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 ¹³C and ¹⁵N NMR spectroscopy where appropriate and cyclic voltammetry. The crystal structures for AMD6245, AMD6263, and AMD3689 are presented. AMD6245 (C₁₀H₁₄N₂O₉Ru) crystallized in the P2₁/c space group with a = 8.4382(2) Å, b = 8.8304(2) Å, c = 17.6321(4) Å, β = 99.603°, V = 1295.3(2) ų, and Z = 4. AMD6263 (C₁₀H₁₄N₃O₁₀Ru) crystallized in the P2₁/c space group with a = 9.9043(4) Å, β = 13.1144(3) Å, c = 12.0914(4) Å, β = 100.191° V = 1545.8(5) Å, and Z = 4. AMD3689 (C₁₄H_24.56N₄O_13.28Ru) crystallized in the P1 space group with a = 8.838- (2) Å, b = 9.452(3) Å, c = 13.419(4) Å, α = 78.413(6)°, β = 75.804(6), γ = 73.562(6)°, V = 1031.8(5) ų, 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 × 10⁷ M^-1 s^-1 at 7.3 °C (pH = 7.4; 50 mM phosphate buffer). The substitution reaction of AMD6221 with NO proceeds with a second-order rate constant of 3 × 10⁵ M^-1 s^-1 at 20 °C (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 μM AMD6245 has [NO₂^-] = 12.5 μM less than the untreated cells and AMD6221 has [NO₂^-] = 37.6 μM 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.