Pteridine Cleavage Facilitates DNA Photocleavage by Ru(II) Polypyridyl Compounds

Abstract

The synthesis, characterization, binding to calf thymus DNA, and plasmid DNA photocleavage studies of two ruthenium(II) pteridinylphenanthroline complexes are reported where the new pteridinylphenantholine ligands in these complexes are additions to a larger family designed to resemble DNA bases. [Ru(bpy)(2)(L-keto)](PF(6))(2)1 is synthesized from ligand substitution of Ru(bpy)(2)Cl(2) by 4-keto-pteridino[6,7-f]phenanthroline (L-keto). Increasing the reaction temperature during synthesis of 1 causes a ring scission of the L-keto ligand within the pyrimidine ring yielding a second Ru complex, [Ru(bpy)(2)(L-aap)](PF(6))(2)2 where L-aap is 2-amino-3-amidopyrazino[5,6-f]phenanthroline. The ring cleavage reaction is accompanied by the loss of one carbon in the pyrimidine ring. Complexes 1 and 2 are characterized by (1)H NMR, UV/visible absorption and FT-IR spectroscopies and by cyclic voltammetry, and these results are presented in comparison to the previously reported related complexes [Ru(bpy)(2)(L-allox)](PF(6))(2), [Ru(bpy)(2)(L-amino)](PF(6))(2), and [Ru(bpy)(2)(dppz)](PF(6))(2). In addition, 2 has been structurally characterized by X-ray diffraction. Both 1 and 2 are good intercalators of calf thymus DNA as determined by viscometry and binding constants obtained from absorption titrations. Only the ring-cleaved complex 2 exhibits a high degree of pBR322 plasmid photocleavage in contrast to the other pteridinyl-phenanthroline complexes, which exhibit no plasmid DNA photocleavage. Complex 1, however, decomposes in buffer forming the photocleaver 2, demonstrating that sample age and reactivity can affect observed photocleavage. Complex 2 appears to photocleave DNA through a singlet oxygen mechanism.

Synthesis, DNA binding mode, singlet oxygen photogeneration and DNA photocleavage activity of ruthenium compounds with porphyrin–imidazo[4,5‐f]phenanthroline conjugated ligand

“…The reason for this was probably due to the introduction of ‘relaxed’ metal into the porphyrin to stimulate the triplet state, which prevented the bimolecular quenching by oxygen . However, Por 2 could also produce 1 O 2 to a smaller extent, which may be attributed to the hydrophilic part of the Ru–phenanthroline complex, as some types of Ru complex also have a certain photodynamic activity …”

Theoretical studies on interaction properties of chiral Ru(II) polypyridyl complexes with DNA

“…Therefore, complexes 1 cleave DNA by the quite active singlet oxygen [27,28] and mainly performs a singlet oxygen photosensitization mechanism. Under light irradiation, Ru(II) polypyridyl complexes are easily excited and undergo an intramolecular electron transfer, and thus the excited-state complexes can rapidly react with oxygen molecules around to produce the quite active singlet oxygen.…”

Interaction of metal complexes with nucleic acids

“…In a different study, complexes [Ru(bpy) 2 (L-keto)] 2+ and [Ru(bpy) 2 (L-aap)] 2+ have been shown to be good intercalators of CT-DNA. 40 The latter exhibits an unusually high ability to photocleave pBR322 plasmid under aerobic conditions. This was suppressed upon addition of azide -a singlet oxygen scavenger -or when the reaction was carried out under anaerobic conditions.…”