Estudio cinético de la nitrosación de taurina y homotaurina y del potencial alquilante de los productos de reacción

[ES] La taurina (ácido 1,2-aminoetano sulfónico, Tau), presente en alimentos, suplementos alimentarios y en tejidos humanos, y la homotaurina (ácido 1,3-aminopropano sulfónico, HT), presente en algas rojas y utilizada como nutracéutico, son sulfoaminoácidos susceptibles de nitrosación por los nitritos presentes en alimentos en el medio ácido del estómago. El estudio cinético de las nitrosaciones in vitro de Tau y HT ha revelado que el agente nitrosante efectivo es el N2O3. Se ha observado que el mecanismo de nitrosación está controlado por difusión. La velocidad de nitrosación es máxima a pH = 3 en el caso de la taurina y a pH = 3,3 para la homotaurina. Se ha encontrado que la descomposición del ácido nitroso es un factor que debe tomarse en consideración; por ello se han implementado dos métodos para eliminar su interferencia en las reacciones de nitrosación de ambos sulfoaminoácidos. Se ha estudiado la influencia del pH y de la temperatura en ambas nitrosaciones. Los valores de las constantes de velocidad de nitrosación y de los parámetros de activación han sido similares a los de los aminoácidos carboxílicos estudiados previamente. Se ha demostrado la formación de 1,2 etanosultona (ES) (nitrosación de Tau) y 1,3-propano sultona (PS) (nitrosación de HT) que se hidrolizan a ácido isetiónico y ácido 1,3-hidroxipropano sulfónico, respectivamente. Se ha estudiado la capacidad alquilante de ambas sultonas mediante el test de NBP (4-(p-nitro bencil)piridina), observándose que la alquilación transcurre a través de un mecanismo de reacciones consecutivas donde, tanto las sultonas como sus aductos con la NBP se descomponen. El estudio de la influencia de la temperatura en la velocidad de las reacciones de alquilación y de hidrólisis de las sultonas y de los aductos NBP-sultona ha permitido conocer los valores de la capacidad alquilante y vida del aducto. Se ha encontrado que la PS tiene menor capacidad alquilante que la ES, aunque sus aductos con la NBP son más estables. Ello ha permitido discutir el potencial mutágeno/cancerígeno de ambas sultonas

Connecting the chemical and biological reactivity of epoxides

The chemical reactivity of the mutagenic epoxides (EP) propylene oxide (PO), 1,2-epoxybutane (1,2-EB), and cis- and trans-2,3-epoxybutane (cis- and trans-2,3-EB) with 4-(p-nitrobenzyl)pyridine (NBP), a bionucleophile model for S(N)2 alkylating agents with high affinity for the guanine-N7 position, was investigated kinetically. It was found that three reactions are involved simultaneously: the alkylation reaction of NBP by EP, which yields the corresponding NBP-EP adducts through an S(N)2 mechanism, and EP and NBP-EP hydrolysis reactions. PO and 1,2-EB were seen to exhibit a higher alkylating potential than cis- and trans-2,3-EB. From a study of the correlations between the chemical reactivity (kinetic parameters) and the biological effectiveness of oxiranes, the following conclusions can be drawn: (i) the hydrolysis reactions of epoxides must be taken into account to understand their bioactivity. (ii) The fraction (f) of the alkylating oxirane that forms the adduct and the adduct life (AL) permit the potential of epoxides as bioactive molecules to be rationalized even semiquantitatively; and (iii) alkylation of DNA by epoxides and the O-6-/N7-guanine adduct ratio are directly related to their mutagenicity in vitro.Publicad

