SPECTROSCOPIC AND MOLECULAR MODELING STUDIES OF CAFFEINE COMPLEXES WITH DNA INTERCALATORS

Recent studies have demonstrated that caffeine can act as an antimutag en and inhibit the cytoxic and/or cytostatic effects of some DNA inter calating agents. It has been suggested that this inhibitory effect may be due to complexation of the DNA intercalator with caffeine. In this study we employ optical absorption, fluorescence, and molecular model ing techniques to probe specific interactions between caffeine and var ious DNA intercalators. Optical absorption and steady-state fluorescen ce data demonstrate complexation between caffeine and the planar DNA i ntercalator acridine orange. The association constant of this complex is determined to be 258.4 +/- 5.1 M(-1). In contrast, solutions contai ning caffeine and the nonplanar DNA intercalator ethidium bromide show optical shifts and steady-state fluorescence spectra indicative of a weaker complex with an association constant of 84.5 +/- 3.5 M(-1). Tim e-resolved fluorescence data indicate that complex formation between c affeine and acridine orange or ethidium bromide results in singlet-sta te lifetime increases consistent with the observed increase in the ste ady-state fluorescence yield. In addition, dynamic polarization data i ndicate that these complexes form with a 1:1 stoichiometry. Molecular modeling studies are also included to examine structural factors that may influence complexation.