A QSAR APPROACH FOR ESTIMATING THE AQUATIC TOXICITY OF SOFT ELECTROPHILES [QSAR FOR SOFT ELECTROPHILES]

This work demonstrated that descriptors of soft electrophilicity for a romatic chemicals such as average superdelocalizability and LUMO energ y could be used together with the hydrophobicity descriptor, log P, to explain the variation of acute toxicity of substituted benzenes, phen ols, and anilines to fish. The hydrophobicity and soft electrophilicit y descriptors were shown to be orthogonal for the 114 chemicals studie d. For proelectrophiles, the structure-toxicity relationships accurate ly predict toxicity when the stereoelectronic parameters were computed for the metabolic activation products. The QSAR for acute toxicity us ing these molecular descriptors defines a toxicity plane which include s several modes of toxic action. Type (I) narcotics are chemicals loca ted in the region of low reactivity where toxicity varies with hydroph obicity alone. Type (II) narcotics are more toxic than type (I) narcot ics at similar values of log P, and the increase can be explained by s tronger electronic interactions with cellular soft nucleophiles. Highl y reactive soft electrophiles which have dissociating protons such as 2,4,-dinitrophenol produce symptoms of respiratory uncouplers. Those w ithout dissociating protons produce symptoms of reactive toxicity cons istent with covalent binding.