Abstract
Due to their optical and electrochemical properties, ruthenium(II) polypyridyl complexes have been used in a wide array of applications. Since the discovery of the light-switch ON effect of [Ru(bpy)2dppz]2+ when interacting with DNA, the design of new Ru(II) complexes as light-up probes for specific regions of DNA has been intensively explored. Amongst them, G-quadruplexes (G4s) are of particular interest. These structures formed by guanine-rich parts of DNA and RNA may be associated with a wide range of biological events. However, locating them and understanding their implications in biological pathways has proven challenging. Elegant approaches to tackle this challenge relies on the use of photoprobes capable of marking, reversibly or irreversibly, these G4s. Indeed, Ru(II) complexes containing ancillary π-deficient TAP ligands can create a covalently linked adduct with G4s after a photoinduced electron transfer from a guanine residue to the excited complex. Through careful design of the ligands, high selectivity of interaction with G4 structures can be achieved. This allows the creation of specific Ru(II) light-up probes and photoreactive agents for G4 labelling, which is at the core of this review composed of an introduction dedicated to a brief description of G-quadruplex structures and two main sections. The first one will provide a general picture of ligands and metal complexes interacting with G4s. The second one will focus on an exhaustive and comprehensive overview of the interactions and (photo)reactions of Ru(II) complexes with G4s.
Highlights
When one thinks of DNA, one often thinks of the classical double-helix structure, B-DNA, that was discovered from X-ray data by Watson and Crick in 1953 [1]
Ruthenium(II) polypyridyl complexes have been widely studied for the last thirty years for their interaction with DNA. Investigating these complexes to interact with G-quadruplex structures has only started to gain interest in the last fifteen years. These G-quadruplex structures have yet to be fully understood but seem to play an important role as gene expression regulators as well as key targets for potential cancer treatment since they were found in telomeres
Ruthenium(II) polypyridyl complexes can play a significant role due to their remarkable behavior when interacting with G-quadruplexes
Summary
When one thinks of DNA, one often thinks of the classical double-helix structure, B-DNA, that was discovered from X-ray data by Watson and Crick in 1953 [1]. Their presence in the cell environment has been demonstrated at several sites and intensively studied at the telomeric ends of eukaryotic chromosomes [12,13] At these telomeric ends, DNA is organized as a guanine-rich single strand rather than a double helix, which allows a favored quadruplex conformation and a privileged interaction with small molecules [14,15,16]. Intensive research has been carried out over the past few decades to study G-quadruplexes as they have high potential to be used notably as therapeutic targets for cancer treatments thanks to their presence at the end of chromosomes [20] They are crucial in cells as they play the role, among others, of cellular clock by shortening with each cell division, which brings cells to a state of senescence. Polypyridyl complexes studied in presence of G-quadruplex structures will present their ability to interact and act as selective probes or potential anti-cancer agent which is the main focus of this review
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