15N CIDNP study of formation and decay of peroxynitric acid: evidence for formation of hydroxyl radicals

The reaction of nitrous acid with hydrogen peroxide leads to nitric acid as the only stable product. In the course of this reaction, peroxynitrous acid (ONOOH) and, in the presence of CO(2), a peroxynitrite-CO(2) adduct (ONOOCO(2)(-)) are intermediately formed. Both intermediates decompose to yield highly oxidizing radicals, which subsequently react with excess hydrogen peroxide to yield peroxynitric acid (O(2)NOOH) as a further intermediate. During these reactions, (15)N chemically induced dynamic nuclear polarization (CIDNP) effects are observed, the analysis of the pH dependency of which allows the elucidation of mechanistic details. The formation and decay of peroxynitric acid via free radicals NO(2)(*) and HOO(*) is demonstrated by the appearance of (15)N CIDNP leading to emission (E) in the (15)N NMR signal of O(2)NOOH during its formation and to enhanced absorption (A) during its decay reaction. Additionally, the (15)N NMR signal of the nitrate ion (NO(3)(-)) appears in emission at pH approximately 4.5. These observations are explained by proposing the intermediate formation of short-lived radical anions O(2)NOOH(*)(-) probably generated by electron transfer between peroxynitric acid and peroxynitrate anion, followed by decomposition of O(2)NOOH(*)(-) into NO(3)(-) and HO(*) and NO(2)(-) and HOO(*) radicals, respectively. The feasibility of such reactions is supported by quantum-chemical calculations at the CBS-Q level of theory including PCM solvation model corrections for aqueous solution. The release of free HO(*) radicals during decomposition of O(2)NOOH is supported by (13)C and (1)H NMR product studies of the reaction of preformed peroxynitric acid with [(13)C(2)]DMSO (to yield the typical "HO(*) products" methanesulfonic acid, methanol, and nitromethane) and by ESR spectroscopic detection of the HO(*) and CH(3)(*) radical adducts to the spin trap compound POBN in the absence and presence of isotopically labeled DMSO, respectively.     

15N Chemically Induced Dynamic Nuclear Polarization (15N‐CIDNP) Investigations of the Peroxynitrite Decay and Nitration of N‐Acetyl‐L‐tyrosine

During the decay of (¹⁵N)peroxynitrite (O?¹⁵NOO ^? ) in the presence of N‐acetyl‐L ‐tyrosine (Tyrac) in neutral solution and at 268 K, the ¹⁵N‐NMR signals of ¹⁵NO and ¹⁵NO show emission (E) and enhanced absorption (A) as it has already been observed by Butler and co‐workers in the presence of L ‐tyrosine (Tyr). The effects are built up in radical pairs [CO , ¹⁵NO ]^S formed by O? O bond scission of the (¹⁵N)peroxynitrite? CO₂ adduct (O?¹⁵NO? OCO ). In the absence of Tyrac and Tyr, the peroxynitrite decay rate is enhanced, and ¹⁵N‐CIDNP does not occur. This is explained by a chain reaction during the peroxynitrite decay involving N₂O₃ and radicals NO ^. and NO . The interpretation is supported by ¹⁵N‐CIDNP observed with (¹⁵N)peroxynitrite generated in situ during reaction of H₂O₂ with N‐acetyl‐N‐(¹⁵N)nitroso‐dl ‐tryptophan ((¹⁵N)NANT) at 298 K and pH 7.5. In the presence of Na¹⁵NO₂ at pH 7.5 and in acidic solution, ¹⁵N‐CIDNP appears in the nitration products of Tyrac, 1‐(¹⁵N)nitro‐N‐acetyl‐L ‐tyrosine (1‐¹⁵NO₂‐Tyrac) and 3‐(¹⁵N)nitro‐N‐acetyl‐L ‐tyrosine (3‐¹⁵NO₂‐Tyrac). The effects are built up in radical pairs [Tyrac ^. , ¹⁵NO ]^F formed by encounters of independently generated radicals Tyrac ^. and ¹⁵NO . Quantitative ¹⁵N‐CIDNP studies show that nitrogen dioxide dependent reactions are the main if not the only pathways for yielding both nitrate and nitrated products.     

