RESUMEN
An octahedral rhodium complex (cis-dichloro(dipyrido[3,2a-2',3'c]phenazine)(1,10-phenanthroline)rhodium(III) chloride; DPPZPHEN) has been prepared that can penetrate tumor cell membranes and the Sindbis viral capsid. The compound is phototoxic to these entities when irradiated with UVA light. Model studies with calf thymus and supercoiled plasmid DNA indicate that the complex can both bind with, and nick, nucleic acid. Analysis of Sindbis virus, following irradiation with the metal complex, confirmed that the viral genome was rendered noninfectious by this treatment.
Asunto(s)
Daño del ADN , Compuestos Organometálicos/síntesis química , Rodio/química , Virus Sindbis/efectos de la radiación , Rayos Ultravioleta , Animales , Bovinos , Compuestos Organometálicos/farmacología , Fotólisis , Plásmidos/efectos de la radiación , Timo/efectos de la radiación , Células Tumorales CultivadasRESUMEN
We have extended our study of the decomposition of urocanic acid (UCA) with ultraviolet A radiation (UV-A) by the self-sensitized generation of singlet oxygen (see Photochem. Photobiol. 75, 565 [2002]). The chemistry has been found to be partially dependent on the presence of trace metal, most likely iron. Rigorous removal of metal impurities from the reaction mixture, using Chelex, retarded (but did not eliminate) the UV-A-initiated UCA degradation. The addition of small amounts of ferric chloride to the Chelex-treated solutions restored reactivity. Chelex treatment had a modest effect on the previously reported ability of UCA photoproducts to photonick supercoiled plasmid DNA. Also, photoinactivation of Sindbis virus on irradiation with the UCA photoproducts is now reported. Inactivation of the virus by a photoproduct mixture derived from a UCA solution that had been pretreated with Chelex was less rapid and gave better behaved time-course plots than was observed for photoproducts from non-Chelex treated solutions. These results are particularly noteworthy in light of the ubiquitous presence of both UCA and iron in the skin.
Asunto(s)
Especies Reactivas de Oxígeno/síntesis química , Oligoelementos/química , Rayos Ultravioleta , Animales , Daño del ADN , Histidina/química , Humanos , Modelos Biológicos , Fotoquímica/métodos , Plásmidos/química , Piel/química , Superóxidos/química , Ácido Urocánico/química , Ácido Urocánico/efectos de la radiación , Activación Viral/efectos de la radiaciónRESUMEN
Singlet oxygen-initiated decomposition of urocanic acid (UCA) (3-(1H-imidazol-4(5)-yl)-2-propenoic acid) was used to successfully confirm the report that UCA generates singlet oxygen when irradiated with ultraviolet A light (UVA). 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. Some nicking of the phiX-174 supercoiled plasmid DNA was observed when UCA was irradiated with UVA to complete destruction of the starting material, and the product mixture was then mixed with the plasmid in the dark. More extensive nicking was seen when the photoproduct mixture and the plasmid were irradiated with UVA light. An "aged" (4 days) solution of UCA photoproduct no longer caused nicking in the dark but retained the capability to nick the plasmid when irradiated. There is evidence for the presence of hydroperoxides in the UCA photolysis product mixture, and the quenching studies with 2-propanol indicate that free radicals are involved in the plasmid-nicking photochemistry. Singlet oxygen does not appear to play a role in the nicking of the plasmid.