Chemical characterization of isocyanate-protein conjugates

Abstract

The rates of reaction of toluene diisocyanate (TDI) and hexamethylene diisocyanate (HDI) with the protein, human serum albumin, were studied. The reaction of TDI with protein was assessed by determining the total number of TDI residues bound as well as those bound in a monoureido linkage. There was a 3.5-fold greater number of residues bound in the bisureido linkage as compared to the monoureido linkage. The reaction of HDI with human serum albumin was quantified by combined assays of gas chromatography of the hexamethylenediamine formed after acid hydrolysis of the conjugate and by amino acid analyses of the protein. HDI isocyanate groups reacting with the lysyl residues and other sites on the protein molecule formed at least two reaction products, one which was easily hydrolyzable by acid and the other resistant to hydrolysis. The chemical structures proposed by these observations are similar to those of classical hapten derivatives and suggest that such derivatives may be immunogenic and/or allergenic in some workers exposed to the vapors of these reagents.