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.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Schultz TW,Yarbrough JW,Hunter RS,Aptula AOdoi
10.1021/tx700212usubject
Has Abstractpub_date
2007-09-01 00:00:00pages
1359-63issue
9eissn
0893-228Xissn
1520-5010journal_volume
20pub_type
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