Sergei V. Lymar

Nitroxyl and its anion in aqueous solutions: spin states, protic equilibria, and reactivities toward oxygen and nitric oxide.

The thermodynamic properties of aqueous nitroxyl (HNO) and its anion (NO−) have been revised to show that the ground state of NO− is triplet and that HNO in its singlet ground state has much lower acidity, pKa(1HNO/3NO−) ≈ 11.4, than previously believed. These conclusions are in accord with the observed large differences between 1HNO and 3NO− in their reactivities toward O2 and NO. Laser flash photolysis was used to generate 1HNO and 3NO− by photochemical cleavage of trioxodinitrate (Angelis anion). The spin-allowed addition of 3O2 to 3NO− produced peroxynitrite with nearly diffusion-controlled rate (k = 2.7 × 109 M−1⋅s−1). In contrast, the spin-forbidden addition of 3O2 to 1HNO was not detected (k ≪ 3 × 105 M−1⋅s−1). Both 1HNO and 3NO− reacted sequentially with two NO to generate N3O\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} as a long-lived intermediate; the rate laws of N3O\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{3}^{-}}}\end{equation*}\end{document} formation were linear in concentrations of NO and 1HNO (k = 5.8 × 106 M−1⋅s−1) or NO and 3NO− (k = 2.3 × 109 M−1⋅s−1). Catalysis by the hydroxide ion was observed for the reactions of 1HNO with both O2 and NO. This effect is explicable by a spin-forbidden deprotonation by OH− (k = 4.9 × 104 M−1⋅s−1) of the relatively unreactive 1HNO into the extremely reactive 3NO−. Dimerization of 1HNO to produce N2O occurred much more slowly (k = 8 × 106 M−1⋅s−1) than previously suggested. The implications of these results for evaluating the biological roles of nitroxyl are discussed.

Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets

Recent evidence indicates that Pseudomonas aeruginosa residing as biofilms in airway mucus of cystic fibrosis (CF) patients is undergoing anaerobic metabolism, a form of growth requiring gene products that are not utilized during aerobic growth. The outer membrane protein, OprF, and the rhl quorum sensing circuit are two previously unrecognized cellular factors that are required for optimal anaerobic biofilm viability. Without OprF, bacteria grow extremely poorly because they lack nitrite reductase activity while lacking rhlR or rhlI forces bacteria to undergo metabolic suicide by overproduction of nitric oxide. Furthermore, anaerobic growth favors maintenance of the mucoid, alginate-overproducing phenotype. Thus, with increasing age of CF patients, mucoid populations predominate, indicating that anaerobic bacteria reside in the inspissated airway mucus. Because many frontline antibiotics used in the treatment of CF airway disease are either ineffective or show reduced efficacy during anaerobic conditions, we propose development of new drugs to combat anaerobic metabolism by P. aeruginosa for more effective treatment of chronic CF lung infections.

Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions

Mucoid, mucA mutant Pseudomonas aeruginosa cause chronic lung infections in cystic fibrosis (CF) patients and are refractory to phagocytosis and antibiotics. Here we show that mucoid bacteria perish during anaerobic exposure to 15 mM nitrite (NO2) at pH 6.5, which mimics CF airway mucus. Killing required a pH lower than 7, implicating formation of nitrous acid (HNO2) and NO, that adds NO equivalents to cellular molecules. Eighty-seven percent of CF isolates possessed mucA mutations and were killed by HNO2 (3-log reduction in 4 days). Furthermore, antibiotic-resistant strains determined were also equally sensitive to HNO2. More importantly, HNO2 killed mucoid bacteria (a) in anaerobic biofilms; (b) in vitro in ultrasupernatants of airway secretions derived from explanted CF patient lungs; and (c) in mouse lungs in vivo in a pH-dependent fashion, with no organisms remaining after daily exposure to HNO2 for 16 days. HNO2 at these levels of acidity and NO2 also had no adverse effects on cultured human airway epithelia in vitro. In summary, selective killing by HNO2 may provide novel insights into the important clinical goal of eradicating mucoid P. aeruginosa from the CF airways.

Water oxidation catalyzed by cobalt(II) adsorbed on silica nanoparticles.

