The interaction of multiply charged intercalating heterocycles with DNA

The interaction with DNA of two aromatic nitrogen heterocycles, 1 and 2, which at pH 6 have two positive charges on their ring systems and two cationic side chains, have been determined. A third similar compound, 3, with a single side chain and reduced ring charge, was analyzed as a control. Viscometric titrations with sonicated DNA indicated that all three compounds bind to DNA by intercalation. Spectrophotometric binding studies as a function of ionic strength indicated that both 1 and 2 bind to DNA as tetracations at pH 6. These are the first examples of intercalators with two charges directly on the intercalating ring system. Dissociation kinetics experiments as a function of ionic strength confirmed that 1 and 2 bind to DNA as tetracations. Compound 1 has a G · C base‐pair binding preference, 2 seems to prefer binding to alternating pyrimidine–purine sequences regardless of the composition, and 3 has no significant binding specificity.