Excess NO Research Articles

THE ROLE OF iNOS FOR HEPATIC GLUCOSE PRODUCTION IN MURINE SEPTIC SHOCK

Introduction: Sepsis leads to depressed endogenous glucose production rate, and in this context the role of inducible NO synthase (iNOS) has been controversially discussed. Therefore, we investigated the effects of genetic and pharmacologic iNOS deletion on hepatic glucose production during murine septic shock. Methods: 15 h after cecal ligation and puncture (CLP) iNOS-/- mice, wildtype mice (WT) treated with the selective iNOS-inhibitor GW274150 and WT controls were anesthetized, mechanically ventilated and instrumented. Intravenous colloids and noradrenaline (NA) were titrated to achieve normotensive, hyperdynamic hemodynamics. 24 h after CLP, hepatic glucose production was derived from liver tissue isotope concentrations measured after steady-state infusion of stable isotope-labelled 1,2,3,4,5,6-13C6-glucose. Date are median (range) tested with a rank sum analysis. Results: Both genetic and pharmacologic iNOS blockade resulted in significantly lower NA requirements to achieve target hemodynamics (P < 0.001 vs. WT controls). Hepatic glucose production was also significantly higher in these animals (4.3 (3.2-8.4) and 5.0 (3.7-6.3) vs. 1.9 (0.4-2.9) mg/g·h in WT mice, P < 0.001) despite reduced NA infusion rates. Conclusions: Our data suggest a crucial role for iNOS activation-affiliated excess NO release during murine septic shock-induced depression of de novo hepatic glucose production rate, most likely as a result of an NO-mediated defect in cellular energy metabolism.

TAP study of NOx storage and reduction on Pt/Al 2O 3 and Pt/Ba/Al 2O 3

A systematic mechanistic study of NO storage and reduction over Pt/Al 2O 3 and Pt/BaO/Al 2O 3 is carried out using Temporal Analysis of Products (TAP). NO pulse and NO/H 2 pump-probe experiments at 350 °C on pre-reduced, pre-oxidized, and pre-nitrated catalysts reveal the complex interplay between storage and reduction chemistries and the importance of the Pt/Ba coupling. NO pulsing experiments on both catalysts show that NO decomposes to major product N 2 on clean Pt but the rate declines as oxygen accumulates on the Pt. The storage of NO over Pt/BaO/Al 2O 3 is an order of magnitude higher than on Pt/Al 2O 3 showing participation of Ba in the storage even in the absence of gas phase O 2. Either oxygen spillover or transient NO oxidation to NO 2 is postulated as the first steps for NO storage on Pt/BaO/Al 2O 3. The storage on Pt/Ba/Al 2O 3 commences as soon as Pt–O species are formed. Post-storage H 2 reduction provides evidence that a fraction of NO is not stored in close proximity to Pt and is more difficult to reduce. A closely coupled Pt/Ba interfacial process is corroborated by NO/H 2 pump-probe experiments. NO conversion to N 2 by decomposition is sustained on clean Pt using excess H 2 pump-probe feeds. With excess NO pump-probe feeds NO is converted to N 2 and N 2O via the sequence of barium nitrate and NO decomposition. Pump-probe experiments with pre-oxidized or pre-nitrated catalyst show that N 2 production occurs by the decomposition of NO supplied in a NO pulse or from the decomposition of NOx stored on the Ba. The transient evolution of the two pathways depends on the extent of pre-nitration and the NO/H 2 feed ratio.

