Solvated Electron in Acetonitrile: Radiation Yield, Absorption Spectrum, and Equilibrium between Cavity- and Solvent-Localized States.

The equilibrium between a solvent cavity-localized electron, ecav-, and a dimeric solvent anion, (CH3CN)2•-, which are the two lowest energy states of the solvated electron in acetonitrile, has been investigated by pulse radiolysis at 233-353 K. The enthalpy and entropy for the ecav- to (CH3CN)2•- conversion amount to -11.2 ± 0.3 kcal/mol and -39.3 ± 1.2 cal/(mol K), corresponding to a 0.44 ± 0.35 equilibrium constant at 25 °C. The radiation yield of the solvated electron has been quantified using a Co(II) macrocycle that scavenges electrons with a 1.55 × 1011 M-1 s-1 rate constant. The apparent yield increases without saturation over the attainable scavenger concentration range, reaching 2.8 per 100 eV; this value represents the lower limit for the acetonitrile ionization yield in pulse radiolysis. The apparent molar absorption coefficient of (20.8 ± 1.5) × 103 M-1 cm-1 at 1450 nm and 20 °C for the solvated electron and individual vis-near-infrared (NIR) absorption spectra of ecav- and (CH3CN)2•- are derived from the data. Variances with previous reports are thoroughly discussed. Collectively, these results resolve several controversies concerning the solvated electron properties in acetonitrile and furnish requisite data for quantitative pulse radiolysis investigations in this commonly used solvent.

Hydrogen bonding between hydroxylic donors and MLCT-excited Ru(bpy)2(bpz)2+ complex: implications for photoinduced electron-proton transfer.

The equilibrium constants of the hydrogen bonding (HB) between hydroxylic donors, ROH, and an MLCT-excited Ru(bpy)2(bpz)2+ complex, 1(T), correlated with ROH empirical HB acidities, which could be used for evaluating the unimolecular rate constants of concerted electron-proton transfer within the H-bonded phenol-1(T) exciplexes.

Carbon dioxide-catalyzed peroxynitrite reactivity - The resilience of the radical mechanism after two decades of research.

Peroxynitrite, ONOO-, formed in tissues that are simultaneously generating NO• and O2•-, is widely regarded as a major contributor to oxidative stress. Many of the reactions involved are catalyzed by CO2 via formation of an unstable adduct, ONOOC(O)O-, that undergoes O-O bond homolysis to produce NO2• and CO3•- radicals, whose yields are equal at about 0.33 with respect to the ONOO- reactant. Since its inception two decades ago, this radical-based mechanism has been frequently but unsuccessfully challenged. The most recent among these [Serrano-Luginbuehl et al. Chem. Res. Toxicol.31:721-730; 2018] claims that ONOOC(O)O- is stable, predicts a yield of NO2•/CO3•- of less than 0.01 under physiological conditions and, contrary to widely accepted viewpoints, suggests that radical generation is inconsequential to peroxynitrite-induced oxidative damage. Here we review the experimental and theoretical evidence that support the radical model and show this recently proposed alternative mechanism to be incorrect.

Solvent-dependent transition from concerted electron-proton to proton transfer in photoinduced reactions between phenols and polypyridine Ru complexes with proton-accepting sites.

The bimolecular rate coefficients (kobsq) for quenching the metal-to-ligand charge transfer excited states of two Ru polypyridine complexes containing H-bond accepting sites by six p-substituted phenols exhibit abrupt deviations from the expected linear correlations of log kobsq with phenol's Hammett σp constant. This pattern is attributed to a transition of the quenching mechanism from a concerted electron-proton transfer (EPT) to a proton transfer (PT); the latter becomes predominant for the most acidic phenols in acetonitrile, but not in dichloromethane. This assertion is supported by a detailed thermochemical analysis, which also excludes the quenching pathways involving electron transfer from phenols with or without deprotonation of phenols to the solvent, either concerted or sequential. The transition from EPT to PT upon the σp increase is consistent/supported by the magnitudes of the measured and computed PhOH/OD kinetic isotope effects and by the observed reduction of the EPT product yields upon replacing the low σp methoxyphenol by the high σp nitrophenol. In addition to modulating the relative contribution of the EPT and PT quenching pathways, the solvent strongly affects the bimolecular rate coefficients for the EPT quenching proper. Unlike with H-atom transfer reactions, this kinetic solvent effect could not be quantitatively accounted for by the phenol-solvent H-bonding alone, which suggests a solvent effect on the H-bonding constants in the phenol-Ru complex precursor exciplexes and/or on the unimolecular EPT rate coefficients within these exciplexes.

