Nitrosonium Research Articles

Rapid aqueous-phase dark reaction of phenols with nitrosonium ions: Novel mechanism for atmospheric nitrosation and nitration at low pH.

Dark aqueous-phase reactions involving the nitrosation and nitration of aromatic organic compounds play a significant role in the production of light-absorbing organic carbon in the atmosphere. This process constitutes a crucial aspect of tropospheric chemistry and has attracted growing research interest, particularly in understanding the mechanisms governing nighttime reactions between phenols and nitrogen oxides. In this study, we present new findings concerning the rapid dark reactions between phenols containing electron-donating groups and inorganic nitrite in acidic aqueous solutions with pH levels <3.5. This reaction generates a substantial amount of nitroso- and nitro-substituted phenolic compounds, known for their light-absorbing properties and toxicity. In experiments utilizing various substituted phenols, we demonstrate that their reaction rates with nitrite depend on the electron cloud density of the benzene ring, indicative of an electrophilic substitution reaction mechanism. Control experiments and theoretical calculations indicate that the nitrosonium ion (NO+) is the reactive nitrogen species responsible for undergoing electrophilic reactions with phenolate anions, leading to the formation of nitroso-substituted phenolic compounds. These compounds then undergo partial oxidation to form nitro-substituted phenols through reactions with nitrous acid (HONO) or other oxidants like oxygen. Our findings unveil a novel mechanism for swift atmospheric nitrosation and nitration reactions that occur within acidic cloud droplets or aerosol water, providing valuable insights into the rapid nocturnal formation of nitrogen-containing organic compounds with significant implications for climate dynamics and human health.

Nitrite facilitated transformation of halophenols in ice

This study investigated the expediated transformation of halophenols in the presence of nitrite (NO2−) under slightly acidic conditions in ice, whereas such transformation was negligible in liquid water at 4 °C. We proposed that this phenomenon was attributed to the freeze-concentration effect, incurring a pH drop and the aggregation of NO2− and halophenols within the liquid-like grain boundary layer amid ice crystals. Within this micro-environment, NO2− underwent protonation to generate reactive nitrous acid (HNO2) and nitrosonium ions (NO+) that facilitate the nitration and oxidation of halophenols. When 10 μМ halophenol was treated by freezing in the presence of 5 μМ NO2−, the total yields of nitrated products reached 2.4 μМ and 1.4 μМ within 12 h for 2-chlorophenol (2CP) and 2-bromophenol (2BP), respectively. NO+ drove oxidative coupling reactions, generating hydroxyl polyhalogenated diphenyl ethers (OH-PBDEs) and hydroxyl polyhalogenated diphenyls via C-O or C-C coupling. These two pathways were intricately intertwined. The presence of natural organic matter (NOM) mitigated the formation of nitrated products and completely suppressed the coupling products. This study offers valuable insights into the fate of halophenols in ice and suggests potential pathways for the formation of nitrophenolic compounds and OH-PBDEs in natural cold environments. These findings also open up a new avenue in environmental chemistry research.

Synthesis of Diarylamines via Nitrosonium-Initiated C-N Bond Formation.

Electron-rich diarylamines, exemplified by anisole-derived amines, play pivotal roles in process chemistry, pharmaceuticals, and materials. In this study, homo-diarylamines were synthesized directly from the C-H activation of electron-rich arenes by sodium nitrate/trifluoroacetic acid and the successive treatment of iron powder. Mechanistic investigations reveal that nitrosoarene serves as the reaction intermediate, and the formation of the second C-N bond between the resulting nitrosoarene and electron-rich arene is catalyzed by the nitrosonium ion (NO+). Thus, hetero-diarylamines were synthesized using preformed nitrosoarenes and various electron-rich arenes. This reaction complements a range of cross-coupling reactions catalyzed by transition metal catalysts.

Noncovalent Interactions in Hydrated Nitrosonium Ion Clusters Mediated by Hydrogen-Bonded Water Networks.

