Photochemotherapy

Photochemotherapy has been revealed to kill tumor cells most frequently by inactivating nucleic acids. However, the interaction of photosensitizers with serum proteins, annexins, etc., can also be important. The [Rh(phen)2(phi)]3+ complex (Figure 20.5) binds selectively to DNA duplexes by intercalation into the major groove but shows no detectable interaction with A-conformational RNA duplexes. However, the RNA folds of bovine (BIV) and human (HIV) immunodeficiency viruses have remarkable structures in which intramolecular base triples are formed and the major grooves are widened. At these sites, transcription is activated. The [Rh(phen)2(phi)]3+ complex targets sites of triple base interactions which are cleaved upon photoactivation. The primary site cleaved upon photoactivation in the BIV by the rhodium complex is U24, a base participating in the novel base triple with A13 and U10 bases.100 The A-[Rh(phen)2(phi)]3+ complex binds to this site with an affinity of 2 x 106 M"1. Thus, the rhodium complex is able to compete for RNA target with the BIV trans-activating (Tat) peptide.100

A rhodium complex, rac-[Rh(bpy)2(phzi)]3+ (phzi = Benzo[a]phenazine-5,6-quinone diimine), intercalates as a sterically demanding intercalator to destabilized mismatched sites in double-helical DNA and, upon photoactivation, promotes direct strand scission at single base mismatch sites.101 Unlike the [Rh(bpy)2(chrysi)]3+ complex, the phzi complex intercalates and cleaves with a high affinity and efficiency. The specific binding constants for CA, CC and CT mismatches are 0.3, 1 and 6 x 107M"\ respectively. «'s-[RhCl2(phen)2]+ and related complexes, in photochemically induced reactions, can form covalent bonds with calf-thymus DNA, nucleotides and nucleosides.102 The cis-[RhCl2(phen)2]+ and cis-[RhCl2(phen)(phi)]+ complexes form, upon photoexcitation (320-400 nm), cross-inks in nucleic acids through the involvement of purines.103 The former complex, despite the negligible absorption beyond the 320 400 nm region, when irradiated with red light, populates a highly reactive excited state that forms covalent bonds with DNA.104 A series of [Rh2(RCOO)4] complexes (R = H, Me, Et, CF3) was examined for enhancement of efficiency of X-ray-induced killing of Salmonella typh'mun'um.105,106 A range of cis-Pt(II) and [Rh2(RCOO)4] complexes have been examined for their ability to increase the radiation sensitivity of aerobic and hypoxic V-79 cells in vitro. The platinum complexes show considerably smaller levels of sensitization than rhodium(II) carboxylates.107

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