could be used together with the hydrophobicity descriptor, log P, to explain the variation of acute toxicity of substituted benzenes, phenols, and anilines to fish. The hydrophobicity and soft electrophilicity descriptors were shown to be orthogonal for the 114 chemicals studied. For proelectrophiles, the structure‐toxicity relationships accurately predict toxicity when the stereoelectronic parameters were computed for the metabolic activation products. The QSAR for acute toxicity using these molecular descriptors defines a toxicity plane which includes several modes of toxic action.Type (I) narcotics are chemicals located in the region of low reactivity where toxicity varies with hydrophobicity alone. Type (II) narcotics are more toxic than type (I) narcotics at similar values of log P, and the increase can be explained by stronger electronic interactions with cellular soft nucleophiles. Highly reactive soft electrophiles which have dissociating protons such as 2,4,‐dinitrophenol produce symptoms of respiratory uncouplers. Those without dissociating protons produce symptoms of reactive toxicity consistent with covalent binding.