Homo‐ and Heteroleptic Phototoxic Dinuclear Metallo‐Intercalators Based on Ru^II(dppn) Intercalating Moieties: Synthesis, Optical, and Biological Studies

Abstract

Article:Saeed, H., Jarman, P., Archer, S. et al. This is the peer reviewed version of the following article: Saeed, H., Jarman, P., Archer, S., Sreedharan, S., Saeed, I., Mckenzie, L., Weinstein, J., Buurma, N., Smythe, C. and Thomas, J. A. (2017), Homo-and heteroleptic phototoxic dinuclear metallo-intercalators based on RuII(dppn) intercalating moieties: synthesis, optical and biological studies.

Super‐Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

“…Currently, imaging subcellular structures relies upon fluorescent proteins, organic dyes, and quantum dots; however, none of those dyes are suitable for tracking the dynamics of subcellular structures due to their poor photostability and vulnerability to photobleaching . Studies have shown that using luminescent transition metal complexes (LTMCs), including Ru, Re, Pt, Au, and Zn, is an excellent alternative strategy that can overcome those drawbacks. For example, to image mitochondria, Tang et al reported a Zn(II) complex dye whose fluorescence intensity decayed to 10% after a short period of continuous scan under STORM .…”

From Chemotherapy to Phototherapy – Changing the Therapeutic Action of a Metallo‐Intercalating RuII‐ReI Luminescent System by Switching its Sub‐Cellular Location

“…Since the first report of its DNA intercalating properties, [1] the DNA “light‐switch” complex, [Ru(bpy) 2 (dppz)] 2+ , has been the subject of a huge variety of studies [2–6] and although it is not cell‐permeant itself, [7] derivatives that are internalized have been developed for a range of applications, [8–10] including as sensitizers for photodynamic therapy [11–13] . Analogous systems containing d 6 metal ions other than Ru II have also been reported, and these complexes can have photophysical and biological properties that are very different to their parent [14–17] .…”

“…With the aim of providing a facile route to more structurally complex oligonuclear architectures, the Thomas group has used achiral mononuclear complexes as building blocks in the “modular” synthesis of non‐threading dinuclear metallo‐intercalators [22] . Using this approach metal ions, linkers, and intercalating ligand can all be individually selected, allowing us to explore the properties of dinuclear Ru II systems with two different intercalating ligands [13] or heterodinuclear Ru II ‐Re I metallo‐intercalators [23,24] . We have also found the bridging ligand used to tether the intercalating moieties together can influence the photophysical and biophysical properties of these complexes [24,25] …”

“…Nevertheless, the complex behaves as a theranostic as it is both conventionally cytotoxic with a potency comparable to cisplatin and a STED nanoscopy probe that selectively localizes in the lysosomes and nuclei of live cells [24] . As we have previously discovered the nature of the intercalating ligand can change both the excited state and biological properties of related homometallic Ru II systems, [13,26–28] we set out to synthesize and study 2 3+ , Figure 1, a heterometallic complex containing two different intercalating ligands, these studies revealed that cytotoxicity, phototoxicity, and live‐cell localization are all profoundly altered by this single change.…”

Super-Resolution Tracking of Mitochondrial Dynamics with An Iridium(III) Luminophore

“…Currently, imaging subcellular structures relies upon fluorescent proteins 18, 19 , organic dyes 20 , and quantum dots 21 ; however, none of those dyes are suitable for tracking the dynamics of subcellular structures due to their poor photostability and vulnerability to photobleaching 22 . Studies have shown that using luminescent transition metal complexes (LTMCs) 23,24,25,26 , including Ru, Re, Pt, Au, and Zn, is an excellent alternative strategy that can overcome those drawbacks. For example, to image mitochondria, Tang et al reported a first-row Zn complex dye whose fluorescence intensity decayed to 10% after a short period of continuous scan under STORM 27 .…”