Mechanistic Aspects of Alloxan Diabetogenic Activity:  A Key Role of Keto−Enol Inversion of Dialuric Acid on Ionization

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2006-06, Vol.110 (22), p.7272-7278
• Main Authors: Czerwiñska, Małgorzata, Sikora, Adam, Szajerski, Piotr, Adamus, Jan, Marcinek, Andrzej, Gȩbicki, Jerzy, Bednarek, Paweł
• Format: Article
• Language: English
• Subjects: Alloxan - chemistry; Alloxan - metabolism; Animals; Barbiturates - chemistry; Barbiturates - metabolism; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - metabolism; Ions; Molecular Structure; Spectrum Analysis; Stereoisomerism
• ISSN: 1089-5639; 1520-5215
• DOI: 10.1021/jp0614594

The inversion of the keto−enol stability order of dialuric acid on ionization was calculated and verified experimentally. The radical cations in both forms were characterized. The spectrum of the keto form was observed upon direct ionization of dialuric acid under matrix conditions, whereas the enol form was formed upon a sequential electron−proton−proton attachment to alloxan under acidic aqueous condition. Facilitation of the one-electron oxidation of dialuric acid upon its enolization can result in a more effective formation of superoxide radical anion in the process of its auto-oxidation. This process is discussed in reference to the alloxan diabetogenic action. Both neutral keto and enol forms are energetically close, and under favorable conditions, the auto-oxidation of dialuric acid could involve participation of the enol form.