A ruthenium(II) polypyridyl complex for direct imaging of DNA structure in living cells

Abstract

In the search for new biological imaging agents, metal coordination compounds able to emit from triplet metal-to-ligand charge transfer (MLCT) states offer many advantages as luminescent probes of DNA structure. However, poor cellular uptake restricts their use in live cells. Here, we present a dinuclear ruthenium(II) polypyridyl system that works as a multifunctional biological imaging agent staining the DNA of eukaryotic and prokaryotic cells for both luminescence and transition electron microscopy. This MLCT 'light switch' complex directly images nuclear DNA of living cells without requiring prior membrane permeabilization. Furthermore, inhibition and transmission electron microscopy studies show this to be via a non-endocytotic, but temperature-dependent, mechanism of cellular uptake in MCF-7 cells, and confocal microscopy reveals multiple emission peaks that function as markers for cellular DNA structure.

Lipophilic ruthenium complexes with tuned cell membrane affinity and photoactivated uptake

“…Barton et al have recently shown the usefulness of this effect for studying the cellular uptake and nuclear localization of Ru(II) dppz complexes [3,4]. Similar complexes have also been used as probes for cell viability and nuclear staining [5,6]. We have previously shown that Ru(II) dppz complexes, made more hydrophobic by substitution with alkyl ether chains, are versatile as photophysical probes for phospholipid bilayers [7,8].…”

Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes as anticancer drug candidates

“…173 They previously reported the cellular uptake properties of the dinuclear Ru(II) complex 116 demonstrating that this luminescent light switch complex functions as a DNA imaging agent. 161 On the other hand, the most lipophilic analogue 115 was found to have possible applications as an in cellulo imaging agent targeting mainly lipid-dense endoplasmic reticulum (ER). 173 Cellular localisation studies showed that the targets of this compound are biological membranes with the major accumulation recorded in the ER.…”

Photo-induced cytotoxicity and anti-metastatic activity of ruthenium(ii)–polypyridyl complexes functionalized with tyrosine or tryptophan

“…Literature reports have demonstrated that more lipophilic cationic reagents generally accumulate preferentially in the cell membrane while analogous reagents with comparable overall charge but relatively lower lipophilicity preference the nucleus. 45,46 The dot-like structures with red fluorescence observed from the cytoplasm and cell membrane are reminiscent of another lipophilic Ru(II)-polypyridyl complexes which is observed in phospholipid bilayer of the cell membrane. 47 Figure 6.…”