Interaction of paired homologous series of diacridines and triacridines with deoxyribonucleic acid.

Abstract

Viscometric measurements using covalently closed circular DNA and sonicated rod-like DNA fragments were performed to investigate unwinding and extension of the DNA helix associated with binding of paired homologous series of diacridines and triacridines. The maximum interchromophore distance for members of the diacridine series spans from 15.1 to 27.5 A, permitting the largest of these ligands to cover up to 4 or 5 base-pairs, allowing for helical twist and local unwinding in a bisintercalated complex lacking severe bending or kinking of the DNA backbone. Helix unwinding angles and increments in DNA contour length are characteristic of bifunctional reaction for all the diacridines studied, the DNA lattice appearing to saturate with one ligand molecule bound per 4 base-pairs. The triacridines, whose maximum end-to-end interchromophore distances are the same as those of their paired diacridines, have maximum central-to-terminal interchromophore distances covering the range 7.5-13.8 A and thus have the potential to form trisintercalated complexes with one or two base-pairs sandwiched between each chromophore. However, helix extension and unwinding parameters for the triacridines are similar to those of the diacridines, and we find no evidence of a transition from bifunctional to trifunctional reaction as the homologous series is ascended. In general, the binding site size appears to be 5 base-pairs for the triacridines. The stereochemical requirements for trisintercalation of triacridines are discussed with reference to the present findings and to the work of others.