Cell studies of the DNA bis-intercalator Delta-Delta [micro-C4(cpdppz)2-(phen)4Ru2]4+: toxic effects and properties as a light emitting DNA probe in V79 Chinese hamster cells

Abstract

Coordination complexes of type [Ru(L)(3)](2+), where L is a nitrogen-containing aromatic bidentate ligand, can often be photolytically reduced, making them useful in studies of DNA- or protein-mediated electron transfer and in artifical photosynthesis model systems. Upon binding to DNA some Ru(L) complexes have been found to display strongly increased fluorescence compared with when free in solution, making those compounds interesting to test as DNA probes. Thus, they are becoming widely used in the chemistry community. Here, asynchronous cultures of V79 Chinese hamster cells were exposed to the DNA bis-intercalator Delta-Delta [mu-C4(cpdppz)(2)-(phen)(4)Ru(2)](4+) at 10(-10)-10(-4) M. The extraordinarily strong binding of the compound to DNA was the reason for testing its possible interference with DNA metabolism in intact mammalian cells. Exposure for 1 h to 10(-10)-10(-4) M did not significantly decrease DNA synthesis. Cells exposed to 10(-5) M for 27 h showed no staining of the nucleus, while DNA was stained in cells electroporated in the presence of the compound. However, the Ru dimer was probably taken up by pinocytosis, because numerous minute precipitates could be observed in the cytoplasm. Treatment for 24 h at concentrations of 10(-10)-10(-5) M did not inhibit growth, as indicated by cell density and mitotic activity. Neither did it affect chromosomal arrangements during mitosis. However, at 10(-4) M the density of cultures was reduced by approximately 45% and apoptotic cells were frequent, as opposed to mitoses. We also investigated the properties of the Ru dimer as a fluorescent DNA stain. The compound appears attractive as a red DNA stain when broad excitation in the visible range is desirable and extremely low background staining is essential. The low toxicity of the compound is a favourable trait in this context.

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…109 Önfelt et al reported that the binuclear Ru(II) complex, Δ - Δ [μ-C4(cpdppz) 2 -(phen) 4 Ru 2 ] 4+ (C4(cpdppz) 2 = N,N ’ bis-(cpdppz)-1,4-diaminobut-ane; cpdppz = 12-cyano12,13-carbonyl-11 H -cyclopenta[ b ]- dipyrido[3,2- h :2′3’- j ]phen-azine-12-carbonyl; phen = 1,10-phenanthroline), binds with high affinity to DNA (K b ∼10 8 M −1 ). 110 The entry of this complex into the nucleus was facilitated by electroporation, and it induced the run apoptosis at 10 −4 M. Thomas et al . showed that the dinuclear compound 2b (Fig.…”

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

“…[26][27][28] However, similar to their Ir III analogues, there are only a few examples of Ru II complexes able to visualise nuclear DNA in live cells. [29][30][31] Clearly then, promoting cellular uptake of such complexes whilst retaining nuclear targeting remains a significant challenge in this research. However, despite this huge volume of research into either Ir III or Ru II complexes, reports on iridium(III)-ruthenium(II) conjugate complexes are surprisingly uncommon.…”

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

“…Despite the attractive photophysical properties and promising DNA-binding characteristics of binuclear ruthenium complexes, there have been relatively few studies focusing on the interaction between these complexes and live cells [3, 4, 20, 21]. As a consequence, knowledge regarding cellular uptake, intracellular localization, biomolecular binding, and the influence of enantiomeric differences for these events is limited.…”