Quantum chemical and theoretical predictions of toxicity
Joyce J. Kaufman · Journal of Environmental Science and Health Part A Environmental Science and Engineering · 1982
Theoretical and quantum chemical predictions of toxicity and toxicology are even more challenging than prediction of pharmacology, which is usually a one‐stage event at a target site. For toxicity and toxicology, we have developed the concept of the “toxic triggering event,”; which then leads to the cascade of subsequent physiological events. The strategy for computer‐generated predictions in this area includes as the major components chemical automated substructure and “toxicophore”; identification by powerful chemical structure and substructure searching techniques, quantum chemical calculations (desirably ab‐initio, incorporating optimal strategies for such computations on large molecules) on both the toxicant and its metabolites (the structures of which were generated by computer‐assisted tracing of metabolic pathways), generation of the three‐dimensional electrostatic molecular potential contour maps around the toxicants and tneir metabolites and matching of these maps by reverse image holography for new compounds whose toxicity has not yet been tested experimentally against those with a known toxic mechanism, matching of intermolecular interaction maps of untested compounds with known toxicants combined with matching observed physiologic signs and symptoms with “toxic triggering events,”; and specific pathologies for both tracking and backtracking, and using the concepts of both the dynamic balance of endogenous biomolecules and interactions with these biomolecules.