Mechanism of DNA Damage Photosensitized by Trisbipyrazyl Ruthenium Complex. Unusual Role of Cu/Zn Superoxide Dismutase¶

Abstract

Trisbipyrazyl ruthenium(II) (Ru[bpz]3(2+)) was examined as DNA photosensitizer. Damage resulting from the photolysis of synthetic oligonucleotides has been monitored by polyacrylamide gel electrophoresis. Photoadduct formation is found on both single- and double-stranded oligonucleotides. On oligonucleotide duplex, oxidative damage occurs selectively at the 5'G of the 5'GG3' site and to a lesser extent at the 5'G of a GA sequence. These findings suggest the involvement of electron transfer and show that this mechanism is the main DNA damaging process involved in Ru(bpz)3(2+) photosensitization. In addition, photoadducts and oxidative damage are both highly affected by an increase of salt concentration in the reaction medium, stressing the importance of direct interactions between nucleic acid bases and the excited ruthenium complex for efficient electron transfer. On single-stranded oligonucleotides, all the guanines are oxidized to the same extent. In this case, oxidative damage, which is not affected by an increase of salt in the solution, has been attributed, in part, to singlet oxygen. More importantly, Cu/Zn superoxide dismutase (SOD) strongly enhances the yield of all damage, correlated to an increase of both electron transfer and singlet oxygen production. This original activity of SOD is the first example of bioactivation of a polyazaaromatic ruthenium complex.

Photoinduced Interactions of Supramolecular Ruthenium(II) Complexes with Plasmid DNA: Synthesis and Spectroscopic, Electrochemical, and DNA Photocleavage Studies

“…This dual mechanism has been observed for monometallic tris(bipyrazyl)ruthenium(II). 63 The increase in photonicking in the presence of the singlet oxygen scavenger sodium azide suggests that superoxide plays a more significant role in the photonicking. If the presence of singlet oxygen somehow interferes with the superoxide radical, then upon removal of the singlet oxygen, it would be expected that photonicking would be enhanced.…”

Ru(II) complexes and light: molecular tools for biomolecules

“…In connection with 'the consequences of the photo-electron transfer' , the results of a study of a photo-oxidizing complex in the presence of a protein are worthwhile to be mentioned. [43,97,98] The behaviour of the complex [Ru(bpz) 3 ] 2þ has been investigated in the presence of the Cu/Zn superoxide dismutase protein (Cu/ Zn SOD) ( Fig. 7).…”

Photooxidation of Guanine by a Ruthenium Dipyridophenazine Complex Intercalated in a Double‐Stranded Polynucleotide Monitored Directly by Picosecond Visible and Infrared Transient Absorption Spectroscopy

“…[11][12][13][14][15] As such electron transfers are fast chemical processes, they are usually initiated by short laser-pulse excitation of sensitizers such as phenothiazonium dyes, [16,17] anthraquinones [18,19] or metal complexes. [20][21][22][23][24] The study of compounds intercalated into DNA is especially appropriate for theoretical treatment as the relative orientation of the electron donor and acceptor is well defined.…”