- Redox Stability Controls the Cellular Uptake and Activity of Ruthenium-Based Inhibitors of the Mitochondrial Calcium Uniporter (MCU)
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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.
- Harris, Hugh H.,Lai, Barry,Lovett, James,Wilson, Justin J.,Woods, Joshua J.
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supporting information
p. 6482 - 6491
(2020/03/05)
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- Syntheses of cis- and trans-tetraamminedichlororuthenium(III) chloride
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The syntheses of the salts cis-and trans-tetraamminedichlororuthenium(III) chloride are reported. The two isomers are precursors to a number of di-substituted ruthenium(II) and (III) complexes.
- Boggs, Susan E.,Clarke, Richard E.,Ford, Peter C.
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p. 129 - 130
(2008/10/08)
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- A new procedure to synthesize cis-[Ru(NH3)4L2](n+) species containing ruthenium(II) or ruthenium(III) using tetraamino (3,4-diolatobenzoato)ruthenium(II) as precursor
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The preparation of [Ru(NH3)4(diox-COO)], where diox-COO is 3,4-diolatobenzoate, was achieved using pentamminechlororuthenium(III) chloride and 3,4-dihydroxybenzoic acid in basic medium. The neutral quinone complex is extremely soluble in water and easily purified by ion-exchange chromatography. The chemical or electrochemical reduction, in acidic medium, produces cis-[Ru(NH3)4(H2O)2](2+), indicating this dioxolene ruthenium complex to be useful precursor to prepare cis-tetraammineruthenium(II) or ruthenium(III) species.
- Silva, Roberto Santana da,Tfouni, Elia,Lever, A. B. P.
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p. 427 - 430
(2008/10/08)
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- Electronic coupling in mixed-valence binuclear ruthenium ammine complexes as probed by an electrochemical method and an extension of Mulliken's theory of donor-acceptor interactions
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An electrochemical approach to assessing the degree of electronic coupling in mixed-valence binuclear complexes is outlined. The method relies on the comparison of electrochemical potential shifts induced at both the directly and indirectly perturbed metal sites when a ligand substitution process is carried out at one site, e.g., [symmetric] (NH3)5Ru-Lbr-Ru(NH3) 54+/5+/6+ → [asymmetric] L(NH3)5Ru-Lbr-Ru(NH3) 54+/5+/6+, where the bridging ligand Lbr is either pyrazine or 4-cyanopyridine and the perturbing ligand L is a substituted pyridine. It is found that the degree of electronic coupling in these systems is at least three times that which would be predicted based solely on spectroscopic measurements. The stabilization energy due to electron delocalization in these complexes can be accounted for with near-quantitative accuracy. It is also shown how the Mulliken analysis of the data allows for an estimation of the Wolfsberg-Helmholz constant K, which can be used in the calculation of off-diagonal matrix elements for molecular donor-acceptor interactions.
- Salaymeh, Faleh,Berhane, Samson,Yusof, Rohana,De La Rosa, Roger,Fung, Ella Y.,Matamoros, Regina,Lau, Kent W.,Zheng, Qian,Kober, Edward M.,Curtis, Jeff C.
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p. 3895 - 3908
(2008/10/08)
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- Reduction of oxygen by ruthenium(II) ammines
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The reduction of O2 to H2O2 by a series of ruthenium(II) ammines has been studied in aqueous acidic solution at 25.0 °0C and 0.1 M ionic strength in noncomplexing media. The rate law is -d[Ru(II)]/dt = 2k1[Ru(II)][O2], with k1 = 1.08 × 10-1, 1.38 × 10-1, 3.03 × 10-2, and 7.73 × 10-3 M-1 s-1 for [Ru(NH3)5isn]2+ (isn = isonicotinamide), cis-[Ru(NH3)4isn(H2O)]2+, trans-[Ru(NH3)4isn(H2O)2+, and [Ru(NH3)4phen]2+, respectively. The reaction of [Ru(NH3)5isn]2+ is inhibited by [Ru(NH3)5isn]3+, and the inhibition increases with decreasing acidity. These results are accommodated by a mechanism involving outer-sphere formation of O2-; the Ru(III)/pH effect arises from a competition between the reaction of O2- with Ru(III) and the protonation of O2- followed by its reaction with Ru(II). The rate constants are correlated by a linear free-energy relation, (LFER), and they are consistent with the Marcus cross relation. Its application yields a self-exchange rate for the O2/O2- couple of about 1 × 103 M-1 s-1. In the presence of Cl-, the reaction of trans-[Ru(NH3)4isn(H2O)]2+ has two additional terms in the rate law: -d In [Ru(II)]/dt = 2(k1 + k5LCl[Cl-] + k6KCl[Cl-][H+])[O2], with k5 = 7.84 × 10-1 M-1 s-1, k6 = 1.40 × 102 M-2 s-1, and KCl = 0.39 M-1. The k5 path fits the LFER when it is treated as the autoxidation of trans-[Ru(NH3)4isnCl]+, and the k6 path probably involves direct formation of HO2 by the reaction of O2 with [Ru(NH3)4(isn)Cl]+.
- Stanbury, David M.,Haas, Otto,Taube, Henry
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p. 518 - 524
(2008/10/08)
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