As important species in the D region of the ionosphere, hydrated nitrosonium ion clusters [NO+(H2O)n] are also archetypal and concise models to illustrate effects of different solvent shells. We have investigated noncovalent interactions in NO+(H2O)3 and NO+(H2O)4 isomers with high levels of ab initio and symmetry-adapted perturbation theory (SAPT) methods. On the basis of our computations, the exchange energies become much more repulsive, whereas the induction energies are significantly more attractive for the noncovalent interactions of NO+ with hydrogen-bonded water chains. Combined with analyses of the electron densities for the NO+(H2O)3 and NO+(H2O)4 isomers, we propose that the counteracting effect of the exchange and induction energies could be deemed as an index for the tendency to form the HO-NO covalent bond. Moreover, we have also found that the third-order induction terms are very important to evaluate reasonable charge transfer energies with the SAPT computations.

Electrochemical degradation and mineralisation of organic dyes in aqueous nitrate solutions

Electrochemical treatment of organic matter for environmental remediation necessitates the development of cheap and robust electrodes that are chemically and structurally stable. To address this challenging requirement, we demonstrate a new electrochemical approach using a simple copper electrode under cathodic conditions to electrochemically generate reactive nitrosonium ions for the degradation of different classes of synthetic organic dyes. This could be achieved in an aqueous HNO3/KNO3 electrolyte at a relatively low cathodic potential of −0.5 V RHE at room temperature. UV–visible absorption spectroscopy, Raman spectroscopy, liquid chromatography – mass spectrometry and total organic carbon measurements revealed the rapid decolorisation and mineralisation of several dye types such as triarylmethane dyes (crystal violet, cresol red), an azo dye (methyl orange) as well as a sulfur containing thiazine dye (toluidine blue). The total organic carbon content of a 50 mg L−1 methyl orange solution was found to decrease by 83% after 1 h of electrolysis. Promisingly, locally sourced river and creek water samples spiked with 50 mg L−1 methyl orange were also successfully treated for up to 6 cycles at a simple Cu electrode, demonstrating potential for the remediation of polluted waterways.

Pharmacocorrection of Disturbances in the no System in Experimental Chronic Generalized Periodontitis

BACKGROUND: In the light of modern views on the pathogenesis of inflammatory diseases of the oral cavity, a promising direction is the use of agents with metabolitotropic, endothelioprotective, and especially with antioxidant action. AIM: The purpose of this study was to evaluate the effect of a combination of thiotriazoline and L-arginine (1:4) on the parameters of the nitroxidergic system of the blood and periodontium of rats with experimental chronic generalized periodontitis and substantiate further study of this combination. METHODS: Real-time reverse-transcription polymerase chain reaction was used to assess the mRNA expression status of iNOS and nNOS mRNAs. The total content of reduced thiols was also determined by the reaction with Elman’s reagent. RESULTS: We found an increase in the total activity of NOS by 90.01% due to an increase in the expression of iNOS, while a decrease in the expression of its endothelial form was observed (a decrease in the expression of eNOS mRNA by 74.3%) compared with the intact group. An increase in iNOS activity led to an increase in the production of NO, which, under conditions of antioxidant deficiency, is converted into cytotoxic forms (peroxynitrite and nitrosonium ion). CONCLUSIONS: The course administration of Mexidol (250 mg/kg) and, especially, the combination of thiotriazoline and L-arginine (1:4) (200 mg/kg) to animals with CGP, leads to a decrease in the gingival pocket to 6 mm (Mexidol) and to 4 mm against the background almost complete absence of bleeding, swelling, and tooth mobility (combination), and also led to a decrease in iNOS mRNA expression by 65.6% (p &lt; 0.05).

Promotion of S-nitrosation of cysteine by a {Co(NO)2}10 complex.

