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

Abstract

The rigid dinuclear [(tap)(2)Ru(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(T(2)AG(3))(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(T(2)AG(3))(4).

Ru–TAP complexes and DNA: from photo-induced electron transfer to gene photo-silencing in living cells

“…As a function of increasing illumination times, the faster migrating adduct, giving the most intense spot after 3 min illumination, decreases in favour of the less migrating and finally non-migrating bands. The occurrence of covalent adducts with this telomeric sequence has been proven by nano-electrospray ionization analyses on the dialysed solution after illumination [46]. These analyses, complicated by the presence of a mixture of products, clearly showed the presence of photo-adducts corresponding to the addition of more than one complex on the telomeric sequence and indicated most probably the appearance of photo-cross-linked species inside the telomer.…”

Highly DNA‐Photoreactive Ruthenium 1,4,5,8‐Tetraazaphenanthrene Complex Conjugated to the TAT Peptide: Efficient Vectorization inside HeLa Cells without Phototoxicity – The Importance of Cellular Distribution

“…From selected structures from the preliminary MD simulations for noncovalent Ru-TAT/ODN complexes, the structures of the Ru-TAT-ODN covalent adducts were obtained as described previously. [46] The MD simulations of Ru-TAT and Ru-TAT-ODN were performed with the CHARMM force-field, [47] and water was considered explicitly through the use of the water box model. The MD simulations were performed in (N,V,T) at 300 K with a time step of 1 fs from 1 ns to 10 ns.…”

Studies of ruthenium(ii)-2,2′-bisimidazole complexes on binding to G-quadruplex DNA and inducing apoptosis in HeLa cells

“…Ruthenium(II) complexes have prominent DNA binding properties. 22 Thomas et al reported that the dinuclear tppz-based systems could bind with high affinity to quadruplex DNA at high ionic strengths through the 22-mer d(AG 3 3 ] human telomeric sequence. 16,17 Such complexes can tightly intercalate between the duplex DNA base pairs and stabilize the DNA.…”