A novel, highly efficient, and stable water oxidation catalyst was prepared by a pH-controlled adsorption of Co(II) on ~10 nm diameter silica nanoparticles. A lower limit of ~300 s(-1) per cobalt atom for the catalyst turnover frequency in oxygen evolution was estimated, which attests to a very high catalytic activity. Electron microscopy revealed that cobalt is adsorbed on the SiO(2) nanoparticle surfaces as small (1-2 nm) clusters of Co(OH)(2). This catalyst is optically transparent over the entire UV-vis range and is thus suitable for mechanistic investigations by time-resolved spectroscopic techniques.

Two-pronged survival strategy for the major cystic fibrosis pathogen, Pseudomonas aeruginosa, lacking the capacity to degrade nitric oxide during anaerobic respiration.

Protection from NO gas, a toxic byproduct of anaerobic respiration in Pseudomonas aeruginosa, is mediated by nitric oxide (NO) reductase (NOR), the norCB gene product. Nevertheless, a norCB mutant that accumulated ∼13.6 μM NO paradoxically survived anaerobic growth. Transcription of genes encoding nitrate and nitrite reductases, the enzymes responsible for NO production, was reduced >50‐ and 2.5‐fold in the norCB mutant. This was due, in part, to a predicted compromise of the [4Fe–4S]2+ cluster in the anaerobic regulator ANR by physiological NO levels, resulting in an inability to bind to its cognate promoter DNA sequences. Remarkably, two O2‐dependent dioxygenases, homogentisate‐1,2‐dioxygenase (HmgA) and 4‐hydroxyphenylpyruvate dioxygenase (Hpd), were derepressed in the norCB mutant. Electron paramagnetic resonance studies showed that HmgA and Hpd bound NO avidly, and helped protect the norCB mutant in anaerobic biofilms. These data suggest that protection of a P. aeruginosa norCB mutant against anaerobic NO toxicity occurs by both control of NO supply and reassignment of metabolic enzymes to the task of NO sequestration.

Medium effects on reactions of the carbonate radical with thiocyanate, iodide, and ferrocyanide ions

Abstract Results are presented which show that there is no pH dependence of the carbonate radical reactivity toward SCN − , I − , and Fe(CN) 6 4− above pH 8.5. It is demonstrated that observations in the literature on these reactions which have been interpreted to show a p K a of 9.5 for the carbonate radical, in disagreement with other reports that the radical is not protonated in this pH region, can be explained by the medium effects. It is also shown that previous studies of the reaction between carbonate radical and thiocyanate are in error, and the mechanism of this reaction is elucidated.

Disproportionation pathways of aqueous hyponitrite radicals (HN2O2(*)/N2O2(*-)).

Pulse radiolysis and flash photolysis are used to generate the hyponitrite radicals (HN2O2(*)/N2O2(*-)) by one-electron oxidation of the hyponitrite in aqueous solution. Although the radical decay conforms to simple second-order kinetics, its mechanism is complex, comprising a short chain of NO release-consumption steps. In the first, rate-determining step, two N2O2(*-) radicals disproportionate with the rate constant 2k = (8.2 +/- 0.5) x 10(7) M(-1) s(-1) (at zero ionic strength) effectively in a redox reaction regenerating N2O2(2-) and releasing two NO. This occurs either by electron transfer or, more likely, through radical recombination-dissociation. Each NO so-produced rapidly adds to another N2O2(*-), yielding the N3O3(-) ion, which slowly decomposes at 300 s(-1) to the final N2O + NO2(-) products. The N2O2(*-) radical protonates with pKa = 5.6 +/- 0.3. The neutral HN2O2(*) radical decays by an analogous mechanism but much more rapidly with the apparent second-order rate constant 2k = (1.1 +/- 0.1) x 10(9) M(-1) s(-1). The N2O2(*-) radical shows surprisingly low reactivity toward O2 and O2(*-), with the corresponding rate constants below 1 x 10(6) and 5 x 10(7) M(-1) s(-1). The previously reported rapid dissociation of N2O2(*-) into N2O and O(*-) does not occur. The thermochemistry of HN2O2(*)/N2O2(*-) is discussed in the context of these new kinetic and mechanistic results.

