Platinum-based phosphorescent lifetime probes for the visualisation of G-quadruplex DNA in cells

Abstract

DNA can fold into a range of different structures besides the canonical double helix. These structures have been shown to play important biological regulatory roles, highlighting that is not only DNA's sequence but also its structure that dictates its functions. However, detecting and visualising these structures in cells is challenging, due to their dynamic nature and low abundance at any one time, as compared to duplex DNA. In this paper we report the syntheses of three new platinum(II) complexes, coordinated to C^N^N^C and N^C^C^N ligands, and study their photophysical properties in the absence and presence of duplex and quadruplex DNA structures. We find that two of the probes switch on their phosphorescence intensity upon interaction with DNA. Moreover, we demonstrate that the phosphorescence lifetime of one of the probes shows distinct changes upon interaction with quadruplex DNA, as compared to duplex DNA or free in solution. Reassuringly, this probe shows no self-aggregation in the nuclei and nucleoli of live and fixed cells, allowing artefact-free imaging. Thus, we utilise Phosphorescence Lifetime Imaging Microscopy (PLIM) to visualise G-quadruplexes in live and fixed cells using this novel PLIM probe.