Reactivity of nitrogen atoms in adenine and (Ade)2Cu complexes towards ribose and 2-furanmethanol: Formation of adenosine and kinetin

• The N6 and N9 of adenine can selectively react with sugars and 2-furanmethanol.
• Adenine copper complexes activate the N9 of adenine and form di-glycated adenine.
• Di-ribosylated adenine and kinetin were formed for the first time from adenine.
• Reaction of adenine with 2-furanmethanol generated kinetin and its isomer.
• Reaction of adenosine with 2-furanmethanol generated kinetin riboside.

To explore the interaction of nucleosides and nucleobases in the context of the Maillard reaction and to identify the selectivity of purine nitrogen atoms towards various electrophiles, model systems composed of adenine or adenosine, glycine, ribose and/or 2-furanmethanol (with and without copper) were studied in aqueous solutions heated at 110 °C for 2 h and subsequently analyzed by ESI/qTOF/MS/MS in addition to isotope labelling techniques. The results indicated that ribose selectively formed mono-ribosylated N6 adenine, but in the presence of (Ade)2Cu complex the reaction mixture generated mono-, di- and tri-substituted sugar complexes and their hydrolysis products of mono-ribosylated N6 and N9 adenine adducts and di-ribosylated N6,9 adenine. Furthermore, the reaction of 2-furanmethanol with adenine in the presence of ribose generated kinetin and its isomer, while its reaction with adenosine generated kinetin riboside, as confirmed by comparing the MS/MS profiles of these adducts to those of commercial standards.