title: The [Ru(Hedta)NO](0.1-) system: structure, chemical reactivity and biological assays.
abstract: The [Ru(II)(Hedta)NO(+)] complex is a diamagnetic species crystallizing in a distorted octahedral geometry, with the Ru-N(O) length 1.756(4) A and the RuNO angle 172.3(4) degrees . The complex contains one protonated carboxylate (pK(a)=2.7+/-0.1). The [Ru(II)(Hedta)NO(+)] complex undergoes a nitrosyl-centered one-electron reduction (chemical or electrochemical), with E(NO+/NO)=-0.31 V vs SCE (I=0.2 M, pH 1), yielding [Ru(II)(Hedta)NO](-), which aquates slowly: k(-NO)=2.1+/-0.4x10(-3) s(-1) (pH 1.0, I=0.2 M, CF(3)COOH/NaCF(3)COO, 25 degrees C). At pHs>12, the predominant species, [Ru(II)(edta)NO](-), reacts according to [Ru(II)(edta)NO](-)+2OH(-)-->[Ru(II)(edta)NO(2)](3-), with K(eq)=1.0+/-0.4 x 10(3) M(-2) (I=1.0 M, NaCl; T=25.0+/-0.1 degrees C). The rate-law is first order in each of the reactants for most reaction conditions, with k(OH(-))=4.35+/-0.02 M(-1)s(-1) (25.0 degrees C), assignable mechanistically to the elementary step comprising the attack of one OH(-) on [Ru(II)(edta)NO](-), with subsequent fast deprotonation of the [Ru(II)(edta)NO(2)H](2-) intermediate. The activation parameters were DeltaH(#)=60+/-1 kJ/mol, DeltaS(#)=-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 x 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 [Ru(II)(edta)NO](-) was studied in aortic rings without endothelium, and was compared with sodium nitroprusside (SNP). The times of maximal effects of [Ru(II)(edta)NO](-) and SNP were 2 h and 12 min, respectively, suggesting that [Ru(II)(edta)NO](-) releases NO slowly to the medium in comparison with SNP.
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, CEP: 13560-970, São Carlos, SP, Brazil.
authors.forename: Patrícia Graça
authors.initials: PG
authors.lastname: Zanichelli
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Miotto
authors.forename: Heder F G
authors.initials: HF
authors.lastname: Estrela
authors.forename: Fernanda Rocha
authors.initials: FR
authors.lastname: Soares
authors.forename: Dora M
authors.initials: DM
authors.lastname: Grassi-Kassisse
authors.forename: Regina C
authors.initials: RC
authors.lastname: Spadari-Bratfisch
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castellano
authors.forename: Federico
authors.initials: F
authors.lastname: Roncaroli
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Parise
authors.forename: José A
authors.initials: JA
authors.lastname: Olabe
authors.forename: Alba Regina M S
authors.initials: AR
authors.lastname: de Brito
authors.forename: Douglas Wagner
authors.initials: DW
authors.lastname: Franco
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004563:Electrochemistry; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D009569:Nitric Oxide / Q000737:chemistry / Q000493:pharmacokinetics; D012428:Ruthenium / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D009569:Nitric Oxide; D012428:Ruthenium; D004492:Edetic Acid; C026060:N-(hydroxyethyl)ethylenediaminetriacetic acid