The Electronic Factor in QSAR: MO-Parameters, Competing Interactions, Reactivity and Toxicity

Abstract

Reactive chemicals pose unique problems in the development of SAR and QSAR in environmental chemistry and toxicology. Models of the stereoelectronic interactions of reactive toxicants with biological systems require formulation of parameters that quantify the electronic structure of the chemicals. A review of early approaches to modeling reactivity is presented in this work, with emphasis on the generalized poly-electronic perturbation theory. Applications of GPPT are demonstrated with QSARs for predicting toxicity of soft electrophiles and proelectrophiles using superdelocalizability and the charges on frontier orbitals. Prediction of toxicity for hard electrophiles such as organophosphates require atomic charges and bond orders in the QSAR. Special considerations for the orthogonality of factors and for the classification of reactive chemicals are reviewed.

Key Words:

• molecular descriptors
• electrophiles
• quantum chemistry
• reactivity
• toxicity