[Synthesis and characterization of model system in biological related function--model compounds for investigation of metal-metal interaction and nucleobase-aromatics interaction].
Several kinds of compounds available as model systems to investigation on metal-metal interaction in metalloproteins and on interaction of aromatics with nucleobases in arene intercalation to DNA were synthesized and characterized by spectrometry. Double and triple layered porphyrinophanes linked with 1,1'- or 1,3-disubstituted ferrocene moieties and their iron and cobalt complexes were prepared. Stabilities of their oxygenation complexes depended on bridging mode, lengths of alkyl linkers, distance between metals, and feature of hydrophobic cavity. Ferrocenophane derivatives in which nucleobase and aromatic hydrocarbon (naphthalene or anthracene) moieties substituted to their cyclopentadienyl rings in a stacking mode between the two chromophores were synthesized, as a model system of intercalation of aromatic condensed-ring hydrocarbons to DNA. Characterization of the ferrocenophanes by spectrometry and molecular modeling suggested that these chromophores interacted due to NH-pi hydrogen bonding and pi-pi charge transfer. A number of porphyrin derivatives covalently connected with a nucleobase or a nucleobase pair in a face-to-face mode between the porphyrin and nucleobase moiety were synthesized. The spectroscopic behavior of the derivatives indicate a greater affinity of the guanine-cytosine pair for porphyrin in comparison with the adenine-thymine pair. These results are compatible with the already reported spectroscopic and kinetic properties of mixing system of DNA and porphyrin derivatives. Moreover, the fluorescence spectra of the nucleobase-porphyrin derivatives gave a piece of evidence to cause DNA cleavage by photosensitizer via "type I" mechanism, in which direct action of singlet or triplet state of photosensitizer excited by laser irradiation brings about damage of cell or DNA.
Hisatome
M
M
Faculty of Pharmaceutical Sciences, Science University of Tokyo, 12 Ichigaya-Funagawara, Shinjuku-ku, Tokyo 162-0826, Japan.
D004249:DNA Damage; D004347:Drug Interactions; D017324:Hematoporphyrin Derivative; D006801:Humans; D008670:Metals; D008956:Models, Chemical; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D009705:Nucleosides / Q000138:chemical synthesis; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011084:Polycyclic Aromatic Hydrocarbons; D011166:Porphyrins / Q000138:chemical synthesis
D008670:Metals; D009705:Nucleosides; D017319:Photosensitizing Agents; D011084:Polycyclic Aromatic Hydrocarbons; D011166:Porphyrins; D017324:Hematoporphyrin Derivative