Tuning the Cellular Uptake Properties of Luminescent Heterobimetallic Iridium(III)–Ruthenium(II) DNA Imaging Probes

Abstract

The synthesis of two new luminescent dinuclear Ir(III)-Ru(II) complexes containing tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz) as the bridging ligand is reported. Unlike many other complexes incorporating cyclometalated Ir(III) moieties, these complexes display good water solubility, allowing the first cell-based study on Ir(III)-Ru(II) bioprobes to be carried out. Photophysical studies indicate that emission from each complex is from a Ru(II) excited state and both complexes display significant in vitro DNA-binding affinities. Cellular studies show that each complex is rapidly internalised by HeLa cells, in which they function as luminescent nuclear DNA-imaging agents for confocal microscopy. Furthermore, the uptake and nuclear targeting properties of the complex incorporating cyclometalating 2-(4-fluorophenyl)pyridine ligands around its Ir(III) centre is enhanced in comparison to the non-fluorinated analogue, indicating that fluorination may provide a route to promote cell uptake of transition-metal bioprobes.

A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition

“…Notably, the increase in relative viscosity of DNA on addition of 1 was significantly greater than that for either 2 or ethidium bromide (EB), indicating 1 induces structural distortion to DNA at a substantially greater level than mono-intercalation, and is therefore consistent with a multi-intercalative binding interaction33. In addition to these cell-free DNA binding studies, the phosphorescent metal to ligand charge-transfer (MLCT) excitation/emission wavelengths may provide a direct indication of cellular DNA binding and several RPCs function as DNA imaging probes1314. Accordingly, the ability of 1 and 2 to visualise DNA in fixed and membrane-permeabilised cells was characterised employing CLSM (confocal laser scanning microscopy).…”

“…As RPCs possess octahedral molecular geometries unobtainable to traditional carbon-based pharmacophores, unique biomolecular binding interactions may be achieved11. Furthermore, as many complexes are phosphorescent12, they possess a dual imaging capacity that allows verification of intracellular DNA targeting1314. While the majority of ruthenium-based anticancer compounds owe their effects to their reactivity and formation of coordinate (irreversible) bonds with DNA in a similar manner to cisplatin15, there has been growing interest in the bioactivity of RPCs that bind DNA solely by intercalation9.…”

Facile Synthesis of Luminescent Ir–Pt–Ir Trimetallic Complexes

“…They are synthetically versatile, allowing facile tuning of the emission color via modification of the cyclometalating (C^N) and/or ancillary ligand structure . Several examples of polynuclear cyclometalated iridium complexes have been reported recently, as well as some supramolecular structures where cyclometalated iridium is combined with another photoactive metal complex . Relevant to the present manuscript, there are a few multimetallic compounds involving cyclometalated iridium partnered with Pt II bis‐acetylide complexes, the latter being another well‐known class of phosphorescent organometallic complexes …”

Osmium(ii) polypyridyl polyarginine conjugate as a probe for live cell imaging; a comparison of uptake, localization and cytotoxicity with its ruthenium(ii) analogue

“…1,2 Their advantages are myriad, including tuneable emission, photostability and stokes shifted emissions. [8][9][10][11][12][13][14][15][16] Thus far, most of the focus has been on ruthenium, rhodium and iridium polypyridyl complexes. [8][9][10][11][12][13][14][15][16] Thus far, most of the focus has been on ruthenium, rhodium and iridium polypyridyl complexes.…”