The [Ru(Hedta)NO](0.1-) system: structure, chemical reactivity and biological assays.
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.
Zanichelli
Patrícia Graça
PG
Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São Carlense, CEP: 13560-970, São Carlos, SP, Brazil.
Miotto
Alexandre M
AM
Estrela
Heder F G
HF
Soares
Fernanda Rocha
FR
Grassi-Kassisse
Dora M
DM
Spadari-Bratfisch
Regina C
RC
Castellano
Eduardo E
EE
Roncaroli
Federico
F
Parise
Alejandro R
AR
Olabe
José A
JA
de Brito
Alba Regina M S
AR
Franco
Douglas Wagner
DW
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
D009569:Nitric Oxide; D012428:Ruthenium; D004492:Edetic Acid; C026060:N-(hydroxyethyl)ethylenediaminetriacetic acid