Photo‐Oxidizing Ruthenium(II) Complexes with Enhanced Visible‐Light Absorption and G‐quadruplex DNA Binding Abilities

Abstract

Photosensitizers that gather high photo‐oxidizing power and strong visible‐light absorption are of great interest in the development of new photo‐chemotherapeutics. Indeed, such compounds constitute attractive candidates for the design of type I photosensitizers that are not dependent on the presence of oxygen. In this paper, we report on the synthesis and studies of new ruthenium(II) complexes that display strong visible‐light absorption and can oxidize guanine residues under visible‐light irradiation, as evidenced by nanosecond transient absorption spectroscopy. The reported compounds also tightly bind to G‐quadruplex DNA structures from the human telomeric sequence (TTAGGG repeat). The kinetic and thermodynamic parameters of the interaction of these Ru(II) complexes with G‐quadruplex and duplex DNA were studied thanks to luminescence titrations and bio‐layer interferometry measurements, which revealed higher affinities towards the non‐canonical G‐quadruplex architecture. Docking experiments and non‐covalent ionic analysis allowed us to gain information on the mode and the strength of the interaction of the compounds towards G‐quadruplex and duplex DNA. The different studies emphasize the substantial influence of the position and the number of non‐chelating nitrogen atoms on the interaction with both types of DNA secondary structures.

Iridium(iii)-based minor groove binding complexes as DNA photocleavage agents

“…[93][94][95] For these reasons, methods to selectively bind to telomeric quadruplexes [96][97][98][99] and/or shorten telomere length in cancer cells have been investigated. 27,59,[100][101][102][103] Given that such studies have included transition metal complexes as binding substrates, 25,104 and previous work within the Thomas group has identified Ru II complexes that bind to quadruplex-folded human telomere sequence (HTS) with high affinities, 21,22,105,106 analogous experiments were carried out with 1 and 2. These were of particular interest as a very recent report from the Keyes group 107 has shown that a Ru II -complex containing a ligand derived from phen-DC3 108 a high-affinity quadruplex-binding substrate 109 that has some structural similarities to qtpyactually disrupts quadruplex structures.…”

“…22 Over the following years, a large number of studies on Ru II complexes and their interaction with quadruplexes and other related structures have been reported. [23][24][25][26][27] More recently, related research into Ir III complexes has developed 28,29 and cyclometalated polypyridyl Ir III metallointercalating complexes have proven to be particularly attractive as their photoexcited states are potentially tunable. [30][31][32][33] Yet, while such systems have been investigated as therapeutics and cell probes, [34][35][36][37][38][39][40][41][42][43][44] their use is often restricted asdue to their lower cationic chargethey frequently display poor inherent water solubility and lower DNA binding affinities.…”

“…22 Over the following years, a large number of studies on Ru II complexes and their interaction with quadruplexes and other related structures have been reported. 23–27…”

Luminescent Ruthenium(II) Complexes Used for the Detection of 8-Oxoguanine in the Human Telomeric Sequence

“…During the past decades, many studies demonstrated the abilities of ruthenium­(II) complexes as “DNA light switch” or as DNA specific sites photoprobes in vitro or in cellulo . − In the present study, we aim at investigating the potential of Ru­(II) polyazaaromatic complexes as 8-oxoG photoprobes in telomeric DNA and in duplex DNA. Complexes [Ru­(bpy) 2 napp] 2+ 1 , [Ru­(phen) 2 cpip] 2+ 2 , and [Ru­(phen) 2 salphen] 2+ 3 (Figure ) that are present as a mixture of Λ and Δ isomers were chosen for their reported ability to discriminate DNA topologies (such as G4 DNA and DNA mismatches) due to their high luminescence sensitivity. − We report on a brief description of the synthesis and the photophysical properties of compounds 1–3 along with a more detailed study of their 8-oxoG photoprobing capacities.…”

Photo-induced telomeric DNA damage in human cancer cells

“…In this context, a number of compounds including porphyrins, naphthalene, perylene diimide derivatives and metal complexes that can photo-oxidize G-quadruplex structures have been reported. 19,[21][22][23][24][25][26] However, none of them was shown to induce G-driven telomeric DNA lesions in cellulo. Herein, we report on the design of new smart G4 ligands based on Ru(II) complexes and combining (i) high affinity towards multimeric G4 structures of the telomeric sequence and (ii) photoreactivity to induce oxidative DNA damage.…”