Aromatic C-nitrosation of a bioactive molecule. Nitrosation of minoxidil

Minoxidil (2,4-diamino-6-(piperidin-1′-yl)pyrimidine N(3)-oxide; CASRN 38304-91-5) is a bioactive molecule with several nitrosatable groups widely used as an antihypertensive and antialopecia agent. Here the nitrosation of minoxidil was investigated. The conclusions drawn are as follows: (i) In the pH = 2.3–5.0 range, the minoxidil molecule undergoes aromatic C-nitrosation by nitrite. The dominant reaction was C-5 nitrosation through a mechanism that appears to consist of an electrophilic attack on the nitrosatable substrate by H2NO2+/NO+, followed by a slow proton transfer; (ii) the reactivity of minoxidil as a C-nitrosatable substrate proved to be 7-fold greater than that of phenol, this being attributed to the preferred para- and ortho-orientations of the two -NH2groups at positions 2 and 4 of the minoxidil molecule, which activate electrophilic substitution in the C-5 position through their mesomeric effect. The N-nitrosominoxidil resulting from the nitrosation could be potentially harmful to the minoxidil users

Mutagenic products are promoted in the nitrosation of tyramine

Tyramine is a biogenic compound derived from the decarboxylation of the amino acid tyrosine, and is therefore present at important concentrations in a broad range of raw and fermented foods. Owing to its chemical properties, tyramine can react with nitrite, a common food additive, in the acidic medium of stomach to form N- and C-nitroso compounds. Since toxicology studies have shown that the product of C-nitrosation of tyramine is mutagenic, in the present article tyramine nitrosation mechanisms have been characterized in order to discern which of them are favoured under conditions similar to those in the human stomach lumen. To determine the kinetic course of nitrosation reactions, a systematic study of the nitrosation of ethylbenzene, phenethylamine, and tyramine was carried out, using UV–visible absorption spectroscopy. The results show that, under conditions mimicking those of the stomach lumen, the most favoured reaction in tyramine is C-nitrosation, which generates mutagenic products

Alkylating potential of styrene oxide: reactions and factors involved in the alkylation process

The chemical reactivity of styrene-7,8-oxide (SO), an alkylating agent with high affinity for the guanine-N7 position and a probable carcinogen for humans, with 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, was investigated kinetically in water/dioxane media. UV-vis spectrophotometry and ultrafast liquid chromatography were used to monitor the reactions involved...Thanks are given to the Spanish Ministerio de Economía y Competitividad and the European Regional Development Fund (Project CTQ2010-18999) for supporting the research reported in this article. M.G.-P. and J.A.-V. thank the Junta de Castilla y León-FEDER Funds for Ph.D. grants, and R.G.-B. thanks the Spanish Ministerio de Educación for a Ph.D. fellowship.Publicad

Taurine–nitrite interaction as a precursor of alkylation mechanisms

Taurine (2-aminoethanesulphonic acid) is an amino acid-like-compound widely used as an ingredient in some nutraceuticals and energy drinks. Here the interaction of taurine (Tau) with nitrite was investigated. The reactions were carried out mimicking the conditions of the stomach lumen. The conclusions drawn are as follows: (i) Nitrite showed nitrosating capacity on Tau. The rate equation was vN = kobs [Tau] o[nitrite] 2 o, this result suggesting that the yield of nitrosation products in the human stomach would increase sharply with higher nitrate/nitrite intakes; (ii) the experimental results suggest a mechanism for the nitrosation, whose rate-limiting step is bimolecular attack by N2O3; (iii) the nitrosation of taurine affords ethanesultone (ES), which displays alkylating capacity on the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases. Although the NBP alkylation rate for ethanesultone is much higher than those for carcinogenic four-membered ring lactones, resulting in the nitrosation of amino carboxylic acids, the fraction of ES-forming adduct with NBP is much smaller; (iv) in spite of the low risk to human health, since the stomach lumen conditions could be a favourable medium for Tau nitrosation, attention should be paid to potential situations of the concurrence of high contents of taurine and nitrite/nitrate in the diet

The reaction of sodium nitrite with neurotransmitters secreted in the stomach [Dataset]

