The component of "ruthenium red" responsible for inhibition of mitochondrial calcium ion transport. Spectra, electrochemistry, and aquation kinetics. Crystal structure of .mu.-O-[(HCO2)(NH3)4Ru]2Cl3

Emerson, Jeffrey; Clarke, Michael J.; Ying, Wen Long; Sanadi, D.R.

doi:10.1021/ja00078a019

Cited by 59 publications

(70 citation statements)

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“…A solution of 18 M Ru360 in distilled water exhibited maximum light absorbance at 360 nm, with no detectable absorbance at 533 nm indicating that the preparation is free from ruthenium red contamination (not shown). The x-ray crystallographic data were identical to Ru360 reported previously (34). Thus, the light absorbance, the chemical structure derived from crystallograpy, and the molecular weight data led to the conclusion that the compound is Ru360 reported by Ying et al (33) and Emerson et al (34).…”

Section: Resultssupporting

confidence: 73%

“…The inhibition of Ca 2ϩ uptake into mitochondria however was shown to be due to a contaminant in the commercial preparations of RR (32). Recently, an oxygen-bridged dimeric ruthenium amine complex, which absorbs light at 360 nm (named Ru360), has been reported to inhibit Ca 2ϩ -stimulated respiration in isolated liver mitochondria (33,34). This compound would be an extremely useful tool for elucidating the role or the contribution of Ca 2ϩ uptake into mitochondria in vivo in isolated hearts or in situ in isolated cardiomyocytes if it penetrates the cell membrane but does not affect other cellular Ca 2ϩ transport processes or cardiac cell contractility.…”

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confidence: 99%

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Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake into Mitochondria in Vitroand in Situ in Single Cardiac Myocytes

Matlib¹,

Zhou²,

Knight³

et al. 1998

Journal of Biological Chemistry

297

256

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Ruthenium red is a well known inhibitor of Ca2؉ uptake into mitochondria in vitro. However, its utility as an inhibitor of Ca 2؉ uptake into mitochondria in vivo or in situ in intact cells is limited because of its inhibitory effects on sarcoplasmic reticulum Ca 2؉ release channel and other cellular processes. We have synthesized a ruthenium derivative and found it to be an oxygen-bridged dinuclear ruthenium amine complex. It has the same chemical structure as Ru360 reported previously (Emerson, J., Clarke, M. J., Ying, W-L., and Sanadi, D. R. (1993) J. Am. Chem. Soc. 115, 11799 -11805). Ru360 has been shown to be a potent inhibitor of Ca 2؉ -stimulated respiration of liver mitochondria in vitro. However, the specificity of Ru360 on Ca 2؉ uptake into mitochondria in vitro or in intact cells has not been determined. The present study reports in detail the potency, the effectiveness, and the mechanism of inhibition of mitochondrial Ca 2؉ uptake by Ru360 and its specificity in vitro in isolated mitochondria and in situ in isolated cardiac myocytes. Ru360 was more potent (IC 50 ‫؍‬ 0.184 nM) than ruthenium red (IC 50

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Section: Resultssupporting

confidence: 73%

mentioning

confidence: 99%

Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake into Mitochondria in Vitroand in Situ in Single Cardiac Myocytes

Matlib¹,

Zhou²,

Knight³

et al. 1998

Journal of Biological Chemistry

297

256

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“…The p K a values for Ru360′ were found to be 2.98(05) and 4.75(09) (Table ). These values are lower than those previously reported (4.18 and 7.2) . Given the lack of experimental details in this previous report, we are unable to determine the source of the discrepancy between our values.…”

Section: Resultscontrasting

confidence: 93%

“…As the cyclic voltammograms in Figure show, the reductions of Ru360′ are irreversible. The irreversible nature of these redox events may be a consequence of rapid chemical decomposition of this compound rapidly after reduction . Supporting this conclusion, Ru360′ loses its ability to inhibit the MCU when incubated with biologically relevant reducing agents.…”

Section: Resultsmentioning

confidence: 67%

Redox Stability Controls the Cellular Uptake and Activity of Ruthenium‐Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)

et al. 2020

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The mitochondrial calcium uniporter (MCU) is the ion channel that mediates Ca2+ uptake in mitochondria. Inhibitors of the MCU are valuable as potential therapeutic agents and tools to study mitochondrial Ca2+. The best‐known inhibitor of the MCU is the ruthenium compound Ru360. Although this compound is effective in permeabilized cells, it does not work in intact biological systems. We have recently reported the synthesis and characterization of Ru265, a complex that selectively inhibits the MCU in intact cells. Here, the physical and biological properties of Ru265 and Ru360 are described in detail. Using atomic absorption spectroscopy and X‐ray fluorescence imaging, we show that Ru265 is transported by organic cation transporter 3 (OCT3) and taken up more effectively than Ru360. As an explanation for the poor cell uptake of Ru360, we show that Ru360 is deactivated by biological reductants. These data highlight how structural modifications in metal complexes can have profound effects on their biological activities.

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“…The dropwise addition of an ethanolic solution of the ligand ntb to a refluxing solution of RuCl 3 ·3H 2 O in ethanol [22] led to the almost quantitative formation of the The molecular structure of the cation of complex 1 is shown in Figure 1 with 50 % probability thermal ellipsoids. The coordination geometry around Ru III is distorted octahedral in which four sites are occupied by the tetradentate ligand ntb and the remaining cis positions by two chloride ions.…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Synthesis, Structure and Spectral, and Electrochemical Properties of New Mononuclear Ruthenium(III) Complexes of Tris[(benzimidazol‐2‐yl)methyl]amine: Role of Steric Hindrance in Tuning the Catalytic Oxidation Activity

2009

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The new mononuclear Ru III complexes [Ru(ntb)Cl 2 ]Cl (1), [Ru(ntb)Cl 2 ]ClO 4 (1a), and [Ru(mntb)Cl 2 ]Cl (2) (ntb = tris-(benzimidazol-2-ylmethyl)amine, mntb = tris(N-methylbenzimidazol-2-ylmethyl)amine) have been synthesized and characterized. The X-ray crystal structure of 1 reveals that the coordination geometry around the Ru III center is distorted octahedral in which four sites are occupied by the tetradentate ligand ntb and the remaining cis positions by two chloride ions. The stronger Ru-N bzim bonds elongate the Ru-Cl bonds thereby labilizing the coordinated chloride ions. In the electronic absorption spectra the Ru III complexes show two bands corresponding to π(bzim) Ǟ t 2g (Ru) and pπ(Cl -) Ǟ t 2g (Ru) ligand-to-metal charge transfer (LMCT) transitions along with intraligand transitions in the UV region. Complex

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The component of "ruthenium red" responsible for inhibition of mitochondrial calcium ion transport. Spectra, electrochemistry, and aquation kinetics. Crystal structure of .mu.-O-[(HCO2)(NH3)4Ru]2Cl3

Cited by 59 publications

References 0 publications

Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake into Mitochondria in Vitroand in Situ in Single Cardiac Myocytes

Oxygen-bridged Dinuclear Ruthenium Amine Complex Specifically Inhibits Ca2+ Uptake into Mitochondria in Vitroand in Situ in Single Cardiac Myocytes

Redox Stability Controls the Cellular Uptake and Activity of Ruthenium‐Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)

Synthesis, Structure and Spectral, and Electrochemical Properties of New Mononuclear Ruthenium(III) Complexes of Tris[(benzimidazol‐2‐yl)methyl]amine: Role of Steric Hindrance in Tuning the Catalytic Oxidation Activity

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