Photodynamic therapy (PDT) is a cancer treatment method in which a photosensitizer, light of a particular wavelength, and also oxygen are used to destroy cancerous cells. Cancer cells absorb the photosensitizing agent which is injected into the body, and it is triggered to cause cell destruction upon absorption of light. This occurs because of the excitation of the photosensitizer produces reactive oxygen species that induce a cascade of cellular and molecular events in the body. Photosensitizing agents that can photo-cleave DNA at long wavelengths are highly demanded in PDT, because the long wavelengths of light can penetrate through tissue deeply compared to visible light. While most of the photosensitizers are activated at wavelengths less than 690 nm, penetration of light continues to increase at increasing wavelengths. In this thesis, photosensitizers that can be activated to oxidize DNA with long wavelengths of light will be discussed. Using quinoline cyanine dyes, here we report the first example of DNA photocleavage at a wavelength of light above 800 nm.

Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis-thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at ∼80 nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors.

The molecular identity of the green emission of polyfluorene is investigated in the view point of the molecular interactions between modeled segments. The semi-empirical quantum methods, ZINDO/S and AM1 (AM1-CIS), are used in combination to provide reasonable explanations for experimental spectroscopic properties of monodisperse fluorene oligomers and fluorene oligomers with a central keto defect in dilute solutions. Applying the same method, the molecular interactions between model segments are found to exist and are significant. However, the spectroscopic property change from the molecular interactions is negligible. In addition, the effects of mechanical stress and multi-defects on fluorene oligomers are investigated. On the other hand, the redox mechanisms proposed for the oxidation of an amphiphilic cyanine (C8S3) J-aggregates immobilized at ITO electrode and the subsequent dehydrogenated dimmer formation during cyclic voltammetry based on analysis of absorption spectra during the process are verified with the combined semi-empirical quantum methods similar to the previous methods. The absorption spectra assigned by experiment for electrochemical species involved in the proposed mechanism show reasonable match to the theoretically estimated absorption energies of the corresponding simplified model systems. In addition, the standard reduction potentials of the fairly large molecules, C8S3 monomer and its dehydrogenated dimer, are pursued with quantum mechanical calculations. The free energy difference between the oxidized and reduced states of the target systems is decomposed to electronic energy, solvation energy and temperature-dependent free energies terms. Based on AM1 ground state geometries and with the corresponding temperature dependent free energies, the electronic energies and the solvation energies are each evaluated by two different methods. The electronic energies are calculated with AM1 method and DFT calculation and, also, the solvation energies are obtained based on the atomic partial charges from AM1 and DFT wavefunctions with continuum dielectric solvent approximation. The four calculation schemes from the combinations of the electronic and solvation energy estimation methods are tested with the redox compounds with various molecular weights and the estimations are compared with the corresponding experimental redox potentials. The relative redox potentials between two different redox systems are found to be reasonably estimated with the four calculation schemes. / text

Cyanine dyes that absorb light in the near infrared to far red region of the electromagnetic spectrum are desirable as photosensitizers for photodynamic cancer therapy. Light of wavelengths in this range is able to deeply penetrate tissue allowing for practical in vivo use of these dyes. A series of three structurally similar pentamethine cyanine dyes that absorb light ~800 nm to ~500 nm was tested to determine the effects of structural influences on the yields of supercoiled DNA photo-converted to nicked or linear forms. Possible mechanisms and optimal parameters for near- quantitative DNA photocleavage with a symmetrical quinoline pentamethine cyanine dye are discussed.

Cyanine dyes are attractive photosensitizers for photodynamic therapy due to their ease of structure modification and intense absorption in the near-infrared range. Photosensitizers that can bind to DNA and absorb at long enough wavelengths of light to deeply penetrate biological tissue are in high demand for treatment of cancer and other diseases. The following study analyzes the DNA interactions of three pentamethine cyanine dyes with very similar structures, all of which absorb light at wavelengths longer than 800 nm. The work described involves an extensive study of the photocleavage abilities and DNA binding characteristics of these dyes. Our lead compound was a bromophenyl meso substituted symmetrical quinoline cyanine dye. Spectroscopic data, gel electrophoresis experiments and other studies were used to provide evidence of DNA binding mode, ROS production, and of dye-sensitized DNA photocleavage at the unprecedented wavelength of 850 nm.

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