Ruthenium(III) polyaminocarboxylate complexes: Efficient and effective nitric oxide scavengers

The preparation of two Ru-III polyaminocarboxylate complexes, AMD6245 and AMD6221, and their nitrosyl analogues, AMD6204, AMD6263, and AMD3689, is described. The compounds are characterized by IR, ES-MS, and C-13 and N-15 NMR spectroscopy where appropriate and cyclic voltammetry. The crystal structures for AMD6245, AMD6263, and AMD3689 are presented. AMD6245 (C10H14N2O9Ru) crystallized in the P2(1)/c space group with a = 8.4382(2) Angstrom, b = 8.8304(2) Angstrom, c = 17.6321(4) Angstrom, beta = 99.603', V = 1295.3(2) Angstrom(3), and Z = 4. AMD6263 (C10H14N3O10Ru) crystallized in the P2(1)/c space group with a = 9.9043(4) Angstrom, b = 13.1144(3) Angstrom, c 12.0914(4) Angstrom, beta = 100.191degrees, V = 1545.8(5) Angstrom(3), and Z = 4. AMD3689 (C14H24.56N4O13.28Ru) crystallized in the P (1) over bar space group with a = 8.838-(2) Angstrom, b = 9.452(3) Angstrom, c = 13.419(4) Angstrom, alpha = 78.413(6)0, beta = 75.804(6)degrees, gamma = 73.562(6)degrees, V = 1031.8(5) Angstrom(3), and Z = 2. The reaction of AMD6245 and AMD6221 with nitric oxide is investigated using EPR spectroscopy and stopped flow kinetics. Upon reaction with NO, a linear, diamagnetic {RuNO}(6) complex is formed. The substitution reaction of AMD6245 with NO proceeds with a second-order rate constant of 2.24 x 10(7) M-1 s(-1) at 7.3degreesC (pH = 7.4; 50 mM phosphate buffer). The substitution reaction of AMD6221 with NO proceeds with a second-order rate constant of 3 x 10(5) M-1 s(-1) at 20degreesC (pH = 7.4; 50 mM phosphate buffered saline). The NO scavenging ability was assessed using a RAW264 murine macrophage assay by measuring the difference in nitrite produced between untreated control cells and treated cells. At 100 muM AMD6245 has [NO2-] = 12.5 muM less than the untreated cells and AMD6221 has [NO2-] = 37.6 muM less than the untreated cells. There is an insignificant difference in the amount of nitrite produced between AMD6263 or AMD3689 treated cells and untreated cells.