Kinetics of ionization of nitromethane and phenylnitromethane by amines and carboxylate ions in Me2SO-water mixtures. Evidence of ammonium ion-nitronate ion hydrogen bonded complex formation in Me2SO-rich solvent mixtures

Bernasconi, Claude F.; Kliner, Dahv A. V.; Mullin, Amy S.; Ni, Jiu Xiang

doi:10.1021/jo00249a040

Cited by 63 publications

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“…Although nitroalkanes possess relatively high carbon acidity (pK a 10.28 for nitromethane (43, 47)), deprotonation rates can be outstandingly slow, with rate constants for proton transfer from nitromethane to OH Ϫ measured at 27.6 M Ϫ1 s Ϫ1 (43,47). In fact, deprotonation has been proposed to control the rate of elimination of other activated alkanes (25).…”

Section: Discussionmentioning

confidence: 99%

“…7) as follows: O-protonation leading to an aci-Nitro RЈCRϭNO 2 H derivative (aci-Nitro ␤-/␦-adducts) and C ␣ / ␥ -protonation leading to nitroalkane/nitroalkene products (tautomers of the former). A protonation preference for the O-site over the C ␣ -site has been shown for phenylnitromethanes both by experiments under acidic and neutral conditions in aqueous solution and methanol (42)(43)(44) and by computational modeling at the B3LYP/ 6-31ϩG(d,p) level in gas phase (42) or mimicking aqueous solution by including two water molecules in the system (45). The latter study also presented a water-assisted mechanism for conversion of aci-Nitro species toward a nitroalkane C ␣ tautomer, more stable by 8.3 kcal/mol (45).…”

Section: Correlations With Thiol Pk a Suggest That The Thiolate Partimentioning

confidence: 95%

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The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid

Turell

Vitturi

Coitiño

et al. 2017

Journal of Biological Chemistry

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Edited by F. Peter GuengerichNitroalkene fatty acids are formed in vivo and exert protective and anti-inflammatory effects via reversible Michael addition to thiol-containing proteins in key signaling pathways. Nitro-conjugated linoleic acid (NO 2 -CLA) is preferentially formed, constitutes the most abundant nitrated fatty acid in humans, and contains two carbons that could potentially react with thiols, modulating signaling actions and levels. In this work, we examined the reactions of NO 2 -CLA with low molecular weight thiols (glutathione, cysteine, homocysteine, cysteinylglycine, and ␤-mercaptoethanol) and human serum albumin. Reactions followed reversible biphasic kinetics, consistent with the presence of two electrophilic centers in NO 2 -CLA located on the ␤-and ␦-carbons with respect to the nitro group. The differential reactivity was confirmed by computational modeling of the electronic structure. The rates (k on and k off ) and equilibrium constants for both reactions were determined for different thiols. LC-UV-Visible and LC-MS analyses showed that the fast reaction corresponds to ␤-adduct formation (the kinetic product), while the slow reaction corresponds to the formation of the ␦-adduct (the thermodynamic product). The pH dependence of the rate constants, the correlation between intrinsic reactivity and thiol pK a , and the absence of deuterium solvent kinetic isotope effects suggested stepwise mechanisms with thiolate attack on NO 2 -CLA as rate-controlling step. Computational modeling supported the mechanism and revealed additional features of the transition states, anionic intermediates, and final neutral products. Importantly, the detection of cysteine-␦-adducts in human urine provided evidence for the biological relevance of this reaction. Finally, human serum albumin was found to bind NO 2 -CLA both non-covalently and to form covalent adducts at Cys-34, suggesting potential modes for systemic distribution. These results provide new insights into the chemical basis of NO 2 -CLA signaling actions.

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Section: Discussionmentioning

confidence: 99%

Section: Correlations With Thiol Pk a Suggest That The Thiolate Partimentioning

confidence: 95%

The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid

Turell

Vitturi

Coitiño

et al. 2017

Journal of Biological Chemistry

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“…The ionization process is multistep, leading from the carbon acid, via a carbanion or carbanion-like structure, to exocyclic nitronate, cyanate or other forms of anions stabilized by resonance provided for the appropriate electron withdrawing groups present in the molecule (21)(22)(23)(24).…”

Section: Resultsmentioning

confidence: 99%

Potentiometric study of equilibrium acidities of some carbon acids in acetonitrile

Stanczyk-Dunaj¹,

Galezowski²,

Jarczewski³

2002

Can. J. Chem.