[EN] Nitroso-compounds are potentially mutagenic and carcinogenic compounds due to their ability to alkylate DNA bases. One of the most common sources of human exposure to nitroso-compounds is their formation in the acidic environment of the stomach by the reaction between electron-rich molecules present in the lumen and sodium nitrite ingested in the diet. To date, the formation of nitroso-compounds by the reaction of nitrite with food components has been investigated in depth, but little attention has been paid to substances secreted in the stomach, such as dopamine or serotonin, whose reaction products with nitrite have proven mutagenic properties. In this article we present a kinetic study with UV-visible spectroscopy of the nitrosation reactions of both molecules, as well as of L-tyrosine, the amino-acid precursor of dopamine. As a result, we have determined their reaction mechanisms, which show that in all of them the favoured reaction product is a stable nitroso-compound and that the molecule whose product is the most mutagenic, serotonin, undergoes two consecutive nitrosation reactions. These findings suggest that more research is needed to understand how this reaction alters the function of these neurotransmitters as well as the potential toxic effects they may have once nitrosated.a) Ministerio de Economía y Competitividad and the European Regional Development Fund. b) Universidad de Salamanca. M.G.J. had got a PhD. grant of the Ministerio de Economía y Competitividad J.A.V. had got a PhD. grant of the Junta de Castilla y León for a PhD. grant.Carpeta 1. Tirosine: 1. Extinction coefficient , 2. Extinction coefficient nitrosotirosine, 3. Reaction orders, 4. Influence Ionic ,Strength, 5. Influence Temperature, 6. Influence pH, 7. KIE. Carpeta 2. Dopamine: 1. Extinction coefficient, 2. Selfoxidation dopamine, 3. Extinction coefficient nitrosodopamine, 4. Catalysis by chloride ions, 5. Reaction orders, 6. Influence Ionic Strength, 7. Influence Temperature, 8. KIE. Carpeta 3. Serotonin: 1. Extinction coefficient, 2. Extinction coefficient nitrosated serotonin, 3. Influence Ionic Strength, 4. Reaction orders, 5. Influence pH, 6. Influence Temperature, 7. KI

Detection of nitrite in water using minoxidil as a reagent

Water analysis is one of the most important issues in environmental chemistry. The increasing scale of water contamination owing to the presence of nitrate and nitrite in the environment has converted it into one of the most serious public health problems in modern society. Here an easy colorimetric method for determining nitrite in water is reported. The method is based on the reaction of nitrite with minoxidil in acidic media, which gives nitrosominoxidil as a product that shows an absorption band in the λ = 315–330 nm range. Minoxidil was the first drug approved by the U.S. Food and Drug Administration as a treatment against alopecia (hair loss), thus leading minoxidil to be one of the most popular and commonly used drugs that can be purchased freely at low cost on the market in the form of topical solutions. The experiment can be completed over 3.5 h, and it can be extended to include a kinetic mechanistic study of the nitrosation reaction. The nitrite detection range makes the method suitable for environmental, food, and physiological analytical applications. By using a brand-name product, student curiosity and interest is kept high throughout the experiment. Finally, questions are provided in the student handout, requiring the students to engage further in topics associated with the context of this practical work

Kinetic study on the reaction of sodium nitrite with neurotransmitters secreted in the stomach

Abstract Nitroso-compounds are potentially mutagenic and carcinogenic compounds due to their ability to alkylate DNA bases. One of the most common sources of human exposure to nitroso-compounds is their formation in the acidic environment of the stomach by the reaction between electron-rich molecules present in the lumen and sodium nitrite ingested in the diet. To date, the formation of nitroso-compounds by the reaction of nitrite with food components has been investigated in depth, but little attention has been paid to substances secreted in the stomach, such as dopamine or serotonin, whose reaction products with nitrite have proven mutagenic properties. In this article, we present a kinetic study with UV–visible spectroscopy of the nitrosation reactions of both molecules, as well as of L-tyrosine, the amino-acid precursor of dopamine. We determined the kinetic parameters and reaction mechanisms for the reactions, studying the influence of the reactants concentration, pH, temperature, and ionic strength on the reaction rate. In all cases, the favoured reaction product was a stable nitroso-compound. Serotonin, the molecule whose product was the most mutagenic, underwent two consecutive nitrosation reactions. These findings suggest that additional biological research is needed to understand how this reaction alters the function of these neurotransmitters as well as the potentially toxic effects they may have once nitrosated