Photochemistry and phototoxicity of naturally occurring and synthetic chemicals

Part A of this thesis describes the preparation of the rhodium bisbipyridyl complex, cis-dichloro(dipyrido[3,2a-2′3′ c]phenanzine, 1,10-phenanthroline) rhodium(III) chloride, (DPPZPHEN). DPPZPHEN associates strongly with DNA in the dark (Keq = 3.4 × 105 M−1). Upon irradiation DPPZPHEN covalently binds to calf thymus DNA, and photonicks &phis;X-174 DNA plasmid. DPPZPHEN photoinactivates Sindbis virus with \u3e6 logs of photosensitized virus inactivation at a rate of 2.4 × 10−19 photons−1 . DPPZPHEN inactivation of virus, and the nicking of plasmid proceed without formation of reactive diffusable species. RNA from Sindbis virus that had been irradiated with DPPZPHEN is no longer infective, a confirmation that nucleic acid is a target for the photoactivated metal complex. In addition, DPPZPHEN is phototoxic to KB, GN4, and M109 carcinoma cells. In part B of the thesis, singlet oxygen-initiated decomposition of UCA was used to successfully confirm the report that UCA generates singlet oxygen when irradiated with UVA light. The UCA generated singlet oxygen converts UCA to one or more products that then catalyze the further destruction of the UCA with UVA light by singlet oxygen formation. Free radicals are also involved in the oxidative degradation of UCA with UVA light. These radicals are possibly formed by a combination of the photodecomposition of peroxides and Fenton-like chemistry. The latter is evidenced by the dependency of the photochemistry on the presence of trace metals, most likely iron. Photonicking of &phis;X-174 plasmid DNA and inactivation of Sindbis virus were observed when UCA was irradiated with UVA light to complete destruction of the starting material and the product mixture further irradiated with virus or plasmid DNA. The nicking of the plasmid occurs mainly through the formation of free radicals, as evidenced by quenching studies. Singlet oxygen does not seem to play a role in plasmid nicking. The presence of trace metal in solution affected the photonicking of plasmid DNA and the photoinactivation of virus