Spectroscopic and molecular modeling studies of caffeine complexes with DNA intercalators.
Recent studies have demonstrated that caffeine can act as an antimutagen and inhibit the cytoxic and/or cytostatic effects of some DNA intercalating 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 modeling techniques to probe specific interactions between caffeine and various DNA intercalators. Optical absorption and steady-state fluorescence data demonstrate complexation between caffeine and the planar DNA intercalator acridine orange. The association constant of this complex is determined to be 258.4 +/- 5.1 M-1. In contrast, solutions containing 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. Time-resolved fluorescence data indicate that complex formation between caffeine and acridine orange or ethidium bromide results in singlet-state lifetime increases consistent with the observed increase in the steady-state fluorescence yield. In addition, dynamic polarization data indicate that these complexes form with a 1:1 stoichiometry. Molecular modeling studies are also included to examine structural factors that may influence complexation.
Larsen
R W
RW
Department of Chemistry, University of Hawaii at Manoa, Honolulu 96822, USA. rlarsen@gold.chem.hawaii.edu
Jasuja
R
R
Hetzler
R K
RK
Muraoka
P T
PT
Andrada
V G
VG
Jameson
D M
DM
D000165:Acridine Orange / Q000737:chemistry / Q000494:pharmacology; D055592:Biophysical Phenomena; D001703:Biophysics; D002110:Caffeine / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D004996:Ethidium / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000737:chemistry; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D009153:Mutagens / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013816:Thermodynamics
D005456:Fluorescent Dyes; D007364:Intercalating Agents; D009153:Mutagens; D002110:Caffeine; D004247:DNA; D004996:Ethidium; D000165:Acridine Orange