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Chiral Pesticides in Chiral Biological Enciroments: Do We Need to Move Beyond our Achiral Perspective.
Citation:
Kenneke, J. Chiral Pesticides in Chiral Biological Enciroments: Do We Need to Move Beyond our Achiral Perspective. Presented at Southeastern Regional Meeting of the American Chemical Society, Raleigh, NC, November 14 - 17, 2012.
Impact/Purpose:
Presentation to be presented Southeastern Regional Meeting of the American Chemical Society, November 14-17, 2012, Raleigh, NC
Description:
When a chemical stressor crosses the body barrier it becomes an internal dose. In the context of risk assessment, this internal dose provides a critical linkage between exposure and effects. Pharmacokinetic processes (i.e., what the body does to the chemical) such as absorption, distribution, metabolism, and elimination (ADME) can have a profound impact on internal dose. Since many ADME processes are enzyme-based, the stereoisomers of chiral molecules can interact differently with the chrial environment of these enzymes and yield different ADME properties, internal doses, and effects. We have conducted extensive in vitro ADME studies on various chiral pesticides and found significant kinetic, mechanistic, and interspecies differences between stereoisomers. These include differences in metabolic stability, bioaccumulation, metabolite formation, enzyme inhibition, and toxicity. We are now utilizing these results in conjunction with enzyme docking and other computational approaches to develop stereospecific ADME models to improve the risk assessment of chiral chemicals.
