Energy transfer processes leading to photocleavages

This type of DNA damages arises from an energy transfer between a triplet excited photosensitizer (porphyrin, metal complex, etc.) and an oxygen molecule, leading to the production of singlet oxygen (1O2).46,53

[Run(bpy)3]2+* + 3 O2 —> [ Run (bpy) 3 ]2+ + ^2*

Singlet oxygen is a very reactive species which may induce, among other processes, formation of oxidizing agents such as superoxide radicals (O2~, OOH') or hydroxyl radicals (OH'). These species are able to damage DNA, leading mainly to oxidation of the guanine moiety into 8-oxoguanine and to DNA cleavages.53 These cleavages have been demonstrated by gel electrophor-esis experiments with plasmid DNA. Indeed, a single strand break, in one of the two strands of the DNA double helix of a supercoiled closed circular form of plasmid DNA, causes its conversion into the open circular form which exhibits a different migration velocity on an agarose gel.

The area in which the generation of singlet oxygen by photosensitizers is applied in medicine in order to destroy cancer cells is called photodynamic therapy (PDT).54 Several hundreds of molecules have already been shown to photosensitize singlet oxygen production. In this context, polypyridyl RuII complexes are interesting due to, as mentioned above, their important absorption in the visible part of the spectrum and their long excited-state lifetimes. For

TT TT 1

example, the excitation of [RuII(bpy)3]2+ (Figure 19.6a) or [RuII(phen)3]2+ (phen = 1,10-phenanthroline) (Figure 19.6b) was shown to induce production of singlet oxygen and DNA single strand breaks.55 57 Rather high quantum yields of singlet oxygen production (from 0.1 to 1.0 depending on the complex and on the solvent) have been determined for different RuII complexes.56,58

Pauly and co-workers have recently shown that singlet oxygen production by the complex [RuII(bpy)2(phen)]2+ is able to block partially the activity of a bacteriophage RNA-polymerase.59 Moreno and co-workers have encapsulated the complex [RuII(dip(SO3Na)2)3]2+ (dip(SO3Na)2 = sodium salt of disulfonated 4,7-diphenyl-1,10-phenanthroline; Figure 19.6c) into polyacrylamide nanoparti-cles.60 They found that the polyacrylamide matrix does not quench the !O2* production, allowing it to reach the external solution and to react with a targeted molecule. These particles may be modified with tumor-recognizing groups and be used in photodynamic therapy. The main drawbacks of the in vivo treatments in photodynamic therapy are collateral damages to healthy cells, acquired resistance, and limitation of light penetration in tissues.60

SO,Na

Figure 19.6 Complexes that generate singlet oxygen. (a) [RuII(bpy)3]2+, (b) [RuII(phen)3]2+, (c) [RuII(dip(SO3Na)2)3]2+ (dip(SO3Na)2 = sodium salt of disulfonated 4,7-diphenyl-1, 10-phenanthroline)

SO,Na

Figure 19.6 Complexes that generate singlet oxygen. (a) [RuII(bpy)3]2+, (b) [RuII(phen)3]2+, (c) [RuII(dip(SO3Na)2)3]2+ (dip(SO3Na)2 = sodium salt of disulfonated 4,7-diphenyl-1, 10-phenanthroline)

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