Ruthenium(III) Polyaminocarboxylate Complexes: Efficient and Effective Nitric Oxide Scavengers

The preparation of two RuIII 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) Å3, and Z = 4. AMD6263 (C10H14N3O10Ru)
crystallized in the P21/c space group with a = 9.9043(4) Å, b = 13.1144(3) Å, c = 12.0914(4) Å, β = 100.191°,
V = 1545.8(5) Å3, and Z = 4. AMD3689 (C14H24.56N4O13.28Ru) crystallized in the P1̄ 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) Å3,
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.