Heterodimeric molecules including nucleic acid bases and 9-aminoacridine. Spectroscopic studies, conformations, and...

Heterodimeric molecules have been examined in which the 9-amino-6-chloro-2-methoxyacridine ring is linked to the nucleic acid bases adenine, thymine, and guanine by polymethylenic chains (CH2)n of varying length (n = 3, 5, 6). A detailed analysis has been performed, including hypochromism measurement in the UV, chemical shift variations in Fourier transform proton magnetic resonance, and fluorescence emission. All these techniques show that all molecules exist mainly under folded conformations in water in the temperature range 0-90 degrees C, with the acridine and the base rings being stacked one on top of the other. The thermodynamic parameters for the folded in equilibrium unfolded conformational equilibrium were estimated. The geometry of the intramolecular complexes could be determined. (1) All these data give information on the strength and nature of the base-acridine interactions as a function of different parameters such as solvent, temperature, etc. (2) The molecules under study constitute "spectroscopic models" for the drug-base complexes as they occur in DNA. In particular, we show the dramatic influence of the relative orientations of the two stacked chromophores in the complex upon the magnitude of % H, the percent hypochromism. The quenching and enhancement of acridine fluorescence emission induced respectively by guanine and adenine is evidenced and quantitatively estimated. (3) These base-acridine heterodimers bind to DNA to an extent that is inversely proportional to their degree of intramolecular stacking.