Cover Feature: Towards the Development of Photo‐Reactive Ruthenium(II) Complexes Targeting Telomeric G‐Quadruplex DNA (Chem. Eur. J. 72/2018)

Abstract

G‐quadruplexes are secondary structures of DNA that are found in the telomeric sequences. These structures are known to a play critical role in the development of cancer. This work presents the development of photo‐reactive ruthenium(II) complexes than can selectively target telomeric G‐quadruplex DNA. Interestingly, some of these complexes are able to trigger oxidative damage under light irradiation leading to cell death of cancer cells. The artwork shows this photo‐damaging of telomeric G‐quadruplex DNA by a ruthenium(II) complex. More information can be found in the Full Paper by E. Defrancq, B. Elias et al. on page 19216.

Binding and Beyond: What Else Can G‐Quadruplex Ligands Do?

“…Indeed, the field has recently taken steps towards engineering G4 ligands that exert different kinds of control on G4 that could be exploited toward biological and therapeutic ends. Such approaches harness the selectivity of G4-binding chemotypes to trigger a further molecular event, such as modification of the G4 by alkylation [80] or oxidation, [81] or as the basis for the localized generation of singlet-oxygen by photosensitization. [82] Furthermore, a small number of responsive G4 ligands have also been described.…”

“…In effort to confer additional G4 selectivity to Ru-TAP complexes, the Elias group conjugated a known G4 binding chemotype, chlorophenylimizdazophenanthroline (CPIP), to the Ru-TAP center (52-55, Figure 23). [81] Several approaches to introduce the TAP functionality were pursued, including by modifying the CPIP ligand itself to include the pyrazine functionality (53), by employing TAP ancillary ligands (54), or by combination of both strategies (55). The control ligand (52), containing only phenanthroline ligands and no TAP functionality, did not promote oxidation, observed as an increase in ligand luminescence on DNA binding (indicating the excited state is not quenched by an oxidative process).…”