Intercomparison of ultraviolet photometry and gas‐phase titration techniques for ozone reference standards at ambient levels

Intercomparison experiments were made between two independent techniques for ozone (O3) reference standards often used as the primary standards in air quality monitoring networks. These techniques include ultraviolet absorption photometry of O3 at the 253.7‐nm Hg line and gas‐phase titration of O3 with excess NO. For ultraviolet photometry, a well‐designed and maintained standard reference photometer (SRP) built by the National Institute of Standards and Technology (USA) was employed. For gas‐phase titration (GPT), an existing system was significantly modified by the National Institute for Environmental Studies (Japan) by using gravimetric NO/N2 standard gases, accurate flow measurement systems based on laminar flow elements, and two chemiluminescence NO detectors to minimize uncertainty in the measurements, which had previously been a major shortcoming of this method. Uncertainty in the improved GPT system was reduced to less than 0.4% above 100 nmol mol−1 O3 mole fraction. A series of comparison runs between the two methods over the course of 13 months from August 2004 to August 2005 showed a significant discrepancy, which cannot be explained by the measurement uncertainties attributed to either SRP or GPT in the range of 80–800 nmol mol−1 O3, where GPT was about 2% higher than SRP. This result indicates possible biases in the currently existing O3 reference standards and warrants further studies to identify and characterize possible sources of the systematic discrepancy.

Anaphylactic shock depends on PI3K and eNOS-derived NO.

Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCalpha1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis.

Reactivity of NO/NO2–NH3 SCR system for diesel exhaust aftertreatment: Identification of the reaction network as a function of temperature and NO2 feed content

We present a systematic study of the NH3-SCR reactivity over a commercial V2O5–WO3/TiO2 catalyst in a wide range of temperatures and NO/NO2 feed ratios, which cover (and exceed) those of interest for industrial applications to the aftertreatment of exhaust gases from diesel vehicles. The experiments confirm that the best deNOx efficiency is achieved with a 1/1 NO/NO2 feed ratio. The main reactions prevailing at the different operating conditions have been identified, and an overall reaction scheme is herein proposed.Particular attention has been paid to the role of ammonium nitrate, which forms rapidly at low temperatures and with excess NO2, determining a lower N2 selectivity of the deNOx process. Data are presented which show that the chemistry of the NO/NO2–NH3 reacting system can be fully interpreted according to a mechanism which involves: (i) dimerization/disproportion of NO2 and reaction with NH3 and water to give ammonium nitrite and ammonium nitrate; (ii) reduction of ammonium nitrate by NO to ammonium nitrite; (iii) decomposition of ammonium nitrite to nitrogen. Such a scheme explains the peculiar deNOx reactivity at low temperature in the presence of NO2, the optimal stoichiometry (NO/NO2=1/1), and the observed selectivities to all the major N-containing products (N2, NH4NO3, HNO3, N2O). It also provides the basis for the development of a mechanistic kinetic model of the NO/NO2–NH3 SCR reacting system.

Contribution of dissolved organic nitrogen deposition to nitrogen saturation in a forested mountainous watershed in Tsukui, Central Japan

Nitrogen (N) budget was estimated with dissolved inorganic N (DIN) and dissolved organic N (DON) in a forested mountainous watershed in Tsukui, Kanagawa Prefecture, about 50 km west of Tokyo in Central Japan. The forest vegetation in the watershed was dominant by Konara oak (Quercus serrata) and Korean hornbeam (Carpinus tschonoskii), and Japanese cedar (Cryptomeria japonica). Nitrate (NO3−) concentration in the watershed streamwater was averagely high (98.0 ±± 19 (±± SD, n = 36) μmol L−1) during 2001–2003. There was no seasonal and annual changes in the stream NO−3 concentration even though the highest N uptake rate presumably occurred during the spring of plant growing season, a fact indicating that N availability was in excess of biotic demands. The DON deposition rates (DON input rates) in open area and forest area were estimated as one of the main N sources, accounting for about 32% of total dissolved N (TDN). It was estimated that a part of the DON input rate contributed to the excessive stream NO−3 output rate under the condition of the rapid mineralization and nitrification rates, which annual DON deposition rates were positively correlated with the stream NO3− output rates. The DON retention rate in the DON budget had a potential capacity, which contributed to the excessive stream NO−3 output rate without other N contributions (e.g. forest floor N or soil N).