S-Nitrosothiols (SNOs) serve as endogenous carriers and donors of NO within living cells, releasing nitrosonium ions (NO+), NO, or other nitroso derivatives. In this study, we present a bioinspired {Co(NO)2}10 complex 1 that achieved S-nitrosation towards Cys residues. The incorporation of a ferrocenyl group in 1 allowed for fine-tuning of the nitrosation reaction, taking advantage of the redox ability of Cys residues. Complex 1 was synthesized and characterized, demonstrating its NO translation reactivity. Furthermore, complex 1 successfully converted Cys into S-nitrosocysteine (Cys-SNO), as confirmed by UV-Vis, IR, and XAS spectroscopy. This study presents a promising approach for S-nitrosation of Cys residues for further exploration in the modification of Cys-containing peptides.

Ortho-Naphthoquinone-Catalyzed Aerobic Hydrodeamination of Aryl Amines via in Situ De-diazotization of Aryl Diazonium Species.

The catalytic diazotization of aryl amines was developed using ortho-naphthoquinone catalyst under aerobic conditions, where the 2-nitropropane served as a source of nitrosonium ion. The catalytic generation of diazonium species from aryl amines was further explored in the hydrode-diazotization to give the corresponding products. The mechanistic studies indicated the involvement of aryl radical species that readily underwent the radical cyclization to alkenes as well as the halogen abstraction reactions.

Reactivity of Nitric Oxide and Nitrosonium Ion with Copper(II/I) Schiff Base Complexes: Mechanistic Aspects of Imine C═N Bond Cleavage and Oxidation of Pyridine-2-aldehyde to Pyridine-2-carboxylic Acid.

Four Schiff base ligands of the general formulas [6-(R)-2-pyridyl-N-(2'-methylthiophenyl)methylenimine] (RL1) and 6-p-chlorophenyl-2-pyridyl-N-(2'-phenylthiophenyl)methylenimine (RL2), where R = H, Me, p-ClPh, and their bis-ligand copper(II) and copper(I) complexes, 1-4 and 1'-4', respectively, were synthesized and characterized. The reactivities of 1-4 with nitric oxide (NO) gas and of 1'-4' with solid NOBF4 (NO+) were examined in dry acetonitrile in the presence and absence of water (H2O). The results revealed that, in the absence of H2O, complexes 1-4 (or 1'-4') reacts with NO (or NOBF4), leading to imine C═N bond cleavage of both (or one) Schiff base(s) that generates 2 (or 1) equiv of 2-(methyl/phenyl)thiobenzenediazonium perchlorates (5/6) and the corresponding picolaldehyde (RPial) via a copper nitrosyl of a {CuNO}10-type intermediate. In the presence of H2O, the in situ formed RPial get oxidized to the corresponding picolinic acid (RPicH) via an in situ formed LCuIOH intermediate (LCuI + HO-NO → LCuIOH + NO+; L = RL1/RL2/RPic- and νO-H of CuIOH = 3650 cm-1) and subsequently produces, with the aid of NO+ oxidant, the picolinate-ligated copper(II) complexes (i) [(HPic)2Cu] (7), [(MePic)4Cu3(NO3)2]n·H2O (8·H2O), or [(ClPhPic)2Cu] (9) when NO reacts with 1-4 or (ii) [(RPic)CuII(RL1/RL2)]+ when NO+ reacts with 1'-4'. The CuII to CuI reduction of [(RPic)CuII(RL1/RL2)]+ is essential for C═N cleavage of the remaining RL1/RL2 Schiff base; excess NO can do it. The X-ray structures (1, 1', 3', 5, 7, and 8) and spectroscopic results revealed the role of CuII/I, NO, NO+, and H2O, shedding light on the mechanism of C═N bond cleavage and the oxidation of pyridine-2-aldehyde to pyridine-2-carboxylic acid. The reaction of 1 with 15NO revealed that the terminal N of the N2+ group of 5 originates from 15NO [ν14N14N- = 2248 cm-1 and ν15N14N- = 2212 cm-1].

