Interactions of copper(Il) porphyrins with DNA

The interactions of three cationic water soluble copper(II) porphyrins, dif fering in peripheral substituents, with calf thymus DNA are described. Tetr akis(N-methylpyridinium-4-yl)porphin 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)d iphenylporphinecopper(II) (t-CuPagg), like the free-base t-H(2)Pagg from wh ich it is derived, is capable of forming extended electronically coupled ar rays while bound to the DNA template. These arrays have been investigated u sing a combination of extinction spectroscopy, circular dichroism, RLS and resonance Raman spectroscopy. They are found to contain 10(5)-10(6) porphyr in units, arranged in long, narrow organized structures. The kinetics of as sembly of t-CuPagg is reported on three DNAs: ct DNA, poly(dG-dC)(2) and po ly(dA-dT)(2). A non-conventional autocatalytic model first proposed for t-H (2)Pagg assembly formation is successful at fitting these data, permitting direct comparisons of kinetic parameters for the two porphyrins. It is foun d that the catalytic rate constant (k(c)) is considerably smaller for t-CuP agg than for t-H(2)Pagg under comparable conditions, and that the template rigidity fosters assembly formation. We also report the resonance Raman spe ctra of t-H(2)Pagg/ct DNA and t-CuPagg/ct DNA complexes. Aggregation on the DNA template changes the intensity pattern of the porphyrin's resonance Ra man spectra, with some low- and high-frequency bands becoming strongly enha nced upon aggregation. We conclude that aggregation-enhanced resonance Rama n spectroscopy is a useful probe of aggregation in porphyrin-DNA complexes that also gives detailed information about structural changes that accompan y the aggregation process. (C) 2001 Elsevier Science B.V. All rights reserv ed.