Two biologically-active thiols, N-acetylpenicillamine (NAP) and 2-mercaptobenzothiazole (MBT), were studied in this thesis. NAP is known to combine with nitric oxide (NO) to produce S-nitroso-N-acetylpenicillamine (SNAP) and MBT is a known allergen.

The formation, reaction dynamics, and detailed kinetics and mechanism of the reaction between nitrous acid (HNO₂), prepared in situ, and NAP to produce SNAP were studied. The reaction is first order in nitrite, NAP and acid in pH conditions at or slightly higher than the pK_a of HNO₂. Both HPLC and quadrupole time-of-flight mass spectrometry techniques confirmed the formation of SNAP and the absence of any other products. Cu(I) ions were found to be effective SNAP-decomposition catalysts. The formation of SNAP occurs through two distinct pathways. One involves the direct reaction of NAP and HNO₂ to form SNAP and eliminate water, and the second pathway involved the initial formation of the nitrosyl cation, NO⁺, which then nitrosates the thiol. The bimolecular rate constant for the reaction of NAP and HNO₂ was derived as 2.69 M^-1 s^-1, while that of direct nitrosation by the nitrosyl cation was 3.00 x 10⁴ M^-1 s ^-1. A simple reaction network made up of four reactions was found to be sufficient in simulating the formation kinetics and acid-induced decomposition of SNAP.

The chemical mechanism leading to MBT's allergenicity is unknown. It was hypothesized that the thiol group is critical to MBT's covalent binding/haptenation to nucleophilic protein residues. Hypochlorous acid oxidized MBT to the disulfide, 2, 2'-dithiobis(benzothiazole) (MBTS), within the glove matrix. Cysteine reduced MBTS to MBT with subsequent formation of the mixed disulfide 2-amino-3-(benzothiazol-2-yl disulfanyl)-propionic acid. Simultaneous reduction of MBTS and disulfide formation with Cys34 on bovine serum albumin was observed, suggesting a potential route of protein haptenation through covalent bonding between cysteinyl residues on proteins and the MBT/MBTS thiol moiety. Guinea pigs were sensitized to MBT using a modified guinea pig maximization assay (GPMT) and cross-reactivity towards MBTS and the free thiol-lacking or blocked compounds benzothiazole (BT), 2-hydroxybenzothiazole (HBT) and 2-(methylthio)benzothiazole (MTBT) assessed. MBT and MBTS, but not BT, HBT or MTBT elicited allergic contact dermatitis (ACD) in MBT-sensitized animals.