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

• Published in: Inorganic chemistry 2012-12, Vol.51 (23), p.12669-12681
• Main Authors: Williams, Benjamin R, Dalton, Shannon R, Skiba, Meredith, Kim, Sung Eun, Shatz, Allison, Carroll, Patrick J, Burgmayer, Sharon J. Nieter
• Format: Article
• Language: English
• Subjects: Animals; Cattle; DNA - chemistry; DNA Cleavage; Ligands; Models, Molecular; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Photochemical Processes; Plasmids; Pteridines - chemistry; Pyridines - chemistry; Ruthenium - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/ic301219z

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)](PF6)2 1 is synthesized from ligand substitution of Ru(bpy)2Cl2 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)](PF6)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 1H 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)](PF6)2, [Ru(bpy)2(L-amino)](PF6)2, and [Ru(bpy)2(dppz)](PF6)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.