The [Ru(Hedta)NO]0,1− system: structure, chemical reactivity and biological assays

The [RuII(Hedta)NO+] complex is a diamagnetic species crystallizing in a distorted octahedral geometry, with the Ru–N(O) length 1.756(4) Å and the RuNO angle 172.3(4)°. The complex contains one protonated carboxylate (pKa=2.7±0.1). The [RuII(Hedta)NO+] complex undergoes a nitrosyl-centered one-electron reduction (chemical or electrochemical), with ENO+/NO=−0.31 V vs SCE (I=0.2 M, pH 1), yielding [RuII(Hedta)NO]−, which aquates slowly: k–NO=2.1±0.4×10−3 s−1 (pH 1.0, I=0.2 M, CF3COOH/NaCF3COO, 25 °C). At pHs>12, the predominant species, [RuII(edta)NO]−, reacts according to [RuII(edta)NO]−+2OH−⇒[RuII(edta)NO2]3−, with Keq=1.0±0.4×103 M−2 (I=1.0 M, NaCl; T=25.0±0.1 °C). The rate-law is first order in each of the reactants for most reaction conditions, with kOH−=4.35±0.02 M−1s−1 (25.0 °C), assignable mechanistically to the elementary step comprising the attack of one OH− on [RuII(edta)NO]−, with subsequent fast deprotonation of the [RuII(edta)NO2H]2− intermediate. The activation parameters were ΔH#=60±1 kJ/mol, ΔS#=−31±3 J/Kmol, consistent with a nucleophilic addition process between likely charged ions. In the toxicity up-and-down tests performed with Swiss mice, no death was observed in all the doses administered (3–9.08×10−5 mol/kg). The biodistribution tests performed with Wistar male rats showed metal in the liver, kidney, urine and plasma. Eight hours after the injection no metal was detected in the samples. The vasodilator effect of [RuII(edta)NO]− was studied in aortic rings without endothelium, and was compared with sodium nitroprusside (SNP). The times of maximal effects of [RuII(edta)NO]− and SNP were 2 h and 12 min, respectively, suggesting that [RuII(edta)NO]− releases NO slowly to the medium in comparison with SNP. [Copyright &y& Elsevier]