A Rigid Dinuclear Ruthenium(II) Complex as an Efficient Photoactive Agent for Bridging Two Guanine Bases of a Duplex or Quadruplex Oligonucleotide

• Published in: Chemistry : a European journal 2010-04, Vol.16 (13), p.3951-3961
• Main Authors: Rickling, Stéphane, Ghisdavu, Liana, Pierard, Frédéric, Gerbaux, Pascal, Surin, Mathieu, Murat, Pierre, Defrancq, Eric, Moucheron, Cécile, Kirsch-De Mesmaeker, Andrée
• Format: Article
• Language: English
• Subjects: Adducts; Anisotropy; Base Sequence; Bridging; Chemical Sciences; Chemistry; Cross-Linking Reagents - chemistry; DNA; DNA - chemistry; Electrophoresis; Guanine - chemistry; Guanines; Illumination; Ligands; Mass Spectrometry; Molecular Structure; N ligands; Nucleic Acid Conformation; oligonucleotides; Oligonucleotides - chemistry; Organometallic Compounds - chemistry; Photochemistry; ruthenium; Ruthenium - chemistry; Separation; Strands
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200902817

The rigid dinuclear [(tap)2Ru(tpac)Ru(tap)2]4+ complex (1) (TAP=1,4,5,8‐tetraazaphenanthrene, TPAC=tetrapyridoacridine) is shown to be much more efficient than the mononuclear bis‐TAP complexes at photodamaging oligodeoxyribonucleotides (ODNs) containing guanine (G). This is particularly striking with the G‐rich telomeric sequence d(T2AG3)4. Complex 1, which interacts strongly with the ODNs as determined by surface plasmon resonance (SPR) and emission anisotropy experiments, gives rise under illumination to the formation of covalent adducts with the G units of the ODNs. The yield of photocrosslinking of the two strands of duplexes by 1 is the highest when the G bases of each strand are separated by three to four base pairs. This corresponds with each Ru(tap)2 moiety of complex 1 forming an adduct with the G base. This separation distance of the G units of a duplex could be determined thanks to the rigidity of complex 1. On the basis of results of gel electrophoresis, mass spectrometry, and molecular modelling, it is suggested that such photocrosslinking can also occur intramolecularly in the human telomeric quadruplex d(T2AG3)4. Photoactive agents: The dinuclear [(tap)2Ru(tpac)Ru(tap)2]4+ (TAP= 1,4,5,8‐tetraazaphenanthrene, TPAC= tetrapyridoacridine) complex is very efficient at photobridging two guanine (G) bases (see illustration), in which either each base belongs to a strand of a duplex, or both bases belong to a single strand of a telomeric sequence. In the duplex, the highest photocrosslinking yield occurs when the G units are separated by a distance corresponding to three to four base pairs.