Platinum(II)‐Based Optical Probes for Imaging Quadruplex DNA Structures via Phosphorescence Lifetime Imaging Microscopy

Abstract

G‐quadruplex DNA is a non‐canonical structure that forms in guanine‐rich regions of the genome. There is increasing evidence showing that G‐quadruplexes have important biological functions, and therefore molecular tools to visualise these structures are important. Herein we report on a series of new cyclometallated platinum(II) complexes which, upon binding to G‐quadruplex DNA, display an increase in their phosphorescence, acting as switch‐on probes. More importantly, upon binding to G‐quadruplexes they display a selective and distinct lengthening of their emission lifetime. We show that this effect can be used to selectively visualise these structures in cells using Phosphorescence Lifetime Imaging Microscopy (PLIM).

Shining New Light on Biological Systems: Luminescent Transition Metal Complexes for Bioimaging and Biosensing Applications

“…A related platinum(II) complex ( 503) has been developed for imaging G-quadruplex DNA structures in cells. 940 Binding of the complex to DNA promotes its aggregation, resulting in a significant increase in its emission lifetime from 75 ns to ca. 0.75 μs (for duplex DNA) and 1.42−1.90 μs (for G-quadruplex DNA), with the magnitude of the increase depends on the DNA topology.…”

“…Upon cellular internalization, the complex is released from the cage and enriched in the nucleoli. A related platinum(II) complex ( 503 ) has been developed for imaging G-quadruplex DNA structures in cells . Binding of the complex to DNA promotes its aggregation, resulting in a significant increase in its emission lifetime from 75 ns to ca .…”

Molecular Rotors: Fluorescent Sensors for Microviscosity and Conformation of Biomolecules

“…Thiophene‐based rotors have also been explored as G4 sensors, [146] and other G4 lifetime‐based probes have been reported, [147] however, their sensitivity to viscosity has not been investigated. Further development of molecular rotor‐based FLIM and/or phosphorescence‐based PLIM [148] probes for cellular G4s is currently ongoing in our group.…”