Synthesis and characterization of novel tris-intercalators having potentially two different DNA binding modes

Novel DNA binding ligands (3 and its stereoisomer 4) which contain three potentially intercalating units in a linear molecular skeleton were prepared. The melting point of calf thymus DNA (Tm ) was determined in the presence of 3 or 4 to show that these compounds possess a high binding affinity for DNA and that 3 stabilizes the double helix more than does isomeric 4. Upon mixing with DNA, circular dichroism spectra were induced for both the acridine and the anthraquinone chromophores of 3 and 4. A DNase I footprinting study indicated that these compounds intercalate in AT-rich DNA sequences. Viscometric analysis using sonicated calf thymus DNA and closed, circular, supercoiled plasmid DNA given an unwinding angle of 49° and 47° for 3 and 4, respectively. These results indicate that both compounds serve as trifunctional intercalators.