Structural Characterization of a 4-Hydroxy-2-alkenal-Derived Fluorophore That Contributes to Lipoperoxidation-Dependent Protein Cross-Linking in Aging and Degenerative Disease

Modification of proteins by products of lipid peroxidation results in various fluorescent adducts associated with oxidative stress pathophysiology in degenerative disease. Using n-butylamine as a model for the lysine side chain, the structure of the probable major ex/em 360/430-nm fluorophore that arises from cross-linking of two protein-based lysines by one 4-hydroxy-2-alkenal is shown to be a 2-alkyl-2-hydroxy-1,2-dihydropyrrol-3-one iminium. That this fluorophore can be independently generated in higher yield from either 4-oxo-2-alkenals or 3,4-dioxoalkanals supports a proposed mechanistic pathway that involves two 2e oxidations following initial Schiff base formation.