1H NMR study of the complexation of aromatic drugs with dimethylxanthine derivatives

► The self- and hetero-association of dimethylxanthines with aromatic drugs was studied. ► The energetics of association is independent on the structure of the dimethylxanthines. ► The dimethylxanthines possess higher interceptor ability as compared to Caffeine. With an aim of searching efficient interceptors of aromatic drugs, the self- and hetero-association of dimethylxanthine derivatives with different structures, selected according to Strategy 1 (variation of the position of methyl groups) and Strategy 2 (variation of the length of (CH2)nCOOH group), with aromatic drug molecules: Ethidium Bromide, Proflavine and Daunomycin, were studied using 1H NMR spectroscopy. It was found that the association proceeds in a form of stacking-type complexation and its energetics is relatively independent on the structure of the dimethylxanthines. However, on average, the dimethylxanthines possess higher hetero-association constant and, hence, higher interceptor ability as compared to the trimethylxanthine, Caffeine, used during the past two decades as a typical interceptor molecule.