Beyond fossil fuel–driven nitrogen transformations

Transforming nitrogen without carbon How much carbon does it take to make nitric acid? The counterintuitive answer nowadays is quite a lot. Nitric acid is manufactured by ammonia oxidation, and all the hydrogen to make ammonia via the Haber-Bosch process comes from methane. Thats without even accounting for the fossil fuels burned to power the process. Chen et al. review research prospects for more sustainable routes to nitrogen commodity chemicals, considering developments in enzymatic, homogeneous, and heterogeneous catalysis, as well as electrochemical, photochemical, and plasma-based approaches. Science, this issue p. eaar6611 BACKGROUND The invention of the Haber-Bosch (H-B) process in the early 1900s to produce ammonia industrially from nitrogen and hydrogen revolutionized the manufacture of fertilizer and led to fundamental changes in the way food is produced. Its impact is underscored by the fact that about 50% of the nitrogen atoms in humans today originate from this single industrial process. In the century after the H-B process was invented, the chemistry of carbon moved to center stage, resulting in remarkable discoveries and a vast array of products including plastics and pharmaceuticals. In contrast, little has changed in industrial nitrogen chemistry. This scenario reflects both the inherent efficiency of the H-B process and the particular challenge of breaking the strong dinitrogen bond. Nonetheless, the reliance of the H-B process on fossil fuels and its associated high CO2 emissions have spurred recent interest in finding more sustainable and environmentally benign alternatives. Nitrogen in its more oxidized forms is also industrially, biologically, and environmentally important, and synergies in new combinations of oxidative and reductive transformations across the nitrogen cycle could lead to improved efficiencies. ADVANCES Major effort has been devoted to developing alternative and environmentally friendly processes that would allow NH3 production at distributed sources under more benign conditions, rather than through the large-scale centralized H-B process. Hydrocarbons (particularly methane) and water are the only two sources of hydrogen atoms that can sustain long-term, large-scale NH3 production. The use of water as the hydrogen source for NH3 production requires substantially more energy than using methane, but it is also more environmentally benign, does not contribute to the accumulation of greenhouse gases, and does not compete for valuable and limited hydrocarbon resources. Microbes living in all major ecosystems are able to reduce N2 to NH3 by using the enzyme nitrogenase. A deeper understanding of this enzyme could lead to more efficient catalysts for nitrogen reduction under ambient conditions. Model molecular catalysts have been designed that mimic some of the functions of the active site of nitrogenase. Some modest success has also been achieved in designing electrocatalysts for dinitrogen reduction. Electrochemistry avoids the expense and environmental damage of steam reforming of methane (which accounts for most of the cost of the H-B process), and it may provide a means for distributed production of ammonia. On the oxidative side, nitric acid is the principal commodity chemical containing oxidized nitrogen. Nearly all nitric acid is manufactured by oxidation of NH3 through the Ostwald process, but a more direct reaction of N2 with O2 might be practically feasible through further development of nonthermal plasma technology. Heterogeneous NH3 oxidation with O2 is at the heart of the Ostwald process and is practiced in a variety of environmental protection applications as well. Precious metals remain the workhorse catalysts, and opportunities therefore exist to develop lower-cost materials with equivalent or better activity and selectivity. Nitrogen oxides are also environmentally hazardous pollutants generated by industrial and transportation activities, and extensive research has gone into developing and applying reduction catalysts. Three-way catalytic converters are operating on hundreds of millions of vehicles worldwide. However, increasingly stringent emissions regulations, coupled with the low exhaust temperatures of high-efficiency engines, present challenges for future combustion emissions control. Bacterial denitrification is the natural analog of this chemistry and another source of study and inspiration for catalyst design. OUTLOOK Demands for greater energy efficiency, smaller-scale and more flexible processes, and environmental protection provide growing impetus for expanding the scope of nitrogen chemistry. Nitrogenase, as well as nitrifying and denitrifying enzymes, will eventually be understood in sufficient detail that robust molecular catalytic mimics will emerge. Electrochemical and photochemical methods also demand more study. Other intriguing areas of research that have provided tantalizing results include chemical looping and plasma-driven processes. The grand challenge in the field of nitrogen chemistry is the development of catalysts and processes that provide simple, low-energy routes to the manipulation of the redox states of nitrogen. Possible routes for nitrogen transformations that eliminate or minimize the need for fossil fuels. A more thorough understanding of nitrogenase may lead to more efficient homogeneous catalysts for reduction of N2 to NH3. Coupling of theory and experiment will lead to more effective and stable heterogeneous and electrocatalysts. Innovative energy sources, such as plasmas, which involve nonequilibrium chemistry, may lead to new nitrogen conversion mechanisms. ILLUSTRATION: K. HOLOSKI Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle. These approaches, as well as the challenges involved, are discussed in this Review.

