In vivo effects of the controlled NO donor/scavenger ruthenium cyclam complexes on blood pressure

Marcondes, F. G.; Ferro, Ana Paula; Torsoni, Marcio Alberto; Sumitani, Marie; Clarke, Michael J.; Franco, Douglas Wagner; Tfouni, Elia; Krieger, Marta Helena

doi:10.1016/s0024-3205(02)01528-x

Cited by 68 publications

(87 citation statements)

References 46 publications

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“…Among the NO donors, ruthenium nitrosyl complexes are particularly attractive because they are stable, can be either water soluble or not, deliver NO at different rates upon activation by reduction at biologically accessible potentials and/or by light irradiation, in either solution or matrices. [14][15][16][17][18]34,[40][41][42][43][44][45][46][47][48][49] These properties can be tuned by the adequate choice of ligands. 14,18 It should be pointed out that interesting biological activities for several of these complexes have already been reported.…”

Section: Introductionmentioning

confidence: 99%

“…14,18 It should be pointed out that interesting biological activities for several of these complexes have already been reported. 14,17,21,33,34,[37][38][39] Because NO can be either beneficial or harmful depending on its bioavailability, compounds capable of releasing NO in a specific biological target have potential biological applications and could be useful tools to study the physiological action of NO. Efforts from this laboratory have been directed toward this goal, using several strategies.…”

Section: Introductionmentioning

confidence: 99%

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Chemical and photochemical properties of a ruthenium nitrosyl complex with the N-monosubstituted cyclam 1-(3-Propylammonium)-1,4,8,11-tetraazacyclotetradecane

Ferreira¹,

Tfouni²

2010

J. Braz. Chem. Soc.

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O complexo aminofuncionalizado trans-[Ru(NO)Cl(1-pramcyH)](PF 6 ) 3 (1-pramcyH = 1-(3-propilamônio)-1,4,8,11-tetraazaciclotetradecano) foi sintetizado através da reação do trans-[RuCl(tfms)(1-pramcyH)](tfms) 2 (tfms = trifluorometanossulfonato) com óxido nítrico (NO) em solução aquosa ácida. O complexo foi caracterizado por análise elementar, espectroscópica (UVvis, IV, RMN de 1 H e 13 C) e eletroquímica. Dois valores de pK a (7,0 e 8,2) foram determinados para trans- [Ru(NO) ](PF 6 ) 3 e foram atribuídos a um dos prótons do grupo amina do cyclam e ao propilamônio. A redução do trans- [Ru(NO) ] 3+ leva à saída rápida de cloreto seguida de saída lenta de NO, enquanto a irradiação do complexo em solução aquosa desaerada resulta na labilização fotoquímica do NO. O rendimento quântico para a fotoaquação do NO diminui com o aumento do comprimento de onda de irradiação e com a diminuição do pH, e é observável apenas a l irr < 370 nm. O comportamento do trans- [Ru(NO) ] 3+ é semelhante ao do complexo análogo trans- [Ru(NO) Cl(cyclam)] 2+ , porém difere daquele do complexo com carboxipropil como substituinte.The amine-functionalized trans- [Ru(NO) ](PF 6 ) 3 complex (1-pramcyH = 1-(3-propylammonium)-1,4,8,11-tetraazacyclotetradecane) was synthesized from trans- [RuCl(tfms) (1-pramcyH)](tfms) 2 (tfms = trifluoromethanesulfonate) in acidic aqueous solution in the presence of nitric oxide (NO). The complex was characterized by elemental, spectroscopic (UV-Vis, IR, 1 H and 13 C NMR) and electrochemical analyses. Two pK a values (7.0 and 8.2) were estimated for trans- [Ru(NO) ](PF 6 ) 3 and were assigned to one of the cyclam nitrogen protons and to the protonated aminopropyl group. Reduction of trans- [Ru(NO) ] 3+ results in rapid loss of chloride followed by slower loss of NO, while irradiation of the complex in aqueous deaerated conditions suggests photochemical labilization of NO. The quantum yields for NO photoaquation decrease as the irradiation wavelength increases, being noticeable only at l irr < 370 nm, and increase as pH increases. The behavior of trans- [Ru(NO) ] 3+ , which contains an aminopropyl substituted cyclam, parallels that reported for the analogous complex with the unsubstituted ligand, but differs from that described for the complex in which carboxypropyl is the substituent. Keywords: nitrosyl, ruthenium, nitric oxide donor, substituted cylam, mono-N-functionalized cyclam IntroductionThe discovery of the participation of nitric oxide (NO) in a wide range of physiological processes and pathologies 1 has launched investigations on NO donors, including metal nitrosyl complexes in solution or immobilized in matrices, aiming at the understanding of both fundamental aspects and biological activity for potential applications. Among the NO donors, ruthenium nitrosyl complexes are particularly attractive because they are stable, can be either water soluble or not, deliver NO at different rates upon activation by reduction at biologically accessible Chemical and Photochemical Properties of a Ruthenium Nitrosyl...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemical and photochemical properties of a ruthenium nitrosyl complex with the N-monosubstituted cyclam 1-(3-Propylammonium)-1,4,8,11-tetraazacyclotetradecane

Ferreira¹,

Tfouni²

2010

J. Braz. Chem. Soc.

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“…However, the growing interest in NO physiology since the mid 1980's has led to the development of a variety of new NO donors that offer several advantages over conventional NO donors (1,5). Recently, several new metal complexes have been studied as NO donors or scavengers, including nitrosyl ruthenium complexes, nitrite complexes and related species (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

New nitric oxide donors based on ruthenium complexes

Lunardi

Silva

Bendhack

2009

Braz J Med Biol Res

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Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K + channels as well as induce vasodilatation by a decrease in cytosolic Ca 2+ . Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O 2 -) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O 2 -may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

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“…Fundamentados nisto, alguns pesquisadores estudaram a ação biológica de vários tipos de complexos nitrosilo de rutênio aquo-solúveis, (WIERASZKO et al, 2001;SMITH & DASGUPTA, 2001;MARCONDES et al, 2002;BONAVENTURA et al, 2004;ZANICHELLI et al, 2004;TFOUNI et al, 2005;KARIDI et al, 2005).…”

Section: Complexos Metálicos Na Medicinaunclassified

Reatividade química e fotoquímica de complexos nitrosilos de rutênio do tipo [Ru(terpy)(L)NO]n+

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In vivo effects of the controlled NO donor/scavenger ruthenium cyclam complexes on blood pressure

Cited by 68 publications

References 46 publications

Chemical and photochemical properties of a ruthenium nitrosyl complex with the N-monosubstituted cyclam 1-(3-Propylammonium)-1,4,8,11-tetraazacyclotetradecane

Chemical and photochemical properties of a ruthenium nitrosyl complex with the N-monosubstituted cyclam 1-(3-Propylammonium)-1,4,8,11-tetraazacyclotetradecane

New nitric oxide donors based on ruthenium complexes

Reatividade química e fotoquímica de complexos nitrosilos de rutênio do tipo [Ru(terpy)(L)NO]n+

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