Beyond fossil fuel-driven nitrogen transformations.

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.

Radiolytic formation of the carbon dioxide radical anion in acetonitrile revealed by transient IR spectroscopy.

The solvated electron in CH3CN is scavenged by CO2 with a rate constant of 3.2 × 1010 M-1 s-1 to produce the carbon dioxide radical anion (CO2˙-), a strong and versatile reductant. Using pulse radiolysis with time-resolved IR detection, this radical is unambiguously identified by its absorption band at 1650 cm-1 corresponding to the antisymmetric CO2˙- stretch. This assignment is confirmed by 13C isotopic labelling experiments and DFT calculations. In neat CH3CN, CO2˙- decays on a ∼10 µs time scale via recombination with solvent-derived radicals (R˙) and solvated protons. Upon addition of formate (HCO2-), the radiation yield of CO2˙- is substantially increased due to H-atom abstraction by R˙ from HCO2- (R˙ + HCO2- → RH + CO2˙-), which occurs in two kinetically separated steps. The rapid step involves the stronger H-abstracting CN˙, CH3˙, and possibly, H˙ primary radicals, while the slower step is due to the less reactive, but more abundant radical, CH2CN˙. The removal of solvent radicals by HCO2- also results in over a hundredfold increase in the CO2˙- lifetime. CO2˙- scavenging experiments suggest that at 50 mM HCO2-, about 60% of the solvent-derived radicals are engaged in CO2˙- generation. Even under CO2 saturation, no formation of the radical adduct, (CO2)2˙-, could be detected on the microsecond time scale.

Role of Hydrogen Bonding in Photoinduced Electron-Proton Transfer from Phenols to a Polypyridine Ru Complex with a Proton-Accepting Ligand.

Electron-proton transfer (EPT) from phenols to a triplet metal-to-ligand charge transfer (MLCT)-excited Ru polypyridine complex containing an uncoordinated nitrogen site, 1(T), can be described by a kinetic model that accounts for the H-bonding of 1(T) to phenol, 1(T) to solvent, and phenol to solvent. The latter plays a major role in the kinetic solvent effect and commonly precludes simultaneous determination of the EPT rate constant and 1(T)-phenol H-bonding constant. A number of these quantities previously reported for similar systems are shown to be in error due to inconsistent data analysis. Control experiments replacing either 1(T) by its structural isomer with a sterically screened nitrogen site or phenol by its H-bonding surrogate, trifluoroethanol, and the observation of negative activation enthalpies for the overall reactions between 1(T) and phenols lend support to the proposed model and provide evidence for the formation of a precursor H-bonded complex between the reactants, which is a prerequisite for EPT.

Mechanistic Insight into Peroxydisulfate Reactivity: Oxidation of the cis,cis-[Ru(bpy)2(OH2)]2O(4+) "Blue Dimer".

One-electron oxidation of the µ-oxo dimer (cis,cis-[Ru(III)(bpy)2(OH2)]2O(4+), {3,3}) to {3,4} by S2O8(2-) can be described by three concurrent reaction pathways corresponding to the three protic forms of {3,3}. Free energy correlations of the rate constants, transient species dynamics determined by pulse radiolysis, and medium and temperature dependencies of the alkaline pathway all suggest that the rate-determining step in these reactions is a strongly nonadiabatic dissociative electron transfer within a precursor ion pair leading to the {3,4}|SO4(2-)|SO4(•-) ion triple. As deduced from the SO4(•-) scavenging experiments with 2-propanol, the SO4(•-) radical then either oxidizes {3,4} to {4,4} within the ion triple, effecting a net two-electron oxidation of {3,3}, or escapes in solution with ∼25% probability to react with additional {3,3} and {3,4}, that is, effecting sequential one-electron oxidations. The reaction model presented also invokes rapid {3,3} + {4,4} → 2{3,4} comproportionation, for which kcom ∼5 × 10(7) M(-1) s(-1) was independently measured. The model provides an explanation for the observation that, despite favorable energetics, no oxidation beyond the {3,4} state was detected. The indiscriminate nature of oxidation by SO4(•-) indicates that its fate must be quantitatively determined when using S2O8(2-) as an oxidant.