S-nitrosothiols signaling in cystic fibrosis airways

S-nitrosothiols (SNOs) are small naturally occurring thiol and nitric oxide adducts that participate in many cell signaling pathways in living organisms. SNOs receive widespread attention in cell biology, biochemistry and chemistry because they can donate nitric oxide and/or nitrosonium ions in S-nitrosylation reactions, which are comparable to phosphorylation, acetylation, glutathionylation, and palmitoylation reactions. SNOs have advantageous effects in respiratory diseases and other systems in the body. S-nitrosylation signaling is a metabolically regulated physiological process that leads to specific post-translational protein modifications. S-nitrosylation signaling is faulty in cystic fibrosis (CF) and many other lung diseases. CF is an inherited, lethal autosomal recessive multisystem disease resulting from mutations in the gene encoding the CF transmembrane conductance regulatory (CFTR) protein. F508del CFTR is the most common mutation associated with CF, which results in CFTR misfolding because a phenylalanine is deleted from the primary structure of CFTR. The majority of wild-type CFTR and almost all F508del is degraded before reaching the cell surface. Ultimately, CF researchers have been looking to correct the mutated CFTR protein in the CF patients. Remarkably, researchers have found that SNOs levels are low in the CF lower airway compared to non-CF patients. We have been interested in determining whether SNOs increase CFTR maturation through S-nitrosylation. Maturation of both wild type and mutant F508del CFTR increases SNOs, which up-regulate CFTR maturation. In this review, we summarized our current knowledge of S-nitrosothiols signaling in cystic fibrosis airways.

Structural Changes in Cell-Wall and Cell-Membrane Organic Materials Following Exposure to Free Nitrous Acid.

Previous studies demonstrate that free nitrous acid (FNA, i.e., HNO2) is biocidal for a range of microorganisms. The biocidal mechanisms of FNA are largely unknown. In this work, it is hypothesized that FNA will break bonds in molecules found in the cell envelope, thus causing cell lysis. Selected molecules representing components found in the cell envelope were treated with FNA at 6.09 mg N/L (NO2- = 250 mg N/L, pH 5.0) for 24 h (conditions typically used in applications) to evaluate the hypothesized chemical interactions. Molecular changes were observed using analytical techniques including proton (1H) nuclear magnetic resonance spectroscopy (NMR) and electrospray ionization mass spectrometry (ESI-MS). It was found that FNA broke down a range of cell envelope molecules. The spectral data demonstrated that the FNA reactions proceeded via two general pathways. One consisted of electrophilic substitution, whereby the nitrosonium ion (NO+) was the reactive electrophile. The other was via oxidative reactions involving nitrogen radicals (e.g., •NO2 and •NO) formed from the decomposition of FNA. We further revealed that it was HNO2 that caused the breakdown, rather than the exclusive action of the acid (H+) or nitrite (NO2-) counterparts. The fragmentation of these representative cell envelope molecules provides insight into the biocidal effects of FNA on microorganisms.

Oxidative nitration reaction of antiaromatic 5,15-dioxaporphyrin

Upon oxidation of 20[Formula: see text]-electron antiaromatic 5,15-dioxaporphyrin (DOP) using nitrosonium ions as oxidants, a tetrakis-[Formula: see text]-nitrated compound was formed instead of the expected 18[Formula: see text]-electron aromatic dication species via an oxidative nitration reaction mechanism. Compared with the original DOP, this tetranitro DOP product exhibited a blue shift of absorption and downfield shifts of the [Formula: see text]-pyrrolic proton signals. The unique antiaromatic electronic structure of the tetranitro DOP was disclosed experimentally by electrochemistry and theoretically by DFT and NICS calculations.

3+2] cycloaddition reaction of metallacyclopropene with nitrosonium ion: isolation of aromatic metallaisoxazole.

