Effect of added nucleophilic species on the rate of primary amino acid nitrosation

The rate of primary amino acid nitrosation, both with and without the addition of nucleophilic species, has been studied using stopped-flow spectrophotometry. The rate of nitrosation in the presence of strong nucleophilic species such as thiocyanate and thiourea was shown to be much faster than nitrosation without the addition of a nucleophile. Rate constants were determined at 25 degrees C for reaction of the amino acids alanine, glycine, and valine with five common nitrosating agents. For the nitrosating agents nitrosyl chloride, nitrosyl bromide, and dinitrogen trioxide the rate of reaction was observed to approach the predicted encounter-controlled limit. However, for nitrosyl thiocyanate and S-nitrosothiourea nitrosation was found to be reaction-controlled. In the reaction-controlled regime, rate constants were found to increase with increasing electrophilic strength of the nitrosating agent, as measured by the parameter En, with a slope indicative of a product-like transition state. Activation energies were also measured, being around 10-30 kJ mol-1 for encounter-controlled rate constants, and 30-50 kJ mol-1 for reaction-controlled rate constants. Our results are discussed in the context of in vivo amino acid nitrosation, where it is proposed that the rate of nitrosation may be considerably greater than currently thought, due to the presence of nucleophilic species.     

Kinetic studies on the formation ofN-nitroso compounds VII. Nitrosation of morpholine in acetate buffer

The kinetics of the nitrosation of morpholine in acetate buffer have been studied. It was found that in the experimental conditions used the effective nitrosating agent is dinitrogen trioxide, whose formation is promoted by the acetate ion in accordance with the scheme: No reaction between nitrosyl acetate and the a mine was observed, probably owing to the low concentration of the former. The proposed mechanism explains the experimental facts that no catalysis by the buffer is observed in conditions in which the rate controlling step is the reaction of N₂O₃ with the amine, and that the catalytic effect has only been observed when the formation of the nitrosating agent is also rate controlling. Values have been calculated for several equilibrium and kinetic constants involved in the mechanism proposed.     

Phenol Photonitration and Photonitrosation upon Nitrite Photolysis in basic solution

Nitrophenols have been detected in some Antarctic lakes, the water of which is basic and rich in nitrate, nitrite and other nutrients. Nitrate or nitrite photolysis could be a possible reaction to explain the presence of these compounds. This work presents evidence for the formation of 2-nitrophenol (2NP), 4-nitrophenol (4NP) and 4-nitrosophenol (4NOP) upon UV irradiation of phenol and nitrite in aerated basic solutions.

The pH dependence of the 2NP initial formation rate is different from those of 4NP and 4NOP. The dependence of the first mainly reflects the phenol/phenolate equilibrium, with phenol yielding 2NP at a higher rate than phenolate. In the case of 4NOP, the initial formation rate vs pH has a maximum at pH 9.5. The pH dependence of 4NOP formation rate suggests that three pathways are likely to operate: nitrosation of undissociated phenol by N₂O₃, prevailing at pH<8.7, nitrosation of phenolate by N₂O₃, prevailing in the pH interval 8.7–10.8, and reaction between phenoxyl radical and ^?NO, prevailing at pH>10.8. Phenol nitrosation by N₂O₃ is favoured when phenol is negatively charged (phenolate), but it is also disfavoured at alkaline pH values, owing to the depletion of N₂O₃ (the nitrosating agent) by basic hydrolysis. Differently from 2NP, the initial formation rate vs pH of 4NP is very similar to that of 4NOP, suggesting that 4NP may originate from the oxidation of 4NOP. Moreover, while in neutral and acidic solutions the formation rate of 2NP is slightly higher than that of 4NP, in the pH interval 8–12 the formation of 4NP is much more rapid than that of 2NP. This indicates that the pH of natural waters influences the ratio of nitroisomers.     

Structure–activity relationship of nitrosating agents in the nitrosation reactions of ammonia: a theoretical study

Nitrosating agents (NAs) stimulate the formation of powerful mutagenic and carcinogenic N-nitrosamines. As a model reaction, the nitrosation of ammonia by a series of NAs, i.e., HONO, N₂O₃, N₂O₄, ONOOH, ONCl, ONBr, ONSCN, ONOCH₃, ONOC₂H₅, ONNC, ONOCl, and ONOSOCH₃, was investigated at the CBS-QB3 level of theory. A structure–activity relationship of NAs in the nitrosation reactions of ammonia was established. The results indicate that the nitrosating reactivity of NAs (ON–X) has definite relationship with the heterolytic bond dissociation energies of ON–X and H–X, Mulliken charges of N and X atoms as well as number of the atoms in the ring of the transition state. In light of the established structure–reactivity relationship of NAs, ONNC was found to be a potential powerful nitrosating species.     

Voltammetric study of the oxidation of quercetin and catechin in the presence of cyanide ion

The reaction of electrochemically generated o-benzoquinones from oxidation of quercetin and catechin as Michael acceptors with cyanide ion as nucleophile has been studied using cyclic voltammetry. The reaction mechanism is believed to be EC; including oxidation of catechol moiety of these antioxidants followed by Michael addition of cyanide ion. The observed homogeneous rate constants (k _obs) for reactions were estimated by comparing the experimental voltammetric responses with the digitally simulated results based on the proposed mechanism. The effects of pH and nucleophile concentration on voltammetric behavior and the rate constants of chemical reactions were also described.     

