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.