Synthesis of the DNA−[Ru(tpy)(dppz)(CH₃CN)]²⁺ Conjugates and Their Photo Cross-Linking Studies with the Complementary DNA Strand

Abstract

We here report our studies on the conjugation of photoreactive Ru 2+ complex to oligonucleotides (ODNs), which give stable duplex with the complementary target DNA strand. These functionalized DNA duplexes bearing photoreactive Ru 2+ complex can be specifically photolyzed to give the reactive aqua derivative, [Ru(tpy)(dppz)(H 2 O)] 2+ -ODN, in situ, which successfully cross-links to give photoproduct(s) with the target DNA strand in a sequence specific manner. Thus, the stable precursor of aqua-ruthenium complex, monofunctional polypyridyl ruthenium complex:[Ru(tpy)(dppz)(CH 3 CN)] 2+ (tpy = 2,2':6',2''-terpyridine, dppz = dipyrido[3,2-a:2',3'-c]phenazine), has been site-specifically tethered to ODN, for the first time, both by solid phase synthesis and post- Table 1). This shows that with the rigidly packed structure, as in the duplex with middle-Ru 2+ ODN, the metal center flexibility is considerably reduced, and consequently the accessibility of target G residue by the aquaruthunium moiety becomes severely restricted, which results in a poor yield in the cross-coupling reaction. The crosslinked product was characterized by PAGE, followed by MALDI-TOF MS.

New Functional Polymers and Materials Based on 2,2′:6′,2″‐Terpyridine Metal Complexes

“…19) can be specifically photolyzed to give a reactive aqua derivative, which can then form a duplex with a DNA target 11mer. [61] This duplex was found to be significantly more stable than the natural, non-Ru II complex containing a DNA±DNA duplex. Following the hybridization of the ODN with the DNA, the nitrogen of a guanine completes the octahedral coordination sphere of the mixed ruthenium(II) complex.…”

Synthesis, Structure, and Redox Properties of a trans-Diaqua Ru Complex That Reaches Seven-Coordination at High Oxidation States

“…1 These complexes have a myriad of applications in many fields including, photochemistry and photophysics, 2,3 bioinorganic chemistry 4,5 and catalysis. 6,7 From a catalytic perspective, Ru complexes are active in a large number of reactions involving C-C coupling, 6 C-H insertion and especially in redox catalysis with organic transformations.…”

Photoadducts of Metallic Compounds with Nucleic Acids − Role Played by the Photoelectron Transfer Process and by the TAP and HAT Ligands in the RuII Complexes

“…When these Ru complexes are photolysed, the Cl Ϫ ligand is easily substituted by a H 2 O molecule, which leads to the aquaruthenium complex. This latter complex, like the Rh species, is reactive towards the DNA bases and forms a coordination bond with a heterocyclic nitrogen atom [22] of a nucleobase. The covalent binding of such aqua Ru complexes to DNA has been demonstrated by ultrafiltration, extensive dialysis and ethanol precipitation.…”

“…[23,24] However, the reaction between [Ru(tpy)(X)(H 2 O)] 2ϩ and double-stranded DNA proceeds with a rather poor yield ([Ru] bound /[DNA-nucleotide] is approximately 0.02) because of the important steric hindrance due to the presence of the polypyridyl (X) ligands and the incoming reactive DNA base. [22] …”

“…(ii) On the other hand, oligonucleotide conjugates bearing a Ru II complex such as [Ru(tpy)(dppz)(CH 3 CN)] 2ϩ (tpy ϭ 2,2Ј:6Ј,2ЈЈ-terpyridine) [22] have also been tested. This complex, chemically attached to a probe sequence, can lead to successful crosslinkings with the complementary sequence.…”