Determination of a Structure-Activity Relationship for Analogs of the Toxin 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Using Ab Initio Molecular Orbital Calculations

Abstract

A series of compounds analogous to the toxin 2~3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) were studied in order to determine a structure-activity relationship for predicting the activity of such compounds based om various electronic and steric structural parameters. TCDD was found to act as an electron acceptor in the formation of a Mulliken charge transfer complex. A high correlation was found between the activity of a molecule and the energy of the electron accepting molecular orbital with~an additional steric parameter designating substitution at sites 1, 4, 6, or 9 of the molecule. The energies of the acceptor orbital of the TCDD analogs were arrived at using SCF-MO calculations with the molecular fragment (FSGO) basis set. This regression line can be used to determine the relative toxicity of very potent toxins within the accuracy of present protein binding radioassay techniques without ever handling the chemical.