. Author manuscript; available in PMC: 2015 Jun 3.

Published in final edited form as: Chem Res Toxicol. 2009 Sep;22(9):1499–1508. doi: 10.1021/tx900147g

Table 4.

Type-2 Alkene Reactivity: Comparisons of Nucleophilic Indices (ω^-), Thiolate Rate Constants (k_RS-) and Neurotoxic Potencies (IC₅₀'s).

Electrophile	ω^-Cys (−1)	log k₂	log k_RS-	log IC₅₀
NEM	2.51	6.536	7.912	−4.33
Acrolein	2.03	2.596	3.417	−4.28
HNE	1.93	0.938	1.759	−3.40
MVK	1.83	2.048	2.953	−3.48
MA	1.59	−0.936	1.011	−0.34
ACR	1.50	−1.804	0.767	−0.36

Second order rate constants (k₂) were determined for type-2 alkene reactions with L-cysteine at pH 7.4 (n=4-6 experiments). The k₂ values at pH 7.4 were corrected for the corresponding cysteine thiolate concentration (k_RS-) according to the algorithm: log (k_RS- -k₂) = log k₂ + pKa – pH. Inhibition of membrane ³H-dopamine transport was determined in rat striatal synaptosomes exposed in vitro to graded concentrations of each type-2 alkene. The concentration-response data for transport were fitted by nonlinear regression analysis and the respective IC₅₀'s were calculated by the Cheng-Prusoff equation (see 41-43 for methodological details).