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The pK a values for 30 C-acids of the type CH·R 1 ·R 2 ·R 3 -where the R 1 , R 2 , and R 3 substituents are H, alkyl, and aryl, and the most common electron withdrawing groups used in studies of proton-transfer reaction -are given herein. The pK a values have been measured potentiometrically in acetonitrile, using a glass electrode. These values were determined in a buffer solution consisting of a C-acid and its tetrabutylammonium salt, at constant ionic strength (0.001 M), at 25°C. The measurements were done under nitrogen, to prevent oxidation of the anion. The influence of water within the sample of the tetrabutylammonium hydroxide base was negligible. The lowest pK a value of 19.1 was found for bis(4-nitrophenyl)cyanomethane, while the largest pK a s that could be measured were limited by the basicity of the hydroxide ion, and did not exceed 28. A satisfactory agreement between spectrophotometric and potentiometric acidities was achieved.

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“…Formation of an acid–base complex in which the proton may be transferred must therefore involve an energetically unfavourable displacement of a hydrogen‐bonded water molecule from the base by the non‐polar HC bond. Comparisons of the behaviour of hydroxide in water and in aprotic dipolar solvents17, 18 suggest that this exchange may cost more than 50 kJ mol −1 . The extent of the energy penalty varies with substitution at the carbon atom, with inductively electron‐withdrawing groups transferring some favourable polarity to the CH bond.…”

Section: Acid–base Chemistry and The Behaviour Of Carbon Acidsmentioning

confidence: 99%

Primary kinetic hydrogen isotope effects in deprotonations of carbon acids

Watt

2010

J of Physical Organic Chem

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The mechanisms of deprotonation of carbon acids are reviewed to emphasise the important kinetic consequences associated with the internal and solvent reorganisation in forming the conjugate base. Some practicalities of measurements of kinetic hydrogen isotope effects are then considered to show how competing reactions, exchange and mechanistic branching might affect these measurements. Finally, isotopic rate ratios (kH/kD) have been collected for non‐enzymic deprotonations of carbon acids for which temperature dependences have also been determined. All examples contain nitro groups. For reactions in hydroxylic solvents, only two examples are found for which kH/kD > 8 at 25 °C (28.8 and 10.7), possibly indicating a tunnelling contribution. In both cases, values of E aD–E aH are larger and values of AH/AD smaller than the range expected (E aD–E aH = 4.54 kJ mol−1 and 0.7 < AH/AD < 1.4) for effects arising from zero‐point energy differences with no tunnelling contributions. For reactions in aprotic solvents, isotope effects are larger (12.1 < kH/kD < 19.6), but again, the largest of these (19.6 and 15.8) are associated with elevated values of E aD–E aH and small values of AH/AD. It is pointed out that behaviour of this type is accommodated by corrections to the semi‐classical model with shallow tunnelling maximised by high symmetrical barriers. No examples have been found in which large effects are associated with large values of AH/AD and small values of E aD–E aH. Comparisons are made with two recently reported enzyme‐catalysed reactions involving deprotonation of nitroalkanes. Copyright © 2010 John Wiley & Sons, Ltd.

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Kinetics of ionization of nitromethane and phenylnitromethane by amines and carboxylate ions in Me2SO-water mixtures. Evidence of ammonium ion-nitronate ion hydrogen bonded complex formation in Me2SO-rich solvent mixtures

Cited by 63 publications

References 0 publications

The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid

The Chemical Basis of Thiol Addition to Nitro-conjugated Linoleic Acid, a Protective Cell-signaling Lipid

Potentiometric study of equilibrium acidities of some carbon acids in acetonitrile

Primary kinetic hydrogen isotope effects in deprotonations of carbon acids

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