Inhibition of peroxynitrite-induced nitration of tyrosine by glutathione in the presence of carbon dioxide through both radical repair and peroxynitrate formation

Peroxynitrite (ONOO-/ONOOH) is assumed to react preferentially with carbon dioxide in vivo to produce nitrogen dioxide (NO2*) and trioxocarbonate(1-) (CO3*-) radicals. We have studied the mechanism by which glutathione (GSH) inhibits the NO2*/CO3*--mediated formation of 3-nitrotyrosine. We found that even low concentrations of GSH strongly inhibit peroxynitrite-dependent tyrosine consumption (IC50 = 660 microM) as well as 3-nitrotyrosine formation (IC50) = 265 microM). From the determination of the level of oxygen produced or consumed under various initial conditions, it is inferred that GSH inhibits peroxynitrite-induced tyrosine consumption by re-reducing (repairing) the intermediate tyrosyl radicals. An additional protective pathway is mediated by the glutathiyl radical (GS*) through reduction of dioxygen to superoxide (O2*-) and reaction with NO2* to form peroxynitrate (O2NOOH/O2NOO-), which is largely unreactive towards tyrosine. Thus, GSH is highly effective in protecting tyrosine against an attack by peroxynitrite in the presence of CO2. Consequently, formation of 3-nitrotyrosine by freely diffusing NO2* radicals is highly unlikely at physiological levels of GSH.     

Generation of peroxynitrite from reaction of N-acetyl-N-nitrosotryptophan with hydrogen peroxide over a wide range of pH values

The novel reaction of N-acetyl-N-nitrosotryptophan (NANT) with hydrogen peroxide to yield peroxynitrite is demonstrated. Quantum chemical calculations performed at CBS-QB3 level of theory predicted that the reaction of N-nitrosoindole with both H(2)O(2) and its corresponding anion is thermodynamically feasible. At pH 13, the formation of peroxynitrite from the bimolecular reaction of NANT with H(2)O(2) is unequivocally demonstrated by (15)N NMR spectrometry. In order to prove the intermediacy of peroxynitrite from the NANT-H(2)O(2) system at neutral (7.4) and acidic pH (4.5), the characteristic pattern of CIDNP (chemically induced dynamic nuclear polarization) signals were recorded, i.e. enhanced absorption in the (15)N NMR signal of nitrate and emission in the (15)N NMR signal of nitrite. Most interestingly, the NANT-H(2)O(2) system nitrated N-acetyltyrosine at pH 4 via recombination of freely diffusing nitrogen dioxide and tyrosyl radicals, but nitration was negligible at pH 7.4. Since the combination between NANT and H(2)O(2) is slow, endogenous N-nitrosotryptophan residues cannot act as a "carrier" for peroxynitrite.     

Aromatic hydrocarbon nitration under tropospheric and combustion conditions. A theoretical mechanistic study

The viability of some nitration pathways is explored for benzene (B), naphthalene (N), and in part pyrene (P). In principle, functionalization can either take place by direct nitration (NO2 or N2O5 attack) or be initiated by more reactive species, as the nitrate and hydroxyl radicals. The direct attack of the NO2 radical on B and N, followed by abstraction of the H geminal to the nitro group (most likely accomplished by 3O2) could yield the final nitro-derivatives. Nevertheless, the initial step (NO2 attack) involves significant free energy barriers. N2O5 proves to be an even worst nitrating agent. These results rule out direct nitration at room temperature. Instead, NO3 and, even more easily, HO can form pi-delocalized nitroxy- or hydroxycyclohexadienyl radicals. A subsequent NO2 attack can produce several regio- and diastereoisomers of nitroxy-nitro or hydroxy-nitro cyclohexadienes. In this respect, the competition between NO2 and O2 is considered: the rate ratios are such to indicate that the NO3 and HO initiated pathways are the major source of nitroarenes. Finally, if the two substituents are 1,2-trans, either a HNO3 or a H2O concerted elimination can give the nitro-derivatives. Whereas HNO3 elimination is feasible, H2O elimination presents, by contrast, a high barrier. Under combustion conditions the NO2 direct nitration pathway is more feasible, but remains a minor channel.     

