Mn(II)−Texaphyrin as a Catalyst for the Decomposition of Peroxynitrite

Shimanovich, Roman; Hannah, Sharon; Lynch, Vincent M.; Gerasimchuk, Nikolay; Mody, Tarak D.; Magda, Darren; Sessler, Jonathan L.; Groves, John T.

doi:10.1021/ja005856i

Cited by 61 publications

(59 citation statements)

References 18 publications

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“…The noncompetitive inhibition of thioredoxin reductase and ribonucleotide reductase, resulting in increased levels of ROS, may also play a role. Only modest peroxynitrite scavenging ability has been evaluated with an Mn analogue (289). The rate constant for Mn(II)=Mn(III) oxidation by ONOO À is estimated at 3Â10 4 M À1 s À1 , whereby · NO 2 is formed.…”

Section: B Texaphyrinsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

467

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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Section: B Texaphyrinsmentioning

confidence: 99%

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

467

689

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“…[52] By using the same oxidative insertion methods used to generate the what is seen in the case of ferric porphyrins, the Zn II complex 38 proved notable in that only three of the five texaphyrin nitrogen atoms were found to be coordinated in the solid state. This was the case whether a single nitrate anion or two methanol molecules (see Figure 12) were coordinated to the Zn II center as ancillary ligands.…”

Section: Texaphyrin Complexesmentioning

confidence: 99%

“…À . [52] For clarity, the nitrate counterion is not shown; in the top view, one coordinating methanol molecule is omitted. .…”

Section: Medical Applications Of Texaphyrinsmentioning

confidence: 99%

Synthetic Expanded Porphyrin Chemistry

2003

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Expanded porphyrins are synthetic analogues of the porphyrins, and differ from these and other naturally occurring tetrapyrrolic macrocycles by containing a larger central core with a minimum of 17 atoms, while retaining the extended conjugation features that are a hallmark of these quintessential biological pigments. The result of core expansion is to produce systems with novel spectral and electronic features, interesting and, often unprecedented, cation-coordination properties, and, in many cases, an ability to bind anions in certain protonation states. Also adding to the appeal of expanded porphyrins is their central role in addressing issues of aromaticity. In many cases, they also display structural features, such as decidedly nonplanar "figure-eight" motifs, that have no antecedents in the chemistry of porphyrins or related macrocyclic compounds. In this Review, the various synthetic approaches now being employed to produce expanded porphyrins as well as their various applications-related aspects are discussed.

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“…These catalysts thus dramatically increase the rate of ONOO Ϫ isomerization, preempting the formation of oxidizing radical species and generating the harmless nitrate anion. This mode of catalysis manifests itself by dramatic shifts in the resulting nitrite-to-nitrate ratio when compared with the proton-catalyzed decomposition (Stern et al, 1996;Salvemini et al, 1998b;Shimanovich et al, 2001).…”

mentioning

confidence: 99%

A Role for Nitric Oxide-Mediated Peroxynitrite Formation in a Model of Endotoxin-Induced Shock

Cuzzocrea¹,

Mazzon²,

Paola³

et al. 2006

J Pharmacol Exp Ther

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The aim of the present study was to assess the relative contributions of peroxynitrite formation following induction of nitric-oxide synthase (iNOS) in the pathophysiology of endotoxin-induced shock in the rat. To this end, we used a selective inhibitor of iNOS, N- (3-(aminomethyl)benzyl)acetamidine (1400W), and a peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron III chloride (FeTTPs). Intravenous (i.v.) administration of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg) elicited a timedependent fall in mean arterial pressure as well as liver, renal, and pancreatic tissue damage. 1400W (3-10 mg/kg i.v.) administered 30 min before LPS delayed the development of hypotension but did not improve survival. On the other hand, FeTTPs administered (10 -100 mg/kg i.v.) inhibited in a dose-dependent manner LPS-induced hypotension, tissue injury, and improved mortality rate. In separate experiments, rats were treated with LPS (4 mg/kg) or saline for control, and their aortas were isolated and placed in organ baths 2 h later. Tissues from LPS-treated rats had significant inhibition of contractile activity to phenylephrine as well as a significantly impaired relaxation response to acetylcholine. FeTPPs, when administered (100 mg/kg i.v.) 1 h before LPS, prevented the LPS-induced aortic contractile and endothelial dysfunction. These results demonstrate that nitric oxide-derived peroxynitrite formation plays an important role in this model of endotoxemia. Our results also suggest that use of an iNOS inhibitor in this setting has little beneficial effect in part because, in the presence of a failing eNOS system, some NO is needed to maintain adequate organ function.Severe hypotension, development of hyporeactivity to vasopressors, and ultimately, progressive multiple organ dysfunction characterize the pathogenesis of Gram-negative bacterial endotoxic shock (Siegel et al., 1967). The cause of the systemic vasodilation associated with shock, in particular, is still unclear, although overproduction of the potent vasodilator nitric oxide (NO) from the inducible form of nitric-oxide synthase (iNOS) has been implicated (Nathan, 1992;Thiemermann, 1994;Rixen et al., 1997). Even so, results from iNOS knockout mice have been controversial, with some studies reporting reduced endotoxin-related hypotension and others indicating no effects or even detrimental outcomes (Nicholson et al., 1999). Furthermore, the extensive evaluation of selective inhibitors for iNOS, such as aminoguanidine and N-iminoethyl-L-lysine in models of shock, have likewise been disappointing and controversial (Thiemermann et al., 1995;Parratt, 1997).In septic shock, inhibition of the activity of the constitutive endothelial cell isoform of nitric-oxide synthase (eNOS) precedes the induction of iNOS (Lu et al., 1996). Moreover, down-regulation of eNOS occurs at time points similar to those where iNOS induction is seen. Collectively, these results indicate that the beneficial effects of NO from eNOS are probably lost ...

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Mn(II)−Texaphyrin as a Catalyst for the Decomposition of Peroxynitrite

Cited by 61 publications

References 18 publications

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Synthetic Expanded Porphyrin Chemistry

A Role for Nitric Oxide-Mediated Peroxynitrite Formation in a Model of Endotoxin-Induced Shock

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