Interactions Of Copper(Il) Porphyrins With DNA

R. F. Pasternack
Sean M. Ewen , '99
Ashwin L. Rao , '99
Aviva S. Meyer , '01
Miriam A. Freedman , '00
Peter J. Collings, Swarthmore College
S. L. Frey
M. C. Ranen
J. C. dePaula

Abstract

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)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)diphenylporphinecopper(II) (t-CuPagg), like the free-base t-H(2)Pagg 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 10(5)-10(6) 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-H(2)Pagg 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 (k(c)) is considerably smaller for t-CuPagg than for t-H(2)Pagg under comparable conditions, and that the template rigidity fosters assembly formation. We also report the resonance Raman spectra 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 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. (C) 2001 Elsevier Science B.V. All rights reserved.