Glutathione reactivity with aliphatic polyisocyanates.

Area of Science:

• Toxicology
• Biochemistry
• Analytical Chemistry

Background:

• Isocyanates are industrial chemicals with known inhalation risks.
• Glutathione (GSH) is a key antioxidant in the airways, involved in metabolizing foreign compounds.
• The reactivity of modern polyisocyanates with GSH is not well understood.

Purpose of the Study:

• To investigate the reaction between aliphatic polyisocyanates and glutathione under physiological conditions.
• To identify and characterize the resulting adducts using advanced analytical techniques.

Main Methods:

• Liquid chromatography (LC) coupled with mass spectrometry (MS) and tandem MS/MS.
• Electrospray ionization in positive ion mode.
• Collision-induced dissociation (CID) for structural analysis.

Main Results:

• Identified tris(GSH)-isocyanate adducts as major products from common hexamethylene diisocyanate (HDI) formulations (isocyanurate, biuret).
• Characterized bis(GSH)-isocyanate adducts from the uretdione form of HDI.
• MS/MS fragmentation patterns supported S-linkage of GSH to isocyanate groups.

Conclusions:

• Industrially relevant aliphatic polyisocyanates readily conjugate with GSH.
• The primary products are S-linked tris(GSH)-conjugates.
• This reaction pathway may be significant in the body's response to respiratory isocyanate exposure.