Structural considerations in the interaction of DNA and acridines

The combination in solution of DNA with small amounts of acridine, proflavine, or acridine orange results in markedly enhanced viscosity and a diminution of the sedimentation coefficient of the DNA. These changes are contrary to those expected on the basis of aggregation or simple electrostatic effects. Characteristic changes, which suggest considerable modification of the usual helical structure of DNA, are found in the X-ray diffraction patterns of fibers of the complex with proflavine. It is inferred that these compounds, which are potent mutagens, are intercalated between adjacent nucleotide-pair layers by extension and unwinding of the deoxyribose-phosphate backbone. The hydrodynamic changes are the consequence of the diminished bending between layers, the lengthening of the molecule, and the diminished length-specific mass. The effects are fully reversible at ordinary temperatures. The proposed structural change is compatible with the normal restrictions on bond lengths, angles, and non-bonded contacts, and maintenance of the hydrogen-bonded base pairs perpendicular to the axis of the molecule. Another singly charged dye, pinacyanol, fails to elicit the effects of intercalation, yielding only lowered viscosity and increased sedimentation coefficient.