SUPRAMOLECULAR CHEMISTRY .71. INTERCALATION MECHANISMS WITH DS-DNA - BINDING MODES AND ENERGY CONTRIBUTIONS WITH BENZENE, NAPHTHALENE, QUINOLINE AND INDOLE-DERIVATIVES INCLUDING SOME ANTIMALARIALS

Intercalation mechanisms into double-stranded calf thymus DNA have bee n probed with 38 different ligands, largely based on naphthalene or qu inoline systems, It is shown how NMR shift and line width changes of t he ligand signals can be used to unequivocally differentiate intercala tion from groove binding modes, and to obtain by curve fitting associa tion constants K. These show acceptable agreement if derived from seve ral independent NMR signals. Less reliable information is obtained fro m selected UV titrations, from DNA melting differences, from calorimet ric measurements and from affinity comparison to polyamines, the latte r being based on a fluorescence assay with ethidium bromide. In contra st to literature expectations the naphthalene-shaped ligands show simi lar affinities irrespective of the presence of nitrogen atoms, or even of charges within the aromatic system, Quinolinium and naphthalene de rivatives only intercalate if they bear a positively charged side chai n, and then with similar binding constants. Comparison of all systems as well as salt effects demonstrate that the binding can be quantified with additive contributions from salt bridges of the ammonium centres in the side chains, and from the stacking effects of the aromatic par ts. There is no evidence for non-classical intercalation by partial in sertion between the nucleobases, nor for any intercalation of phenyl u nits.