Kinetic Studies on the Formation of N-Nitroso Compounds

Nitrosation reactions of amino acids with an -NH(2) group [namely, six alpha-amino acids (glycine, alanine, alpha-aminobutyric acid, alpha-aminoisobutyric acid, valine, and norvaline); two beta-amino acids (beta-alanine and beta-aminobutyric acid), and one gamma-amino acid (gamma-aminobutyric acid)] were studied. Nitrosation was carried out in aqueous acid media, mimicking the conditions of the stomach lumen. The rate equation was r = k(3)(exp)[amino acid][nitrite](2), with a maximum k(3)(exp) value in the 2.3-2.7 pH range. The existence of an isokinetic relationship supports the argument that all the reactions share a common mechanism. A nitrosation mechanism is proposed, and the following conclusions are drawn: (i) Nitrosation reactions of amino acids with a primary amino group in acid media occur with dinitrogen trioxide as the main nitrosating agent. The finding that the nitrosation rate is proportional to the square of the nitrite concentration suggests that the yield of nitrosation products in the stomach would increase sharply with higher nitrate/nitrite intakes. (ii) Stomach hypochlorhydria could be a potential enhancer of in vivo amino acid nitrosation. (iii) The reactivity (k(3)()(exp)) [alpha-amino acids > beta-amino acids > gamma-amino acids] is the same as that found in a previous work for the alkylating potential of lactones formed from nitrosation products of the same amino acids. This implies that the nitrosation reactions of the most common natural amino acids are the most efficient precursors of the most powerful alkylating agents. (iv) The order of magnitude (10(7)-10(8) M(-1) s(-1)) of the bimolecular rate constants of nitrosation shows that such reactions occur through an encounter process.

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“…Since for each pH the value of k 3 exp is experimentally known, α, β, and γ can be calculated by a nonlinear optimization algorithm …”

Section: Resultsmentioning

confidence: 99%

Reactivity of Amino Acids in Nitrosation Reactions and Its Relation to the Alkylating Potential of Their Products

et al. 2002

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“…On the other hand, the results obtained in this work indicate that the rate of formation of the N-nitroso compound for 2-HEP is ≈5 orders of magnitude higher than for piperidine under similar experimental conditions. 26 This quite important difference is due to the presence of an alcoholic group in the molecule, allowing the formation of the corresponding alkyl nitrite, which is responsible for the final internal nitrosation. Therefore, the rate of nitrosation of amines in acid media can be much higher than expected when hydroxy groups are presents in the same molecule.…”

Section: Resultsmentioning

confidence: 99%

Nitrosation of 2-hydroxyethylpiperidine

Magro

Meijide

Provost

et al. 2001

J. Chem. Soc., Perkin Trans. 2

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“…3) has an ordinate at the origin significantly different from zero by Student's t-test, so that both the firstand the second-order terms are recognized. The IRM can therefore be more sensitive to kinetic terms which, though quantitatively small, may qualitatively be very important for deducing a reaction mechanism (3).…”

Section: Advantages Of the Methodsmentioning

confidence: 99%