Protective effects of burdock ( Arctium lappa Linne) on oxidation of low-density lipoprotein and oxidative stress in RAW 264.7 macrophages

The protective effects of burdock ( Arctium lappa Linne) on oxidation of low-density lipoprotein (LDL) and nitric oxide production were investigated. The results showed that methanolic extracts of burdock (MEB) and their major components, chlorogenic acid (CHA) and caffeic acid (CA), showed marked antioxidant activity against oxidative damage of liposome ( p < 0.05), deoxyribose ( p < 0.05) and protein ( p < 0.05). In addition, at a concentration of 500 μg/ml, the inhibitory effect of MEB on LDL oxidation was 66.9% compared to the control ( p < 0.05). MEB, at 200 μg/ml, not only enhanced GSH levels, but also increased activity of GSH reductase, GSH peroxidase, GSH transferase and catalase, which were 3.82-, 24.9-, 4.35- and 3.02-fold compared to the control ( p < 0.05), respectively. MEB directly scavenged nitric oxide in a concentration-dependent fashion ( p < 0.05). Moreover, MEB showed a reducing effect on nitric oxide production of lipopolysaccharide (LPS)-induced RAW 264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in activated RAW 264.7 cells were inhibited by MEB. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that the expression of iNOS and COX-2 mRNA in activated macrophages were suppressed by a high concentration (500 μg/ml) of MEB. Furthermore, a downregulated degradation of IκB-α by MEB was found, indicating that MEB reduced iNOS enzyme expression as a result of preventing NF-κB activation. These results suggest that MEB displays an inhibitory action on biomolecules and has a bioactive action for attenuating excessive NO generation at inflammatory site as well as in cardiovascular disease.

Molecular mechanisms of cartilage destruction: Mechanics, inflammatory mediators, and aging collide

Destruction and loss of articular cartilage is a central feature in most forms of arthritis including the most common form, osteoarthritis (OA). The pathobiologic differences among the various types of arthritis relate, at least in part, to differences in mechanisms driving cartilage destruction. Often forms of arthritis are divided into “inflammatory” and “noninflammatory,” where “inflammatory” arthritis is meant to indicate cellular inflammation resulting from an influx of various activated leukocytes into the joint which mediate destruction, while “noninflammatory” arthritis indicates a lack of significant inflammatory cell invasion and is often described as “degenerative arthritis.” However, as we discover more about the basic mechanisms behind “noninflammatory” or “degenerative arthritis,” it is becoming clear that these are misnomers.

Synthesis, Structure, and Properties of an Fe(II) Carbonyl [(PaPy3)Fe(CO)](ClO4): Insight into the Reactivity of Fe(II)−CO and Fe(II)−NO Moieties in Non-Heme Iron Chelates of N-Donor Ligands

An Fe(II) carbonyl complex [(PaPy3)Fe(CO)](ClO4) (1) of the pentadentate ligand N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide (PaPy3H, H is the dissociable amide proton) has been synthesized and structurally characterized. This Fe(II) carbonyl exhibits its nu(CO) at 1972 cm(-1), and its 1H NMR spectrum in degassed CD3CN confirms its S = 0 ground state. The bound CO in 1 is not photolabile. Reaction of 1 with an equimolar amount of NO results in the formation of the {Fe-NO}7 nitrosyl [(PaPy3)Fe(NO)](ClO4) (2), while excess NO affords the iron(III) nitro complex [(PaPy3)Fe(NO2)](ClO4) (5). In the presence of [Fe(Cp)2]+ and excess NO, 1 forms the {Fe-NO}6 nitrosyl [(PaPy3)Fe(NO)](ClO4)2 (3). Complex 1 also reacts with dioxygen to afford the iron(III) mu-oxo species [{(PaPy3)Fe}2O](ClO4)2 (4). Comparison of the metric and spectral parameters of 1 with those of the previously reported {Fe-NO}6,7 nitrosyls 3 and 2 provides insight into the electronic distributions in the Fe(II)-CO, Fe(II)-NO, and Fe(II)-NO+ bonds in the isostructural series of complexes 1-3 derived from a non-heme polypyridine ligand with one carboxamide group.

