Controlling with light the interaction betweentrans-tetrapyridyl ruthenium complexes and an oligonucleotide

Abstract

Three new trans-ruthenium(ii) complexes coordinated to tetrapyridyl ligands, namely [Ru(bapbpy)(dmso)Cl]Cl ([2]Cl), [Ru(bapbpy)(Hmte)](PF) ([3](PF)), and [Ru(biqbpy)(Hmte)](PF) ([4](PF)), were prepared as analogues of [Ru(biqbpy)(dmso)Cl]Cl ([1]Cl), a recently described photoactivated chemotherapy agent. The new complexes were characterized, and their crystal structures showed the distorted coordination octahedron typical of this family of complexes. Their photoreactivity in solution was analyzed by spectrophotometry and mass spectrometry, which showed that the sulfur ligand was substituted upon blue light irradiation. The binding of the ruthenium complexes to a reference single-stranded oligonucleotide (s(CTACGGTTTCAC)) was explored both in the dark and under light irradiation by gel electrophoresis and high-resolution mass spectrometry. While adduct formation in the dark was negligible for the four complexes, light irradiation led to the formation of adducts with one or two ruthenium centers per oligonucleotide. The absence of interactions in the dark and the presence of complex-oligonucleotide adducts demonstrate that visible light controls the interaction of these ruthenium complexes with nucleic acids.

Ru(II) Compounds: Next-Generation Anticancer Metallotherapeutics?

“…137,138 Very recent work has been reported about interaction between Ru(II) trans-tetrapyridyl ruthenium therapeutic and an oligonucleotide controlled by light irradiation. 139 The strategy of using Ru(II)-photocaged therapeutics has been denoted in several recent studies in the literature that associate a drug with a complex to the superior restraint of the biological action and release of the drug in selected tissues using light. 140−142 Abiraterone is an inhibitor of cytochrome P450 17A1 inhibitor (CYP17A1), useful in metastatic prostate cancer therapy.…”

“…The chemical compounds for this technique exhibit light-activated characteristics and are referred to as photoactivated chemotherapy agents. , The mechanism of action of these agents is based on the ligand exchange to create metal centers able to form DNA adducts or photorelease of a bioactive compound. , Ligand exchange plays a vital part in PACT. Glazer et al denoted antitumor Ru­(II) compounds bearing methylated bipyridyl, pyridylbenzazole ligands and their photochemical and photobiological action. , Very recent work has been reported about interaction between Ru­(II) trans-tetrapyridyl ruthenium therapeutic and an oligonucleotide controlled by light irradiation …”

<p>Ruthenium Complexes as Anticancer Agents: A Brief History and Perspectives</p>

“…Porfimer sodium (Photofrin), 107 aminolevulinic acid (ALA), 108 and methyl ester of ALA (Metvixia) 109 have been approved for clinical practice as photosensitizing agents by the FDA. In contrast, PACT 65,[110][111][112] utilizes light to induce activation of the internalized prodrug moiety independent of the presence of oxygen inside cells. Thus, PACT is an attractive approach to treat tumors in a hypoxic condition, which is the notorious characteristic of solid cancers.…”

Synthesis and Biological Screening of New 4‐Hydroxycoumarin Derivatives and Their Palladium(II) Complexes

“…Besides, numerous complexes of ruthenium, gold, and palladium with noncoumarin ligands such as terpyridine, tetrapyridine, and 1,10-phenanthroline, ligands are known to occupy a significant place in cytotoxic research [20][21][22][23].…”