title: Kinetics and mechanism of the addition of nucleophiles to alpha,beta-unsaturated thiol esters.
abstract: Compounds containing the UV-absorbing chromophores p-methoxycinnamate, p-methoxycinnamide, or anthranilate and an alpha,beta- or alpha,beta,gamma,delta-unsaturated thiol ester (crotonyl or sorboyl) have been prepared. These compounds are subject to nucleophilic attack at the C=C conjugated to the thiol ester carbonyl group. The kinetics of the reactions of these thiol esters with N-acetyl-l-cysteine (NAC), N-acetylcysteamine, and N(2)-acetyl-L-lysine (NAL) have been studied, and the thiol addition products have been identified. The reaction rates increased at higher pH, and the reaction of NAC thiolate with a crotonyl thiol ester in 1:1 (v/v) acetonitrile/aqueous HEPES exhibited buffer catalysis as a result of protonation of the enolate intermediate. At the same concentration, NAC underwent approximately 300-fold more reaction than NAL with a crotonyl thiol ester at pH 9.8. Additionally, a crotonyl thiol ester was found to be 7.9 times more reactive than a sorboyl thiol ester toward NAC addition. These unsaturated thiol esters may serve as a means of covalently binding UVA and UVB sunscreens to the outer layer of skin to provide long-lasting protection.
authors.affiliation: Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA.
authors.forename: Rosemarie F
authors.initials: RF
authors.lastname: Hartman
authors.forename: Seth D
authors.initials: SD
authors.lastname: Rose
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D004952:Esters / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D004952:Esters; D013438:Sulfhydryl Compounds; D000111:Acetylcysteine