Caloric restriction and mitochondrial function in the ageing myocardium

Extension of life span by caloric restriction is assumed to result from retardation of a genetically determined program of ageing, but the new concept of hormesis regards caloric restriction as mild stress, which triggers active, protective reactions with reparative capacities. Here, we discuss two potential hormetic reactions with protective efficacy against dysfunctional mitochondria: restoration of neuregulin signalling by upregulation of erbB receptors and enhanced biogenesis of functionally active mitochondria by an eNOS-dependent mechanism. Mitochondrial ageing is considered to result from a vicious cycle of mitochondrial ROS-formation, ROS-mediated damage of mitochondrial DNA, disproportional respiratory chain composition and thereby additionally enhanced ROS production leading to apoptotic cell loss. Proof-of- principle for such a cycle was obtained from transgenic mice with impaired mitochondrial DNA repair capacity. Indirect arguments suggest this cycle operating also in ageing wild-type mammals, accelerated by downregulation of mitochondrial gene expression in insulin resistance, by inflammatory excess NO formation, and by downregulation of erbB receptors in cardiac ageing and failure. Attenuated neuregulin signalling induces a shift in the splice products of the Bcl-x gene from the antiapoptotic Bcl-xL protein towards the proapoptotic Bcl-xS protein, resulting in mitochondrial dysfunction and apoptosis in cardiomyocytes. Transient caloric restriction upregulates erbB receptors and restores mitochondrial Bcl-x-isoform patterns and mitochondrial dysfunction in the ageing heart.

Iron nitrosyl complexes as models for biological nitric oxide transfer reagents

Owing to the indiscriminate reactivity of the free NO radical, intricate control mechanisms are required for storage, transport and transfer of NO to its various biological targets. Among the proposed storage components are protein-bound thionitrosyls (Rprotein-SNO) and protein-bound dinitrosyl iron complexes. Current knowledge suggests the latter are derived from iron-sulfur cluster degradation in the presence of excess NO. Mobilization of protein-bound NO could involve NO or Fe(NO)2 unit transfer to small serum molecules such as glutathione, free cysteine, or iron-porphyrins. The study reported is of a reaction model which addresses the key steps in NO transfer from a prototypal iron dinitrosyl complex. While the N,N'-bis(2-mercaptoethyl)-N,N'-diazacyclooctane (bme-daco) ligand typically binds in square-planar N2S2 coordination, it also serves as a bidentate dithiolate donor for tetrahedral structures in the preparation of the (H+bme-daco)Fe(NO)2 derivative (Chiang et al., J. Am. Chem. Soc. 126:10867-10874, 2004). The removal of one NO produces the mononitrosyl complex, (bme-daco)Fe(NO), and simplifies studies of NO release mechanisms. We have used heme-type model complexes, Fe or Co porphyrins as NO acceptors, yielding (porphyrin)M(NO), where M is Fe or Co, and monitored reactions by nu(NO) Fourier transform IR spectroscopy. Reaction products were verified by electrospray ionization mass spectrometry. Rudimentary mechanistic studies suggest a role for HNO in the NO release from the dinitrosyl; the mononitrosyl benefits as well from acid catalysis. Other NO uptake complexes such as [(N2S2)Fe]2 [N2S2 is bme-daco or N,N'-bis(2-mercapto-2-methylpropyl)-daco] are shown to form Fe(NO) mononitrosyls with stability and spectroscopic signatures similar to those of the porphyrins.