Atmospheric chemistry of a model biodiesel fuel, CH3C(O)O(CH2)2OC(O)CH3: kinetics, mechanisms, and products of Cl atom and OH radical initiated oxidation in the presence and absence of NOx

Relative rate techniques were used to study the kinetics of the reactions of Cl atoms and OH radicals with ethylene glycol diacetate, CH3C(O)O(CH2)2OC(O)CH3, in 700 Torr of N2/O2 diluent at 296 K. The rate constants measured were k(Cl + CH3C(O)O(CH2)2OC(O)CH3) = (5.7 +/- 1.1) x 10(-12) and k(OH + CH3C(O)O(CH2)2OC(O)CH3) = (2.36 +/- 0.34) x 10(-12) cm3 molecule-1 s-1. Product studies of the Cl atom initiated oxidation of ethylene glycol diacetate in the absence of NO in 700 Torr of O2/N2 diluent at 296 K show the primary products to be CH3C(O)OC(O)CH2OC(O)CH3, CH3C(O)OC(O)H, and CH3C(O)OH. Product studies of the Cl atom initiated oxidation of ethylene glycol diacetate in the presence of NO in 700 Torr of O2/N2 diluent at 296 K show the primary products to be CH3C(O)OC(O)H and CH3C(O)OH. The CH3C(O)OCH2O* radical is formed during the Cl atom initiated oxidation of ethylene glycol diacetate, and two loss mechanisms were identified: reaction with O2 to give CH3C(O)OC(O)H and alpha-ester rearrangement to give CH3C(O)OH and HC(O) radicals. The reaction of CH3C(O)OCH2O2* with NO gives chemically activated CH3C(O)OCH2O* radicals which are more likely to undergo decomposition via the alpha-ester rearrangement than CH3C(O)OCH2O* radicals produced in the peroxy radical self-reaction.     

Theoretical investigation of nitration and nitrosation of dimethylamine by N2O4

Reactive nitrogen oxygen species (RNOS) contribute to the deleterious effects attributed to reacting with biomolecules. The mechanisms of the nitration and nitrosation of dimethylamine (DMA), which is the simplest secondary amine by N2O4, a member of RNOS, have been investigated at the CBS-QB3 level of theory. The nitration and nitrosation proceed via different pathways. The nitration of DMA follows three pathways. The first is the abstraction of the hydrogen atom of the amino group of DMA by the NO2 radical followed by a recombination reaction of the resulting aminyl radical with another NO2 radical. The second is DMA directly reacting with symmetrical O2NNO2 leading to dimethylnitramine via a concerted and a stepwise mechanism. The third is the reaction of DMA with asymmetrical ONONO2. By computation, the main pathway for the formation of dimethylnitramine in the gas phase is by DMA directly reacting with asymmetrical ONONO2. As to the nitrosation, a concerted mechanism for the reaction of DMA with asymmetrical ONONO2 plays a major role in nitrosodimethylamine (NDMA) formation. In addition, the solvent effect on these nitration and nitrosation reactions has been also studied by using the implicit polarizable continuum model. Two major pathways of the formation of dimethylnitramine in water were found, and they are the radical process involving NO2 and the concerted mechanism starting from symmetrical O2NNO2. The result of the nitrosation of DMA in water is consistent with that in the gas phase. Comparison of the energy barriers of each mechanism leads to the conclusion that the nitrosation is more favorable than the nitration in the reaction of DMA with N2O4. This conclusion is in good agreement with the experimental results. The results obtained here will help elucidate the mechanism of the lesions of biomolecules by RNOS.     

