Molecular interaction between riboflavin and salicylic acid derivatives in nonpolar solvents

The interaction of riboflavin-2',3',4',5'-tetrabutyrate (I) with salicylic acid (II), aspirin (acetylsalicylic acid, III), and salicylamide (IV) has been spectroscopically investigated to determine the binding mechanism. NMR and absorption spectra were measured in nonpolar solvents. The association constant K of the formation of complex was calculated from the absorption spectra. Compounds I and II form a 1:1 cyclic hydrogen-bonded dimer through the N-3 proton and the C-2 carbonyl oxygen of the isoalloxazine ring, and the carboxylic hydroxyl proton and carbonyl oxygen of II. Compounds I and III form a 1:1 cyclic hydrogen-bonded dimer by the same mode. Compound IV forms a 1:1 cyclic hydrogen-bonded dimer with I through the N-3 proton and the C-2 carbonyl oxygen of the isoalloxazine ring, and the amino proton and the carbonyl oxygen of IV. Salicylates produce marked changes in the absorption spectra of I. These spectral changes are attributed to the formation of the hydrogen-bonded dimer. It appeared that the strongest complex was formed with salicylic acid, a weaker one with aspirin, and an even weaker one with salicylamide.