Possible involvement of NO-mediated oxidative stress in induction of rat forestomach damage and cell proliferation by combined treatment with catechol and sodium nitrite

To clarify the mechanisms underlying forestomach carcinogenesis in rats by co-treatment with catechol and sodium nitrite (NaNO 2), we investigated the involvement of oxidative stress resulting from reaction of the two compounds. Since generation of semiquinone radical, hydroxyl radical ( OH), and peroxynitrite (ONOO −) arose through the reaction of catechol with NO, we proposed that superoxide resulting from catechol oxidation reacted with excess NO, consequently yielding OH via ONOO −. Male F344 rats were co-treated with 0.2% catechol in the diet and 0.8% NaNO 2 in the drinking water for 2 weeks. Prior to occurrence of histological evidence indicating epithelial injury and hyperplasia, 8-hydroxydeoxyguanosine levels in forestomach epithelium significantly increased from 12 h together with appearance of immunohistochemically nitrotyrosine-positive epithelial cells. There were no remarkable changes in rats given each chemical alone. We conclude that oxidative stress due to NO plays an important role in induction of forestomach epithelial damage, cell proliferation, and thus presumably forestomach carcinogenesis.

Improved hepatic glucose production in mice lacking inducible nitric oxide synthase during hyperdynamic septic shock

We recently showed in a hyperdynamic mouse model of septic shock that endogenous glucose production is depressed [1]. However, the mechanism for this depression remains unclear. In this context, the role of excess NO release due to activation of the inducible isoform of the NO synthase (iNOS) has been controversially discussed: while Stadler reported a direct relation between excess NO release and the inhibition of gluconeogenesis [2], other authors did not demonstrate any NO effect [3]. We therefore investigated the effects of genetic iNOS deletion on hepatic glucose production in a clinically relevant murine model of normotensive, hyperdynamic, volume-resuscitated septic shock. Wild-type mice served as controls.

A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock

Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock.

Reactions of Peroxynitrite and Nitrite with Organic Molecules and Hemoglobin

In this work, the reactions of nitrite (NO2-) and peroxynitrite (ONOO-) with organic molecules as well as with hemoglobin (Hb) were examined and the potential interference with the detection of hydrogen peroxide and Hb was investigated. ONOO- at low concentrations (35-140 microM) induced a concentration-dependent oxidation of o-phenylenediamine and guaiacol, and this process can be improved by the addition of Hb in a concentration-dependent manner. This enhancing effect of Hb was possibly due to the formation of such highly reactive species as ferrylHb during the reaction of ONOO- and Hb. NO2- also oxidized the aromatic amine o-phenylenediamine, but its efficiency was much lower than that of ONOO-. A 300-fold excess of NO2- over hydrogen peroxide inhibited the oxidation of Pyrogallol Red mediated by hydrogen peroxide and Hb, which was due in part to the reaction of NO2- with Hb ferryl species compound I and compound II and the phenoxyl radical. These data suggest that ONOO- and NO2- can interfere with the detection of hydrogen peroxide. The overestimation or underestimation of the hydrogen peroxide detected is dependent upon the organic molecule utilized for detection and the relative rate of NO2-, superoxide, and ONOO- generation.

Unusual Role of Solvents in the Syntheses of {Fe−NO}6,7 Nitrosyls Derived from a Ligand with Carboxamido Nitrogen and Thiolato Sulfur Donors

Reaction of excess NO with the S = 3/2 Fe(III) complex (Et4N)2[Fe(PhPepS)(Cl)] (1) in protic solvents such as MeOH affords the {Fe-NO}(7) nitrosyl (Et(4)N)(2)[Fe(PhPepS)(NO)] (2). This distorted square-pyramidal S = 1/2 complex, a product of reductive nitrosylation, is the first example of an {Fe-NO}7 nitrosyl with carboxamido-N and thiolato-S coordination. When the same reaction is performed in aprotic solvents such as MeCN and DMF, the product is a dimeric diamagnetic {Fe-NO}6 complex, (Et4N)2-[{Fe(PhPepS)(NO)}2] (3). Both electrochemical and chemical oxidation of 2 leads to the formation of 3 via a transient five-coordinate {Fe-NO}6 intermediate. The oxidation is NO-centered. The ligand frame is not attacked by excess NO in these reactions.