Comparative DFT study of the spin trapping of methyl, mercapto, hydroperoxy, superoxide, and nitric oxide radicals by various substituted cyclic nitrones

The thermodynamics of the spin trapping of various cyclic nitrones with biologically relevant radicals such as methyl, mercapto, hydroperoxy, superoxide anion, and nitric oxide was investigated using computational methods. A density functional theory (DFT) approach was employed in this study at the B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level. The order of increasing favorability for Delta G(rxn) (kcal/mol) of the radical reaction with various nitrones, in general, follows a trend similar to their respective experimental reduction potentials as well as their experimental second-order rate constants in aqueous solution: NO (14.57) < O2*- (-7.51) < *O2H (-13.92) < *SH (-16.55) < *CH3 (-32.17) < *OH (-43.66). The same qualitative trend is predicted upon considering the effect of solvation using the polarizable continuum model (PCM): i.e., NO (14.12) < O2*- (9.95) < *O2H (-6.95) < *SH (-13.57) < *CH3 (-32.88) < *OH (-38.91). All radical reactions with these nitrones are exoergic, except for NO (and O2*- in the aqueous phase), which is endoergic, and the free energy of activation (Delta G) for the NO additions ranges from 17.7 to 20.3 kcal/mol. This study also predicts the favorable formation of certain adducts that exhibit intramolecular H-bonding interactions, nucleophilic addition, or H-atom transfer reactions. The spin density on the nitronyl N of the superoxide adducts reveals conformational dependences. The failure of nitrones to trap NO at normal conditions was theoretically rationalized due to the endoergic reaction parameters.     

Remarkable Mechanism of the Reaction between Mixed Phosphonium-Iodonium Ylides and Acetylenes

Reactions of mixed phosphonium-iodonium ylides with nitriles and acetylenes allow for the synthesis of not easily accessible and novel heterocyclic compounds in a simple, one-pot, metal-free system. The results of the mechanistic investigation of the reaction of the phosphonium-iodonium ylides with acetylenes by means of spectrophotometry, EPR and NMR spectroscopy are discussed in this review. This investigation allows to account for unusual regularities of these reactions: induction time, acid catalysis, chemically induced dynamic nuclear polarization effect (CIDNP) observed in several systems, and others. The radical character of the initiation of the reaction as a result of acid catalysis of the ylides decomposition on radicals and the participation of radical intermediates in the formation of all target products have been unambiguously established. The mechanism of generation of radical pairs in CIDNP was suggested, and the role of microheterogeniety of the ylide solutions in methylene chloride was substantiated. On the basis of the study of the reaction mechanism, the conditions for the increase in the yields of new heterocyclic compounds can be optimized.     

苯硝化反应中电子转移反应重组能的计算

提出了重组能的量子化学算法,在用CISD/6-31G基组水平上,得到苯硝化反应中反应物及过渡态的结构.并计算了各自交换电子转移反应以及交叉电子转移反应的重组能,同实验重组能进行了比较.计算用了Gaussian 94程序.从重组能的角度分析了苯硝化反应.结果表明,对于NO2++NO2→NO2+NO2+的自交换电子转移反应,重组能较大,结论为: 在芳烃硝化反应中,存在以NO2+为氧化剂的电子转移步骤的可能性很小,而从动力学的角度上,用NO+作反应的氧化剂更有可能.     

Radical energies and the regiochemistry of addition to heme groups. Methylperoxy and nitrite radical additions to the heme of horseradish peroxidase

The heme of hemoproteins, as exemplified by horseradish peroxidase (HRP), can undergo additions at the meso carbons and/or vinyl groups of the electrophilic or radical species generated in the catalytic oxidation of halides, pseudohalides, carboxylic acids, aryl and alkyl hydrazines, and other substrates. The determinants of the regiospecificity of these reactions, however, are unclear. We report here modification of the heme of HRP by autocatalytically generated, low-energy NO2* and CH3OO* radicals. The NO2* radical adds regioselectively to the 4- over the 2-vinyl group but does not add to the meso positions. Reaction of HRP with tert-BuOOH does not lead to heme modification; however, reaction with the F152M mutant, in which the heme vinyls are more sterically accessible, results in conversion of the heme 2-vinyl into a 1-hydroxy-2-(methylperoxy)ethyl group [-CH(OH)CH2OOCH3]. [18O]-labeling studies indicate that the hydroxyl group in this adduct derives from water and the methylperoxide oxygens from O2. Under anaerobic conditions, methyl radicals formed by fragmentation of the autocatalytically generated tert-BuO* radical add to both the delta-meso carbon and the 2-vinyl group. The regiochemistry of these and the other known additions to the heme indicate that only high-energy radicals (e.g., CH3*) add to the meso carbon. Less energetic radicals, including NO2* and CH3OO*, add to heme vinyl groups if they are small enough but do not add to the meso carbons. Electrophilic species such as HOBr, HOCl, and HOSCN add to vinyl groups but do not react with the meso carbons. This meso- versus vinyl-reactivity paradigm, which appears to be general for autocatalytic additions to heme prosthetic groups, suggests that meso hydroxylation of the heme by heme oxygenase occurs by a controlled radical reaction rather than by electrophilic addition.     

