Substituted 2-hydroxy-1,2-dihydropyrrol-3-ones: fluorescent markers pertaining to oxidative stress and aging.
Previous observations that the aging process correlates with occurrence of certain fluorescent biological pigments have led to numerous efforts in elucidating the chemical nature of the fluorophores generated through reactions of primary amines and various products of lipid peroxidation. In this study, model reactions of saturated aldehydes with aliphatic amines in the presence of peroxides were found to generate structurally unusual fluorescent compounds. Substitution of a lysine-containing peptide for simpler amines has also yielded similar fluorescence. The spectral excitation and emission maxima (around 360 and 430 nm, respectively) of these fluorophores match those widely reported in peroxidized biological objects. The fluorescent compounds in our model studies have been chromatographically isolated and their structures determined through mass spectrometry, NMR spectrometry, and Fourier-transform infrared spectroscopy. The spectrometric data indicate the fluorescent products to be alkylated 2-hydroxy-1,2-dihydropyrrol-3-ones, obtained by the action of 1,2,4-triketone intermediates upon the primary amines. Independent syntheses of several 1,2,4-triketones were carried out. One such triketone reacted with hexylamine to form a fluorescent compound spectroscopically identical to the fluorescent reaction product of hexanal, hydrogen peroxide, and hexylamine.
Chen
P
P
Department of Chemistry, Indiana University, Bloomington 47405, USA.
Wiesler
D
D
Chmelik
J
J
Novotny
M
M
D000447:Aldehydes / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D005453:Fluorescence; D006861:Hydrogen Peroxide; D007700:Kinetics; D015227:Lipid Peroxidation; D008062:Lipofuscin / Q000737:chemistry; D018384:Oxidative Stress; D010455:Peptides / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D013050:Spectrometry, Fluorescence
D000447:Aldehydes; D000588:Amines; D008062:Lipofuscin; D010455:Peptides; D011760:Pyrrolidinones; C010463:n-hexanal; D006861:Hydrogen Peroxide; C007940:hexylamine