Intensive insulin therapy protects the endothelium of critically ill patients

The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-kappaB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.

Selective Substrate-Based Inhibitors of Mammalian Dimethylarginine Dimethylaminohydrolase

The enzyme DDAH metabolizes methylarginines that are inhibitors of nitric oxide synthase (NOS). Substrate-based inhibitors of mammalian DDAH have been synthesized, with optimization to give selective inhibition of DDAH with no significant direct effect on NOSs. These are the first examples of reversible DDAH inhibitors with significant activity and selectivity. In vivo administration increases plasma ADMA levels, giving proof of concept that these inhibitors can be used to probe the physiological effects of DDAH inhibition, with potential for pharmaceutical use of DDAH inhibitors in diseases where excess NO production is implicated.

Properties of Chloroformyl Peroxynitrate, ClC(O)OONO2

The synthesis of ClC(O)OONO(2) is accomplished by photolysis of a mixture of Cl(2), NO(2), and CO in large excess of O(2) at about -70 degrees C. The product is isolated after repeated trap-to-trap condensation. The solid compound melts at -84 degrees C, and the extrapolated boiling point is 80 degrees C. ClC(O)OONO(2) is characterized by IR, Raman, (13)C NMR, and UV spectroscopy. According to the IR matrix spectra, the compound exists at room temperature only as a single conformer. The molecular structure of ClC(O)OONO(2) is determined by gas electron diffraction. The molecule possesses a gauche structure with a dihedral angle of phi(COON) = 86.7(19) degrees , and the C=O bond is oriented syn with respect to the O-O bond. The short O-O bond (1.418(6) A) and the long N-O bond (1.511(8) A) are consistent with the facile dissociation of ClC(O)OONO(2) into the radicals ClC(O)OO and NO(2). The experimental geometry of ClC(O)OONO(2) is reproduced reasonably well by B3LYP/6-311+G(2df) calculations, whereas the MP2 approximation predicts the N-O bond considerably too long and the dihedral angle too small.

Reactions of Nitrogen Oxides with Heme Models. Spectral and Kinetic Study of Nitric Oxide Reactions with Solid and Solute FeIII(TPP)(NO3)

The reaction(s) of nitric oxide (nitrogen monoxide) gas with sublimed layers containing the nitrato iron(III) complex Fe(III)(TPP)(eta(2)-O(2)NO) (1, TPP = meso-tetraphenyl porphyrinate(2)(-)) leads to formation of several iron porphyrin species that are ligated by various nitrogen oxides. The eventual products of these low-temperature solid-state reactions are the nitrosyl complex Fe(TPP)(NO), the nitro-nitrosyl complex Fe(TPP)(NO(2))(NO), and 1 itself, and the relative final quantities of these were functions of the NO partial pressure. It is particularly notable that isotope labeling experiments show that the nitrato product is not simply unreacted 1 but is the result of a series of transformations taking place in the layered material. Thus, the nitrato complex formed from solid Fe(TPP)(eta(2)-O(2)NO) maintained under a (15)NO atmosphere was found to be the labeled analogue Fe(TPP)(eta(2)-O(2)(15)NO). The reactivities of the layered solids are compared to the behaviors of the same species in ambient temperature solutions. To interpret the reactions of the labeled nitrogen oxides, the potential exchange reactions between N(2)O(3) and (15)NO were examined, and complete isotope scrambling was observed between these species under the reaction conditions (T = 140 K). Overall it was concluded from isotope labeling experiments that the sequence of reactions is initiated by reaction of 1 with NO to give the nitrato nitrosyl complex Fe(TPP)(eta(1)-ONO(2))(NO) (2) as an intermediate. This is followed by a reaction in the presence of excess NO that is equivalent to the loss of the nitrate radical NO(3)(*)( )()to give Fe(TPP)(NO) as another transient species. A plausible pathway involving NO attack on the coordinated nitrate of 2 resulting in the release of N(2)O(4) concerted with electron transfer to the metal center is proposed.