Kinetic and thermodynamic properties of the aminoxyl (NH2O*) radical

The product of one-electron oxidation of (or H-atom abstraction from) hydroxylamine is the H2NO* radical. H2NO* is a weak acid and deprotonates to form HNO-*; the pKa(H2NO*) value is 12.6+/-0.3. Irrespective of the protonation state, the second-order recombination of the aminoxyl radical yields N2 as the sole nitrogen-containing product. The following rate constants were determined: kr(2H2NO*)=1.4x10(8) M-1 s-1, kr(H2NO*+HNO-*)=2.5x10(9) M-1 s-1, and kr(2HNO-*)=4.5x10(8) M-1 s-1. The HNO-* radical reacts with O2 in an electron-transfer reaction to yield nitroxyl (HNO) and superoxide (O2-*), with a rate constant of ke(HNO-*+O2-->HNO+O2-*)=2.2x10(8) M-1 s-1. Both O2 and O2-* seem to react with deprotonated hydroxylamine (H2NO-) to set up an autoxidative chain reaction. However, closer analysis indicates that these reactions might not occur directly but are probably mediated by transition-metal ions, even in the presence of chelators, such as ethylenediamine tetraacetic acid (EDTA) or diethylenetriamine pentaacetic acid (DTPA). The following standard aqueous reduction potentials were derived: E degrees (H2NO*,2H+/H3NOH+)=1.25+/-0.01 V; E degrees (H2NO*,H+/H2NOH)=0.90+/-0.01 V; and E degrees (H2NO*/H2NO-)=0.09+/-0.01 V. In addition, we estimate the following: E degrees (H2NOH+*/H2NOH)=1.3+/-0.1 V, E degrees (HNO, H+/H2NO*)=0.52+/-0.05 V, and E degrees (HNO/HNO-*)=-0.22+/-0.05 V. From the data, we also estimate the gaseous O-H and N-H bond dissociation enthalpy (BDE) values in H2NOH, with BDE(H2NO-H)=75-77 kcal/mol and BDE(H-NHOH)=81-82 kcal/mol. These values are in good agreement with quantum chemical computations.     

Electron transfer between guanosine radical and amino acids in aqueous solution. 1. Reduction of guanosine radical by tyrosine

As a model of chemical DNA repair, the reductive electron transfer from the aromatic amino acid tyrosine to the radical of the purine base guanosine monophosphate (GMP) was studied by time-resolved chemically induced dynamic nuclear polarization (CIDNP). The guanosyl radicals were photochemically generated in the quenching reaction of the triplet excited dye 2,2'-dipyridyl. Depending on the pH of the aqueous solution, four different guanosyl radicals were observed. The identification of the radicals was possible because of the high sensitivity of CIDNP to distinguish them through their ability or disability of participating in the degenerate electron hopping reaction with the diamagnetic molecules of guanosine monophosphate in the ground state. The CIDNP kinetics in this three-component system containing the dye, GMP, and N-acetyl tyrosine is strongly dependent on the efficiency of the electron-transfer reaction from tyrosine to the nucleotide radical. Quantitative analysis of the CIDNP kinetics obtained at different concentrations of the amino acid, together with the comparison with the CIDNP kinetics of the two-component systems (dipyridyl/tyrosine and dipyridyl/GMP) allowed for the determination of the rate constant ke of the reductive electron-transfer reaction for five pairs of reactants, with different protonation states depending on the pH: GH++*/TyrOH (pH 1.3), G+*/TyrOH (pH 2.9), G(-H)*/TyrOH (pH 7.5), G(-H)*/TyrO- (pH 11.3), and G(-2H)-*/TyrO- (pH 13.3). The rate constant ke varies from (7.1 +/- 3.0) x 10(8) M-1 s-1 (pH 1.3, 2.9) to less than 6 x 10(6) M-1 s-1 (pH 13.3).     

