Interactions of copper(II) porphyrins with DNA

The interactions of three cationic water soluble copper(II) porphyrins, differing in peripheral substituents, with calf thymus DNA are described. Tetrakis(N-methylpyridinium-4-yl)porphinecopper(II) behaves as a simple intercalator under the conditions investigated, whereas tetrakis(4-N,N′,N″-trimethylanilinium)porphinecopper(II), binds externally, with some limited aggregation under high drug load conditions. In contrast, trans-bis(N-methylpyridinium-4-yl)diphenylporphinecopper(II) (t-CuPagg), like the free-base t-H2Pagg from which it is derived, is capable of forming extended electronically coupled arrays while bound to the DNA template. These arrays have been investigated using a combination of extinction spectroscopy, circular dichroism, RLS and resonance Raman spectroscopy. They are found to contain 105–106 porphyrin units, arranged in long, narrow organized structures. The kinetics of assembly of t-CuPagg is reported on three DNAs: ct DNA, poly(dG–dC)2 and poly(dA–dT)2. A non-conventional autocatalytic model first proposed for t-H2Pagg assembly formation is successful at fitting these data, permitting direct comparisons of kinetic parameters for the two porphyrins. It is found that the catalytic rate constant (kc) is considerably smaller for t-CuPagg than for t-H2Pagg under comparable conditions, and that the template rigidity fosters assembly formation. We also report the resonance Raman spectra of t-H2Pagg/ct DNA and t-CuPagg/ct DNA complexes. Aggregation on the DNA template changes the intensity pattern of the porphyrinʹs resonance Raman spectra, with some low- and high-frequency bands becoming strongly enhanced upon aggregation. We conclude that aggregation-enhanced resonance Raman spectroscopy is a useful probe of aggregation in porphyrin–DNA complexes that also gives detailed information about structural changes that accompany the aggregation process.