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

The cytological stain, ruthenium red, effectively inhibits mitochondrial Ca2+aq uptake; however, the majority of this activity has been attributed to an impurity. This component has now been isolated and a derivative, mu-O-[(HCO2)(NH3)4Ru]2Cl3, characterized by X-ray diffraction, spectroscopy, and electrochemistry. The compound crystallizes in the orthorhombic space group Pnn2 (No. 34), with unit cell constants of a = 8.588 (1), b = 13.335 (2), c = 7.602 (2) angstrom, Z = 2, and R = 0.024. The bridging Ru-O bond is quite short (1.8240(6) angstrom), while the Ru-O(formate) bond length (2.033(3) angstrom) is typical for a Ru-O single bond. The equatorial ammine-ruthenium bond lengths average 2.11(2) angstrom. The placement of the mu-O on a crystallographic two-fold axis dictates that the two metal centers are identical. The crystallographic equivalence together with electrochemical evidence (E-degrees = 1.17 and 0.05 V) indicates strong electronic coupling between the mixed-valent ruthenium centers. The apical formates are easily replaced by chlorides in HCl. Aquation rates of both the formato and chloro complexes are pH dependent. For the formato complex k(obs) is given by k(obs) = (k1[H+]2 + k2[H+]K(a1) + k3K(a1)K(a2))/([H+]2 + [H+]K(a) + K(a1)K(a2))), where k1 = (7.8 +/-0.1) x 10(-3) s-1, k2 = (1.2 +/- 0.1) x 10(-4) s-1, k3 = approximately 4 x 10(-4) s-1, pK(a1) = 2.45 +/- 0.07, and pK(a2) = approximately 9. The active species in solution appears to be the oxo-bridged ion, [X(NH3)4Ru-O-Ru(NH3)4X]3+, where X = Cl- or OH-. The hydroxo-capped complex decomposes above pH 7. Theoretical calculations show these ions to be highly deformable, which may partially explain their ability to inhibit Ca2+ binding to a number of different sites.