Reactions of hydrated electron with various radicals: spin factor in diffusion-controlled reactions

The reactions of hydrated electron (eaq-) with various radicals have been studied in pulse radiolysis experiments. These radicals are hydroxyl radical (*OH), sulfite radical anion (*SO3-), carbonate radical anion (CO3*-), carbon dioxide radical anion (*CO2-), azidyl radical (*N3), dibromine radical anion (Br2*-), diiodine radical anion (I2*-), 2-hydroxy-2-propyl radical (*C(CH3)2OH), 2-hydroxy-2-methyl-1-propyl radical ((*CH2)(CH3)2COH), hydroxycyclohexadienyl radical (*C6H6OH), phenoxyl radical (C6H5O*), p-methylphenoxyl radical (p-(H3C)C6H4O*), p-benzosemiquinone radical anion (p-OC6H4O*-), and phenylthiyl radical (C6H5S*). The kinetics of eaq- was followed in the presence of the counter radicals in transient optical absorption measurements. The rate constants of the eaq- reactions with radicals have been determined over a temperature range of 5-75 degrees C from the kinetic analysis of systems of multiple second-order reactions. The observed high rate constants for all the eaq- + radical reactions have been analyzed with the Smoluchowski equation. This analysis suggests that many of the eaq- + radical reactions are diffusion-controlled with a spin factor of 1/4, while other reactions with *OH, *N3, Br2*-, I2*-, and C6H5S* have spin factors significantly larger than 1/4. Spin dynamics for the eaq-/radical pairs is discussed to explain the different spin factors. The reactions with *OH, *N3, Br2*-, and I2*- have also been found to have apparent activation energies less than that for diffusion control, and it is suggested that the spin factors for these reactions decrease with increasing temperature. Such a decrease in spin factor may reflect a changing competition between spin relaxation/conversion and diffusive escape from the radical pairs.     

One-electron oxidation of acetohydroxamic acid: the intermediacy of nitroxyl and peroxynitrite

The pharmacological effects of hydroxamate derivatives have been attributed not only to metal chelation or enzyme inhibition but also to their ability to serve as nitroxyl (HNO/NO(-)) and nitric oxide (NO) donors. However, the mechanism underlying the formation of these reactive nitrogen species is not clear and requires further elucidation. In the present study, one-electron oxidation of acetohydroxamic acid (aceto-HX) by (?)OH, (?)N(3), (?)NO(2), CO(3)(?-), and O(2)(?-) radicals was investigated using pulse radiolysis. It is demonstrated that only (?)OH, (?)N(3), and CO(3)(?-) radicals attack effectively and selectively the deprotonated form of the hydroxamate moiety, yielding the respective transient nitroxide radical. This nitroxide radical is a weak acid (CH(3)C(O)NHO(?), pK(a) = 9.1), which decays via a pH-dependent second-order reaction, 2k(2CH(3)C(O)NO(?-)) = (5.6 ± 0.4) × 10(7) M(-1) s(-1) (I = 0.002 M), 2k(CH(3)C(O)NO(?-) + CH(3)C(O)NHO(?)) = (8.3 ± 0.5) × 10(8) M(-1) s(-1)), and 2k(2CH(3)C(O)NHO(?)) = (8.7 ± 1.3) × 10(7) M(-1) s(-1). The second-order decomposition of the nitroxide yields transient species, one of which decomposes via a first-order reaction whose rate increases linearly upon increasing [CH(3)C(O)NHO(-)] or [OH(-)]. One-electron oxidation of aceto-HX under anoxia does not give rise to nitrite even after exposure to O(2), indicating that NO is not formed during the decomposition of the nitroxide radical. The presence of oxidants such as Tempol or O(2) during CH(3)C(O)NO(?-) decomposition had no effect on the reaction kinetics. Nevertheless, in the presence of Temopl, which does not react with NO but does with HNO, the formation of the hydroxylamine Tempol-H was observed. In the presence of O(2), about 60% of CH(3)C(O)NO(?-) yields ONOO(-), indicating that 30% NO(-) is formed in this system. It is concluded that under pulse radiolysis conditions, the transient nitroxide radicals derived from one-electron oxidation of aceto-HX decompose bimoleculary via a complex mechanism forming nitroxyl rather than NO.     

