Ultrafast excited state dynamics and light-switching of [Ru(phen)2(dppz)]2+ in G-quadruplex DNA

Abstract

The triplet metal to ligand charge transfer (3MLCT) luminescence of ruthenium (II) polypyridyl complexes offers attractive imaging properties, specifically towards the development of sensitive and structure-specific DNA probes. However, rapidly-deactivating dark state formation may compete with 3MLCT luminescence depending on different DNA structures. In this work, by combining femtosecond and nanosecond pump-probe spectroscopy, the 3MLCT relaxation dynamics of [Ru(phen)2(dppz)]2+ (phen = 1,10-phenanthroline, dppz = dipyridophenazine) in two iconic G-quadruplexes has been scrutinized. The binding modes of stacking of dppz ligand on the terminal G-quartet fully and partially are clearly identified based on the biexponential decay dynamics of the 3MLCT luminescence at 620 nm. Interestingly, the inhibited dark state channel in ds-DNA is open in G-quadruplex, featuring an ultrafast picosecond depopulation process from 3MLCT to a dark state. The dark state formation rates are found to be sensitive to the content of water molecules in local G-quadruplex structures, indicating different patterns of bound water. The unique excited state dynamics of [Ru(phen)2(dppz)]2+ in G-quadruplex is deciphered, providing mechanistic basis for the rational design of photoactive ruthenium metal complexes in biological applications.

Selective, Disruptive Luminescent Ru(II) Polypyridyl Probes of G-Quadruplex

“…Furthermore, marked changes in lifetime and emission intensity with different topologies were observed. In contrast to other reported Ru­(II)-based G4 ligands and indeed to Phen-DC3 itself, we have shown using CD titrations that Ru-PDC3 disrupts a variety of G4 structures …”

“…In contrast to other reported Ru(II)-based G4 ligands and indeed to Phen-DC3 itself, we have shown using CD titrations that Ru-PDC3 disrupts a variety of G4 structures. 64 We also report preliminary studies of the uptake and distribution of Ru-PDC3 in live cells and discuss its prospects as a G4 imaging probe.…”

“…While a number of G4 targeting metal complexes have been shown in solution to exhibit quadruplex binding, their high affinity for duplex DNA is likely to lead to poor discrimination from G4s in vivo, so tuning the structures to improve selectivity is required. , …”

Ruthenium(II) Polypyridyl Complexes and Their Use as Probes and Photoreactive Agents for G-quadruplexes Labelling

“…Even more recently, the ultrafast excited state dynamics of [Ru(phen) 2 ( dppz )] 2+ was studied in order to investigate the influence of the microenvironment around the complex on the population of both the bright and dark states [ 198 ]. The ultrafast dark state formation and decay rates are the most sensitive to the amount of water near the complex.…”

Interference reduction isothermal nucleic acid amplification strategy for COVID-19 variant detection

“…Luminescent metal complexes, especially iridium(III) complexes, have been employed to detect a range of species due to their high photostability, large Stokes shift, selective luminescence enhancement in the presence of G-quadruplex DNA, and long-lived emission that allows discrimination from fluorescence noise in biological matrices by use of time-resolved techniques [20] , [21] , [22] , [23] , [24] . Our previous studies have demonstrated that iridium(III) complex-based interference reduction biosensing strategies, such as nicking endonuclease-mediated interference reduction rolling circle amplification (NEM-IR-RCA) and interference reduction nucleic acid amplification strategy (IR-NAAS), are suitable for the highly specific detection of target nucleic acid sequences, such as miRNAs and COVID-19 RNAs [18] , [25] .…”