Structural and mechanistic analysis through electronic spectra: aqueous hyponitrite radical (N2O2-) and nitrosyl hyponitrite anion (N3O3-).

Aqueous hyponitrite radical (N(2)O(2)(-)) and nitrosyl hyponitrite anion (N(3)O(3)(-)) are important intermediates in the reductive chemistry of NO. The structures and absorption spectra of various hydrated isomers of these compounds were investigated in this work using high-level quantum mechanical calculations combined with the explicit classical description of the aqueous environment. For N(2)O(2)(-), comparison of the calculated spectra and energetics with the experimental data reveals that (1) upon the one-electron oxidation of trans-hyponitrite (ON═NO(2-)), the trans configuration of the resulting ON═NO(-) radical is preserved; (2) although cis- and trans-ON═NO(-) are energetically nearly equivalent, the barrier for the trans-cis isomerization is prohibitively high because of the partial double character of the NN bond; (3) the calculations confirm that the UV spectrum of ONNO(-) was misinterpreted in the earlier pulse radiolysis work, and its more recent revision has been justified. For the N(3)O(3)(-) ion, the symmetric isomer [Formula: see text] is the dominant observable species, and the asymmetric isomer [Formula: see text] contributes insignificantly to the experimental spectrum. Coherent analysis of the calculated and experimental data suggests a reinterpretation of the N(2)O(2)(-) + NO reaction mechanism according to which the reaction evenly bifurcates to yield both the symmetric and asymmetric isomers of N(3)O(3)(-). While the latter isomer rapidly decomposes to the final NO(2)(-) + N(2)O products, the former isomer is stable toward this decomposition, but its formation is reversible with the homolysis equilibrium constant K(hom) = 2.2 × 10(-7) M. Collectively, these results demonstrate that advanced theoretical modeling can be of significant benefit in structural and mechanistic analysis on the basis of the electronic spectra of aqueous transients.

Hydrogen Atom Reactivity toward Aqueous tert-Butyl Alcohol

Through a combination of pulse radiolysis, purification, and analysis techniques, the rate constant for the H + (CH(3))(3)COH → H(2) + (•)CH(2)C(CH(3))(2)OH reaction in aqueous solution is definitively determined to be (1.0 ± 0.15) × 10(5) M(-1) s(-1), which is about half of the tabulated number and 10 times lower than the more recently suggested revision. Our value fits on the Polanyi-type, rate-enthalpy linear correlation ln(k/n) = (0.80 ± 0.05)ΔH + (3.2 ± 0.8) that is found for the analogous reactions of other aqueous aliphatic alcohols with n equivalent abstractable H atoms. The existence of such a correlation and its large slope are interpreted as an indication of the mechanistic similarity of the H atom abstraction from α- and β-carbon atoms in alcohols occurring through the late, product-like transition state. tert-Butyl alcohol is commonly contaminated by much more reactive secondary and primary alcohols (2-propanol, 2-butanol, ethanol, and methanol), whose content can be sufficient for nearly quantitative scavenging of the H atoms, skewing the H atom reactivity pattern, and explaining the disparity of the literature data on the H + (CH(3))(3)COH rate constant. The ubiquitous use of tert-butyl alcohol in pulse radiolysis for investigating H atom reactivity and the results of this work suggest that many other previously reported rate constants for the H atom, particularly the smaller ones, may be in jeopardy.