Pressure dependence of pentyl nitrate formation from the OH Radical-initiated reaction of n-pentane in the presence of NO

The formation yields of 2- and 3-pentyl nitrate from the reactions of 2- and 3-pentyl peroxy radicals with NO have been measured at room temperature over the pressure range 51-744 Torr of N2 + O2, using the OH radical-initiated reaction of n-pentane to generate the pentyl peroxy radicals. The influence of 2- and 3-pentyl nitrate formation from the reaction of 2- and 3-pentoxy radicals with NO2 was investigated by conducting experiments with the initial CH3ONO (the OH radical precursor) and NO concentrations being varied by a factor of 5-10. From experiments carried out with low initial CH3ONO and NO concentrations, the measured yields of 2-pentyl nitrate and 3-pentyl nitrate, defined as ([pentyl nitrate] formed)/([n-pentane] reacted), each increase with increasing total pressure, from 1.10 +/- 0.09% and 1.11 +/- 0.10%, respectively, at 51 +/- 1 Torr of O2 to 5.48 +/- 0.51% and 4.07 +/- 0.31%, respectively, at 737 +/- 4 Torr of N2 + O2.     

Zur Reaktion von Diphenoxyphosphorylchlorid mit N,N-disubstituierten Harnstoffen – Bildung von phosphorylierten Biuret-Verbindungen

Reaction of Diphenoxyphosphorylchloride with N,N-disubstituted Ureas – Formation of Phosphorylated Biuret Compounds N′,N′-disubstituted N-diphenoxyphosphorylureas, (PhO)₂P(O)? NH? CO? NR¹R² (R¹ = R² = Et, 1 ; n-Pr, 2 ; n-Bu, 3 ; i-Bu, 4 ; R¹ = Me and R² = Ph, 5 ) as well as phosphorylated biuret compounds, (PhO)₂P(O)? NH? CO? NH? CO? NR¹R² are obtained in the reaction of diphenoxyphosphorylchloride with N,N-disubstituted ureas and triethylamine. The biuret derivatives are formed via (PhO)₂P(O)NCO. Their yield rises if the reaction is carried out without amine. The X-ray crystal structure analysis of (PhO)₂P(O)? NH? CO? NH? CO? NPr₂, 8 , shows that dimers exist in the crystal with intermolecular as well as intramolecular hydrogen bonds. The framework formed by atoms P? N1? C1(O4)? N2? C2(O5)? N3(C3)C6 is planar. The existence of a rotation barrier along the bond C2–N3 was detected by NMR spectroscopy.     

Oxidation of alkylarenes by nitrate catalyzed by polyoxophosphomolybdates: synthetic applications and mechanistic insights

Alkylarenes were catalytically and selectively oxidized to the corresponding benzylic acetates and carbonyl products by nitrate salts in acetic acid in the presence of Keggin type molybdenum-based heteropolyacids, H(3+)(x)()PV(x)()Mo(12)(-)(x)()O(40) (x = 0-2). H(5)PV(2)Mo(10)O(40) was especially effective. For methylarenes there was no over-oxidation to the carboxylic acid contrary to what was observed for nitric acid as oxidant. The conversion to the aldehyde/ketone could be increased by the addition of water to the reaction mixture. As evidenced by IR and (15)N NMR spectroscopy, initially the nitrate salt reacted with H(5)PV(2)Mo(10)O(40) to yield a N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] intermediate. In an electron-transfer reaction, the proposed N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] complex reacts with the alkylarene substrate to yield a radical-cation-based donor-acceptor intermediate, N(IV)O(2)[H(4)PV(2)Mo(10)O(40)]-ArCH(2)R(+)(*). Concurrent proton transfer yields an alkylarene radical, ArCHR(*), and NO(2). Alternatively, it is possible that the N(V)O(2)(+)[H(4)PV(2)Mo(10)O(40)] complex abstracts a hydrogen atom from alkylarene substrate to directly yield ArCHR(*) and NO(2). The electron transfer-proton transfer and hydrogen abstraction scenarios are supported by the correlation of the reaction rate with the ionization potential and the bond dissociation energy at the benzylic positions of the alkylarene, respectively, the high kinetic isotope effect determined for substrates deuterated at the benzylic position, and the reaction order in the catalyst. Product selectivity in the oxidation of phenylcyclopropane tends to support the electron transfer-proton transfer pathway. The ArCHR(*) and NO(2) radical species undergo heterocoupling to yield a benzylic nitrite, which undergoes hydrolysis or acetolysis and subsequent reactions to yield benzylic acetates and corresponding aldehydes or ketones as final products.     

