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 thyminealkyl 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 (1 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