| Abstract
| - Diisocyanates (dNCOs) are the most commonly reported cause of chemically induced occupationalasthma, but the ultimate antigenic form is unknown. Reactions of the three most common monomericdNCOs, hexamethylene dNCO (HDI), methylene diphenylisocyanate (MDI), and toluene dNCO (TDI),with cysteine methyl ester (CME) gave the corresponding bis-dithiocarbamates (HDI−CME, TDI−CME,and MDI−CME). The dissociation kinetics of these bis-thiocarbamates, in aqueous conditions, wasfollowed spectrophotometrically under varying pH and temperature conditions. Reaction of the adductswith methylamine or human serum albumin (HSA) produced diurea, monourea, and diamine products,and this was consistent with the base-catalyzed elimination reaction (E1cB) pathway being the dominant,but not exclusive, dissociation mechanism. The hydrolysis of the adducts was first-order with respect toOH- concentration and overall second-order (HDI−CME, k = 3.36 × 102 M-1 min-1; TDI−CME, k =2.49 × 104 M-1 min-1; and MDI−CME, k = 5.78 × 104 M-1 min-1 at pH 7.4) with deviation fromsecond-order when the dNCO had an aromatic functional group. Arrhenius plots gave activation energies(HDI−CME, Ea = 70.6 kJ/mol; TDI−CME, Ea = 46.1 kJ/mol; and MDI−CME, Ea = 44.5 kJ/mol) thatwere consistent with the following order of stability: HDI−CME > TDI−CME > MDI−CME. Therefore,the stability of different dNCO-derived thiocarbamates in aqueous environments can vary greatly.Thiocarbamate dissociation rates and type of products formed may potentially influence antigenicity andsubsequent hypersensitivity/toxic reactions following dNCO exposures.
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