engleski

New porphyrin-nucleobase hybrid compounds and their interaction with nucleosides and nucleic acids

Four new porphyrin derivatives are described: one (1) with a methoxyphenyl group and three pyridinium units (for comparison only), and three others with either adenine (2, 3) or thymine (4) bases. The synthetic strategies vary from known literature procedures in that the methylation of pyridinium subunits takes place before the formation of the hybrid molecule, beginning with simultaneous condensation of pyridinealdehyde and 3-(propionyloxy)benzaldehyde, with subsequent chromatography under improved conditions. The thymine derivative 4 is obtained from trimethylated tetrapyridylporphyrin T4PyP by treatment with a suitable thymine-alkyl bromide. Dilution experiments in water show the absence of intermolecular porphyrin associations under the experimental conditions used. UV and NMR spectroscopic data indicate strong intramolecular self -stacking between the porphyrin moiety and the covalently attached nucleobases. This results in smaller affinities of porphyrin-nucleobase conjugates towards added nucleosides than observed with the reference compounds tris- or tetrakis-pyridinium porphyrin (I and TMPyP, respectively). Compounds 2-4 displayed no significant discrimination between A and T based on complementarity of nucleobases, which is explained by the strong competition from bulk water with Watson-Crick hydrogen bonds. Interactions of ligands 1-4 with ct DNA and ss-RNA polynucleotides were studied by fluorimetric and UV/Vis titration. In most cases the fluorescence of 1-4 was first quenched by addition of polynucleotide at porphyrin/polynucleotide ratios (r) close to saturation of intercalation binding sites, and then enhanced at ratios r < 0.1. The changes at r > 0.1 were attributed to intermolecular association of porphyrins along the polynucleotide groove, while the changes observed at large excess of intercalation binding sites (r much less than 0.1) indicate intercalation of porphyrin into the polynucleotide. Scatchard analyses at r much less than 0.1 are in most cases in line with the formation of only 1:1 complexes. With poly U the non-complementary compounds I and 4 showed only increased fluorescence, while the complementary compounds 2 and 3 showed decreases as well as increases. Addition of poly U to 2 and 3 induced strong bathochromic shifts of the Soret bands, characteristic of intercalation. Although no affinity difference between complementary and non-complementary complexes of 2-4 and ss-polynucleotides was observed, significant differences in emission changes in poly U titrations suggest specific interactions of the adenine conjugates 2 and 3.

Nucleic acids. Nucleotides; Porphyrinoids; Supramolecular chemistry.

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