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Verification of the structural alerts for Michael acceptors
Chemical research in toxicology (2007)
  • Terry W Schultz, University of Tennessee - Knoxville
  • J W Yarbrough
  • R S Hunter
  • A O Aptula
Abstract

A diverse series of polarized alpha,beta-unsaturated and related compounds were evaluated for reactivity with a spectrophotometric assay using the sulfhydryl group in the form of the cysteine residue of the tripeptide GSH as a model nucleophile. The reactive end point (RC 50) calculations were compared to previously described structural alerts based on conventional organic chemistry. This comparison focused on polarized alpha,beta-unsaturates, including ones containing an aldehyde, ketone, ester, sulfoxide, sulfone, sulfonate, nitro, or cyano moiety as well as ortho- and para-pyridino compounds and ortho- and para-quinones. The alerts were coded by substructure and are available in open-source software ( http://sourceforge.net/projects/chemeval). Comparisons of reactivity between selected analogues revealed that only the polarized alpha,beta-unsaturates were reactive. These results verified the coded structural alerts that define the applicability domain for Michael acceptor electrophiles.

Publication Date
2007
Citation Information
Terry W Schultz, J W Yarbrough, R S Hunter and A O Aptula. "Verification of the structural alerts for Michael acceptors" Chemical research in toxicology Vol. 20 Iss. 9 (2007)
Available at: http://works.bepress.com/terry_schultz/14/