Decomposition of amino diazeniumdiolates (NONOates): molecular mechanisms.

Although diazeniumdiolates (X[N(O)NO](-)) are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release NO and/or its congeneric nitroxyl, the mechanisms of these processes remain obscure. In this work, we used a combination of spectroscopic, kinetic, and computational techniques to arrive at a quantitatively consistent molecular mechanism for decomposition of amino diazeniumdiolates (amino NONOates: R2N[N(O)NO](-), where R=N(C2H5)2 (1), N(C3H4NH2)2 (2), or N(C2H4NH2)2 (3)). Decomposition of these NONOates is triggered by protonation of their [NN(O)NO](-) group with the apparent pKa and decomposition rate constants of 4.6 and 1 s(-1) for 1; 3.5 and 0.083 s(-1) for 2; and 3.8 and 0.0033 s(-1) for 3. Although protonation occurs mainly on the O atoms of the functional group, only the minor R2N(H)N(O)NO tautomer (population ~10(-7), for 1) undergoes the NN heterolytic bond cleavage (kd~10(7) s(-1) for 1) leading to amine and NO. Decompositions of protonated amino NONOates are strongly temperature-dependent; activation enthalpies are 20.4 and 19.4 kcal/mol for 1 and 2, respectively, which includes contributions from both the tautomerization and bond cleavage. The bond cleavage rates exhibit exceptional sensitivity to the nature of R substituents which strongly modulate activation entropy. At pH<2, decompositions of all three NONOates that have been investigated are subject to additional acid catalysis that occurs through di-protonation of the [NN(O)NO](-) group.

Mechanism of the formation of a Mn-based CO2 reduction catalyst revealed by pulse radiolysis with time-resolved infrared detection.

Using a new technique, which combines pulse radiolysis with nanosecond time-resolved infrared (TRIR) spectroscopy in the condensed phase, we have conducted a detailed kinetic and mechanistic investigation of the formation of a Mn-based CO2 reduction electrocatalyst, [Mn((t)Bu2-bpy)(CO)3]2 ((t)Bu2-bpy = 4,4'-(t)Bu2-2,2'-bipyridine), in acetonitrile. The use of TRIR allowed, for the first time, direct observation of all the intermediates involved in this process. Addition of excess [(n)Bu4N][HCO2] to an acetonitrile solution of fac-MnBr((t)Bu2-bpy)(CO)3 results in its quantitative conversion to the Mn-formate complex, fac-Mn(OCHO)((t)Bu2-bpy)(CO)3, which is a precatalyst for the electrocatalytic reduction of CO2. Formation of the catalyst is initiated by one-electron reduction of the Mn-formate precatalyst, which produces the bpy ligand-based radical. This radical undergoes extremely rapid (τ = 77 ns) formate dissociation accompanied by a free valence shift to yield the five-coordinate Mn-based radical, Mn(•)((t)Bu2-bpy)(CO)3. TRIR data also provide evidence that the Mn-centered radical does not bind acetonitrile prior to its dimerization. This reaction occurs with a characteristically high radical-radical recombination rate (2kdim = (1.3 ± 0.1) × 10(9) M(-1) s(-1)), generating the catalytically active Mn-Mn bound dimer.

Anomalous reactivity of ceric nitrate in ruthenium "blue dimer"-catalyzed water oxidation.

At high concentrations, nitrate ion alters the dynamics of ruthenium "blue dimer"-catalyzed water oxidation by Ce(IV) such that the oxidation rate is enhanced and a unique reaction intermediate accumulates. This intermediate is characterized by distinct EPR, optical, and resonance Raman (RR) spectra, with the appearance in the latter of a new oxygen isotope-sensitive band. Both Ce(IV) and nitrate are required to generate this intermediate, which suggests ceric-nitrate complexes as the causative agents. Use of (18)O-labeled and (15)N-labeled materials has established that (1) the new RR band is not an O-O stretching mode (for example, as might be associated with a peroxo species) but involves the O atom coordinated to a Ru center, and (2) the O(2) product does not contain an O atom derived from nitrate, eliminating several plausible pathways involving O-atom transfer to oxidized dimer. Although these results are surprising, similar phenomena have been reported for water oxidation catalyzed by monomeric Ru complexes. The dramatic effects observed for the "blue dimer" make it an ideal candidate for further study.

