Interactions Of Porphyrins With Nucleic Acids

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The interactions of nucleic acids with water-soluble porphyrins and metalloporphyrins have been investigated by stopped-flow and temperature-jump techniques. Both natural DNA (calf thymus) and synthetic homopolymers [poly(dG-dC) and poly(dA-dT)] have been employed. The porphyrins studied belong to the tetrakis(4-N-methylpyridyl)porphine (H₂TMpyP-4) series and can be divided into two groups: (I) those which have no axial ligands when bound to nucleic acids [e.g., Ni(II), Cu(II), and the nonmetallic derivatives] and (II) those which maintain axial ligands upon binding [e.g., Mn(III), Fe(III), Co(III), and Zn(I1) derivatives]. The reaction of both axially and nonaxially liganded porphyrins at AT sites is too rapid to be measured by the kinetic methods utilized, whereas at GC sites the interaction of the nonaxially liganded porphyrins is in the millisecond time range and can be monitored by both stopped-flow andtemperature-jump techniques. These results corroborate previous static studies, utilizing visible spectroscopy and circular dichroism, which indicate that the formation of an intercalated complex occurs only at GC base pair sites with porphyrins which do not possess axial ligands. With all the porphyrins investigated, the complexes formed at AT sites are envisioned as being of an "external" type involving some degree of overlap between the porphyrin and the bases of the duplex. In relaxation experiments of poly-(dG-dC) with H₂TMpyP-4, a large, reproducible effect is observed which can be analyzed as a single exponential. Rate constants for association and dissociation of the H₂TMpyP-4/poly(dG-dC) complex are 3.7 X 10⁵ M−¹ s−¹ and 1.8 s−¹, respectively. Relaxation studies of mixtures of poly(dA-dT) and poly(dG-dC) with H₂TMpyP-4 indicate that the transfer of the porphyrin from one homopolymer to another occurs via a mechanism involving dissociation rather than direct transfer. With calf thymus DNA and H₂TMpyP-4, a multiphasic relaxation profile is observed. Both the amplitude and concentration dependencies of these kinetic effects indicate that the processes being observed involve the redistribution of porphyrin among the various sites on the polynucleotide. A comparison of the relaxation times obtained for this system with those obtained for mixtures of the synthetic homopolymers with H₂TMpyP-4 strongly suggests that, for the natural system, the porphyrin can move from site to site without first dissociating into the solvent medium.

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