title: Aquatic toxicity and abiotic thiol reactivity of aliphatic isothiocyanates: Effects of alkyl-size and -shape.
abstract: Aquatic toxicity data in the TETRATOX assay and reactivity data in an abiotic thiol assay were collected for a series of aliphatic isothiocyanates. These compounds can act as Michael-type acceptors with N-hydro-C-mercapto-addition to cellular thiols as a molecular mechanism of action. Comparison of both toxicity and reactivity among the analogues revealed that derivatives with a branch hydrocarbon moiety, especially branched in the β-position were less toxic and less reactive. In contrast, the di-isothiocyanate and the allyl and propargyl derivatives are more toxic than their 1-alkyl homologues. The toxicity and reactivity differences are consistent but except for the tert-butyl-derivative not remarkable. The differences are due to variations in steric hindrance at the reaction center. For the mono-isothiocyanates compounds toxicity (IGC(50)) is linearly related to thiol reactivity (EC(50)): log(1/IGC(50))=1.33(log(1/EC(50)))-0.41; n=23, s=0.24, r(2)=0.911, q(2)=0.907, F=215.
authors.affiliation: The University of Tennessee, College of Veterinary Medicine, Department of Comparative Medicine, 2407 River Drive, Knoxville, TN 37996-4543, USA.
authors.forename: T Wayne
authors.initials: TW
authors.lastname: Schultz
authors.forename: Jason W
authors.initials: JW
authors.lastname: Yarbrough
authors.forename: Tyler B
authors.initials: TB
authors.lastname: Pilkington