The synthesis of metallaisoxazole by the [3+2] cycloaddition reaction of metallacyclopropene with nitrosonium tetra-fluoroborate has been achieved under mild conditions. Nuclear magnetic resonance spectra, X-ray crystallographic analysis, and density functional theory calculations all suggest that the metallaisoxazole exhibits an aromatic character.

Nitric Oxide: The Key Molecule for Polyphenols Antimicrobial Action

The role of hydroxycinnamic acids as antioxidants, in vivo, has been widely discussed, but, recently, a great debate has focused on their antimicrobial action. In general, for the hydroxycinnamic acids’ action, the presence of NO, which is known to be an antimicrobial agent, seems compulsory; its production goes through the intermediacy of the nitrosonium ion, and a very low pH, for instance, as in the stomach, is requested. However, the action of the hydroxycinnamic acids seems to take place even in different biological compartments, i.e., characterized by different pHs and conditions, and then, for NO production, an alternative mechanism could be involved. In this light, evidence for the NO formation, via an E.T. mechanism, even in mildly acidic conditions (pH = 6.4), was obtained by reacting an aqueous buffer solution of acidic nitrite (HNO2) with the hydroxycinnamic acids ferulic, caffeic, p-coumaric and sinapic. Experiments conducted by EPR spectroscopy, let to detect the NO formation, and the efficiency of the process depending on the available amount of free polyphenol, and the intrinsic nature of the hydroxycinnamic acids. Thus, the production of NO through a non-enzymatic mechanism, in light acidic conditions, would account for the antimicrobial action of hydroxycinnamic acids, even in unconventional biological compartments, and for NO as the key-molecule.

The Antitumor Properties of Dinitrosyl Iron Complexes with Thiol-Containing Ligands and S-Nitrosoglutathione in Experiments

Abstract—The antitumor activity of S-nitrosoglutathione, bi- and mononuclear dinitrosyl iron complexes with different thiol-containing ligands such as glutathione, mercaptosuccinate, and thiosulfate was studied in models of transplantable murine solid tumors (Lewis lung carcinoma, Acatol adenocarcinoma, and Ca-755 adenocarcinoma). The highest antitumor activity, that is, 90% inhibition of tumor cell growth, was shown by the preparations of dinitrosyl iron complexes with glutathione via intravenous injection (Lewis lung carcinoma) and S-nitrosoglutathione via intraperitoneal injection (Ca-755 adenocarcinoma) to animals. Considering these results together with previous data on the antitumor activity of this type of compound, as well as the results of other researchers in this field, we hypothesized that the antitumor effect is mainly caused by the ability of these compounds to act as donors of nitrosonium ions. Nitrosonium ion-induced S-nitrosation of thiol-containing proteins on the surface of tumor cells leads to an increase in the intracellular oxidative capacity, thus promoting apoptosis and death of tumor cells.

What is the Mechanism of Nitric Oxide Conversion into Nitrosonium Ions Ensuring S-Nitrosating Processes in Living Organisms.

Here, I present the data testifying that the conversion of free radical NO molecules to nitrosonium ions (NO+), which are necessary for the realization of one of NO biological effects (S-nitrosation), may occur in living organisms after binding NO molecules to loosely bound iron (Fe2+ ions) with the subsequent mutual one-electron oxidation-reduction of NO molecules (their disproportionation). Inclusion of thiol-containing substances as iron ligands into this process prevents hydrolysis of NO+ ions bound to iron thus providing the formation of stable dinitrosyl iron complexes (DNIC) with thiol ligands. Such complexes act in living organisms as donors of NO and NO+, providing stabilization and transfer of these agents via the autocrine and paracrine pathways. Without loosely bound iron (labile iron pool) and thiols participating in the DNIC formation, NO functioning as one of universal regulators of diverse metabolic processes would be impossible.

Nitrosonium Reactivity of (NHC)Copper(I) Sulfide Complexes.

