Drug Self-Assembly on DNA: Sequence Effects with trans-bis-(4-N-methylpyridiniumyl)diphenyl Porphyrin and Hoechst 33258.

Abstract Self assembly in biological systems is increasingly being recognised as an important phenomenon. We have examined two model systems: the cationic meso-substituted free base porphyrin derivative frans-bis-(4-N-methylpyridiniumyl)diphenyl porphyrin (t-H2P) and Hoechst 33258 (Hoechst) both of which were known to assemble on DNA. t-H2P self-assembles in solution under appropriate conditions, whereas Hoechst does not. By varying ionic strength and ligand: DNA mixing ratios, these features together with their different steric constraints have led to quite different DNA binding behaviour. Hoechst on poly[d(A-T)]2 stacks across the major groove, probably after filling its well established monomeric minor groove binding mode. By way of contrast the Hoechst/poly[d(G-C)]2 self-assembled aggregates involve partially intercalated molecules stacking in the major groove. The binding mode adopted by t-H2P with poly[d(A-T)]2 and poly[d(G-C)]2 appears to be kinetically controlled and to be determined by the pre-ex...