Thermolyses of O-phenyl oxime ethers. A new source of iminyl radicals and a new source of aryloxyl radicals

Six O-phenyl ketoxime ethers, RR'C=NOPh 1-6, with RR' = diaryl, dialkyl, and arylalkyl, together with N-phenoxybenzimidic acid phenyl ether, PhO(Ph)C=NOPh, 7, have been shown to thermolyze at moderate temperatures with "clean" N-O bond homolyses to yield iminyl and phenoxyl radicals, RR'C=N(*) and PhO(*). Since 1-6 can be synthesized at room temperature, these compounds provide a new and potentially useful source of iminyls for syntheses. The iminyl from 7 undergoes a competition between beta-scission, to PhCN and PhO(*), and cyclization to an oxazole. Rate constants, 10(6) k/s(-1), at 90 degrees C for 1-6 range from 4.2 (RR' = 9-fluorenyl) to 180 (RR' = 9-bicyclononanyl), and that for 7 is 0.61. The estimated activation enthalpies for N-O bond scission are in satisfactory agreement with the results of DFT calculations of N-O bond dissociation enthalpies, BDEs, and represent the first thermochemical data for any reaction yielding iminyl radicals. The small range in k (N-O homolyses) is consistent with the known sigma structure of these radicals, and the variations in k and N-O BDEs with changes in RR' are rationalized in terms of iminyl radical stabilization by hyperconjugation: RR'C=N(*) <--> R(*)R'C[triple bond]N. Calculated N-H BDEs in the corresponding RR'C=NH are also presented.     

On the mechanism of the ascorbic acid-induced release of nitric oxide from N-nitrosated tryptophan derivatives: scavenging of NO by ascorbyl radicals

During the past years, there has been increasing interest in endogenous nitric oxide storage compounds. Recently, we briefly reported on the ascorbate-dependent release of nitric oxide ((.)NO) from N-nitrosotryptophan derivatives. In the present study, the underlying mechanism of (.)NO release is studied in more detail, primarily utilizing N-acetyl-N-nitrosotryptophan (NANT) as a model compound. The initial rate of the ascorbate-induced release of nitric oxide has been found to correspond to the rate of NANT decay. In this process, N-acetyltryptophan (NAT) is produced almost quantitatively. The final yield of nitrite amounted to around 90 % with respect to the applied amount of NANT. However, the total release of nitric oxide was only 60 %, as determined by using an FNOCT-4(fluorescent nitric oxide cheletropic trap number 4) assay. Besides nitric oxide, a second volatile product, dinitrogen oxide (N(2)O), has been identified by using (15)N NMR spectrometry, strongly indicating the intermediacy of nitroxyl (HNO). The formation of intermediate ascorbyl radical anions during the NANT-ascorbate reaction has been monitored by using ESR spectrometry. Unexpectedly, it was found that the primary oxidized product of vitamin C, dehydroascorbic acid (DHA), efficiently consumes nitric oxide. Since ESR spectrometry further revealed that ascorbyl radical anions are also generated during the spontaneous decay of DHA, the DHA-nitric oxide reaction is related to recombination of (.)NO with the thus formed ascorbyl radical anions. A conclusively established mechanism of the NANT-ascorbate reaction is presented, with O-nitrosoascorbate as a key intermediate, as additionally supported by CBS-QB3 calculations. The present study suggests that vitamin C and its oxidation products can chemically counterbalance endogenous nitric oxide levels.