Relationships Between Descriptors for Hydrophobicity and Soft Electrophilicity in Predicting Toxicity

Abstract

The toxicity of chemicals is orthogonal with individual molecular descriptors used to quantify hydrophobicity and soft electrophilicity when considering large data sets. Estimating the toxicity of reactive chemicals requires descriptors of both passive transport and the stereoelectronic interaction, which are largely independent processes. QSARs using either log P or an electronic parameter alone are only significant for sets of chemicals that represent special, albeit some important, cases in QSAR.

Chemicals were clustered according to their reactivity as soft electrophiles by defining isoelectrophilic windows along the toxicity response surface. Within these narrow windows of reactivity, the variation of toxicity was explained by the variation of log P. We observed that the dependence of toxicity on log P in different isoelectrophilic windows decreased as reactivity increased. The data are consistent with toxicity models where competing nucleophilic interaction sites are distributed along the transport route of the chemicals.

Key Words:

• aquatic toxicity
• descriptors
• log P
• reactivity
• electrophiles