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.

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 ß-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.

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.

Characterization of intermediary redox states of the water oxidation catalyst, [Ru(bpy)(2)(OH(2))](2)O(4+).

Higher oxidation states of the mu-oxo bridged ruthenium "blue dimer" ([Ru(bpy)(2)(OH(2))](2)O(4+)) have been characterized by redox titration measurements, resonance Raman (RR) spectroscopy, EPR spectrometry, and pulse radiolysis. The cumulative results indicate that the progression of accessible oxidation states in acidic media is {3,3} --> {3,4} --> {4,4} --> {5,5}, but changes to {3,3} --> {3,4} --> {4,5} --> {5,5} above pH 2. Although the reaction 2{4,5} + 2H(2)O --> 2{3,4} + O(2) is thermodynamically favorable, no O(2) was detected during the decay of {4,5} to {3,4}. One-electron oxidation of {3,4} by radiolytically generated sulfate and carbonate radicals allowed determination of the {4,4} optical spectrum in neutral and alkaline media, where it exists only as a short-lived transient species. This spectrum was identical to that previously reported for {4,4} in acidic media; this observation and comparative RR spectra suggest that its molecular formula is [Ru(bpy)(2)(OH)](2)O(4+), that is, both Ru atoms contain a coordinated hydroxo ligand. Upon application of an acidic pH jump, electrochemically prepared {4,5} underwent disproportionation to {4,4} and {5,5}, as determined from changes in the EPR spectra of the solutions. These studies clarify the nature of redox transients formed during water oxidation catalysis by the "blue dimer", thereby providing information that is critical to performing accurate mechanistic analyses.

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.

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 approximately 13.6 microM 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 O(2)-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.

Rate and driving force for protonation of aryl radical anions in ethanol.

Aryl radical anions created in liquid alcohols decay on the microsecond time scale by transfer of protons from the solvent. This paper reports a 4.5 decade range of rate constants for proton transfer from a single weak acid, ethanol, to a series of unsubstituted aryl radical anions, Ar-*. The rate constants correlate with free energy change, DeltaG(o), despite wide variations in the two factors that contribute to DeltaG(o): (a) the reduction potentials of the aryls and (b) the Ar-H* bond strengths in the product radicals. For aryl radical anions containing CH2OH substituents, such as 2,2'-biphenyldimethanol*- which is protonated with a rate constant of 3x10(9) s(-1), the faster rates do not fit well in the free energy correlation, suggesting a change in mechanism.

Photoinduced release of nitroxyl and nitric oxide from diazeniumdiolates.

Aqueous photochemistry of diazen-1-ium-1,2,2-triolate (Angeli's anion) and (Z)-1[N-(3-aminopropyl)-N-(3-aminopropyl)amino]diazen-1-ium-1,2-diolate (DPTA NONOate) has been investigated by laser kinetic spectroscopy. In neutral aqueous solutions, 266 nm photolysis of these diazeniumdiolates generates a unique spectrum of primary products including the ground-state triplet (3NO-) and singlet (1HNO) nitroxyl species and nitric oxide (NO*). Formation of these spectrophotometrically invisible products is revealed and quantitatively assayed by analyzing a complex set of their cross-reactions leading to the formation of colored intermediates, the N2O2*- radical and N3O3- anion. The experimental design employed takes advantage of the extremely slow spin-forbidden protic equilibration between 3NO- and 1HNO and the vast difference in their reactivity toward NO*. To account for the kinetic data, a novel combination reaction, 3NO-+1HNO, is introduced, and its rate constant of 6.6x10(9) M-1 s-1 is measured by competition with the reduction of methyl viologen by 3NO-. The latter reaction occurring with 2.1x10(9) M-1 s-1 rate constant and leading to the stable, colored methyl viologen radical cation is useful for detection of 3NO-. The distributions of the primary photolysis products (Angeli's anion: 22% 3NO-, 58% 1HNO, and 20% NO*; DPTA NONOate: 3% 3NO-, 12% 1HNO, and 85% NO*) show that neither diazeniumdiolate is a highly selective photochemical generator of nitroxyl species or nitric oxide, although the selectivity of DPTA NONOate for NO* generation is clearly greater.

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.