This study examines the reactivity of a series of copper(I) sulfide complexes stabilized by the expanded-ring N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)-4,5,6,7-tetrahydro-1,3-diazepin-2-ylidene (7Dipp) toward the nitrosonium ion (NO+). 7Dipp is shown to support neutral sulfide- and disulfide-bridged dicopper(I) complexes, as well as mononuclear copper(I) hydrosulfide. The addition of NO+ to each of these results in the formation of NHC-supported copper(I) cations and elemental sulfur. Reduction of copper(I) to copper(0) is observed upon reaction of NO+ with dicopper(I) sulfide or disulfide, whereas ammonium ion formation is observed upon reaction of copper(I) hydrosulfide with NO+. Ammonium ion formation is likewise observed upon reaction of NO+ with (7Dipp)copper(I) hydride.

Abiotic Formation of Humic-Like Substances through Freezing-Accelerated Reaction of Phenolic Compounds and Nitrite.

A previously unknown abiotic humification pathway which is highly accelerated in frozen solution containing phenolic compounds and nitrite was investigated and proposed. The production of humic-like acids (HLA) and fulvic-like acids (FLA) was observed in the frozen solution (-20 °C) whereas it was negligible in aqueous solution (20 °C). Inorganic nitrogen was transformed into organic nitrogen during the humification process. Mass spectrometry (MS) and elemental analyses, including pyrolysis-GC/MS and FT-ion cyclotron resonance/MS, showed that humification products (HLA and FLA) have chemical structures and compositions similar to nature humic substances. The enhanced humification reaction could be attributed to the freeze-concentration effect, whereby nitrite ions in the unfrozen grain boundary region are transformed into nitrosonium ions which oxidize phenols to phenolic radicals. Confocal Raman microscopy confirmed that catechol and nitrite ions are preferentially concentrated at the ice grain boundary and electron paramagnetic resonance spectroscopic analysis of catechol/nitrite solution detected the phenolic radicals only in frozen solution, not in aqueous solution. The freezing-induced generation of phenolic radicals should lead to the formation of humic-like substances through polymerization. This study identifies and proposes a new humic formation pathway that might work as a model abiotic "bottom-up" mechanism in frozen environmental conditions.

Nitrosonium Ions as Constituents of Dinitrosyl Iron Complexes with Glutathione Responsible for their S-Nitrosating Activity

Nitrosonium Ions as Constituents of Dinitrosyl Iron Complexes with Glutathione Responsible for their S-Nitrosating Activity

Low Temperature NOx Adsorption Study on Pd-Promoted Zeolites

In this study Pd-promoted zeolites (BEA, FER, MFI and MOR) are synthesized and investigated for potential use in the low-temperature NOx adsorption. The catalysts are characterized by BET, XRD, UV–Vis and XRF, while the adsorption/desorption characteristics of the samples are investigated by NOx adsorption/TPD, with and without water in the feed. The nature of the adsorbed NOx species has been analyzed by operando FT-IR spectroscopy. Under dry conditions at 50 °C all the investigated zeolite frameworks are able to store significant amounts of NOx, up to 1 mmol/gcat for the MOR sample; the presence of Pd has not a significant impact on the amounts of the stored NOx. In fact, under dry conditions at 50 °C the zeolite frameworks oxidize NO to NO2, and store NOx from NO2 over the zeolitic support. FTIR data indicates that NOx are stored in the form of nitrosonium ion NO+ and nitrate ions; nitrosyl species formed on Al3+ and Pdn+ sites have also been observed, although to a lower extent. Evidences have also been provided for the existence of gaseous/weakly interacting species (mostly NO2) contained in the pores of the zeolites. Water inhibits NO oxidation over all investigated samples, resulting in a strong decrease in the NOx storage capacity. Still, appreciable amounts of NOx could be stored at 50 °C (up to 60 µmol/gcat for Pd/MFI) in the presence of water over the Pd-doped carriers.