Kinetic and mechanistic aspects of the NO oxidation by O2 in aqueous phase

The oxidation kinetics of NO by O₂ in aqueous solution was observed using a stopped flow apparatus. The kinetics follows a third order rate law of the form k · [NO]² · [O₂] in analogy to gas-phase results. The rate constant at 296 K was measured as (6.4 ± 0.8) · 10⁶ M^?2 s^?1 with an activation energy of 2.3 kcal/mol and a preexponential factor of (4.0 ± 0.5) · 10⁸ M^?2 s^?1. The rate constant displays a very slight pH dependence corresponding to less than a factor of three over the range 0 to 12. The system NO/O₂ in aqueous solution is an efficient nitrosating agent which has been tested using phenol as a substrate over the pH range 0 to 12. The rate limiting step leading to formation of 4-nitrosophenol is the formation of the reactive intermediate whose competitive hydrolysis yields HONO or NO₂^?. The absence of NO₃^? in the autoxidation of NO, the exclusive presence of NO₂^? as a product of the nitrosation reaction of phenol, and the kinetic results of the N₃^? trapping experiments point towards N₂O₃ as the reactive intermediate. © 1994 John Wiley & Sons, Inc.     

Estimation of heterogeneous rate constants of reaction of electrochemically generated o‐benzoquinones with various nucleophiles containing thiol group

The reaction of o‐benzoquinone derived by the oxidation of catechols ( 1a–c ) with some nucleophiles containing thiol group ( 2a–f ) has been studied in various conditions, such as pH, nucleophile concentration, and scan rate, using cyclic voltammetry. In various conditions, based on an EC electrochemical mechanism (“E” represents an electron transfer at the electrode surface and “C” represents a homogeneous chemical reaction), the observed homogeneous rate constants (k_obs) were estimated by comparison of the experimental cyclic voltammetric responses with the digital simulated results for each of the nucleophile. The results show that the magnitude of k_obs is dependent on the nature of the substituted group on the catechol ring and nucleophilicity of nucleophile. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 426–431, 2009     

Kinetic and mechanistic study of the reduction of 2,6-dichlorophenol indophenol by dithionites

The reaction of 2,6-dichlorophenolindophenol (DCPI) and dithionites is studied kinetically by applying the stopped-flow technique. Reaction rate constants are given for the pH range 1.30–6.80. The reaction was found to follow first-order kinetics with respect to each of the reactants. For pH 3.97, 5.10 and 6.80, the second-order reaction rate constant was determined by applying four different technique. Mean values of k = 172±5, 200±2 and 276±4 l mol^?1s^?1 are given for pH 3.97, 5.10 and 6.80, respectively. A mechanism is proposed for the reaction, which suggests partial reactions of all possible species of DCPI and dithionites at any pH. An equation for the calculation of k at any pH is derived, which gives k as a function of [H⁺], the partial reaction rate constants and the dissociation constants of DCPI and H₂S₂O₄. Values of reaction rate constants of all possible partial reactions are also presented.     

Electrochemical Oxidation of Catechols in the Presence of Triethyl Phosphite

The mechanism of electrochemical oxidation of catechol and some of its derivatives have been studied in the presence of triethyl phosphite as a nucleophile in aqueous solution. Voltammetric studies indicate that the quinones derived from catechol, and its derivatives, participate in Michael addition reaction with triethyl phosphite. The reaction mechanism consists of electron transfer followed by a chemical reaction which is named as an EC mechanism. The homogeneous rate constants (k_obs) were estimated by comparing the experimental cyclic voltammograms with the digitally simulated voltammograms based on EC mechanism. Also the effects of nucleophile concentration and substituted group of catechols on voltammetric behavior and the rate constants of chemical reactions were examined.     

1,3-dihalo-5,5-dimethylhydantoin/NaNO2 as an efficient heterogeneous system for the N-nitrosation of N,N-dialkylamines under mild conditions

A combination of 1,3-dihalo-5,5-dimethylhydantoin (X = Br, Cl) and sodium nitrite in the presence of wet SiO₂ was used as an effective nitrosating agent for the nitrosation of N,N-dialkyl amines to their corresponding nitroso derivatives under mild and heterogeneous conditions in good to excellent yields.     

Ruthenium(III)-catalysed oxidation of thiocyanate by periodate in aqueous alkaline medium; autocatalysis in catalysis

The oxidation of thiocyanate by periodate has been studied in alkaline media. A micro quantity of Ru^III is sufficient to catalyse the reaction. The active catalytic species and oxidant in the reaction are understood to be [Ru(H₂O)₅OH]²⁺ and IO⁻ ₄. The autocatalysis exhibited by one of the products, cyanate, is attributed to adduct formation between cyanate and periodate. A composite mechanism and rate law are proposed. The reaction constants involved in the mechanism are evaluated. This revised version was published online in June 2006 with corrections to the Cover Date.     

Reactivity of amino acids in nitrosation reactions and its relation to the alkylating potential of their products

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.     

The kinetics of the oxidation of iodide and thiocyanate ions by 12-tungstocobaltate(III)

The rates and mechanism of the reaction of 12-tungstocobaltate(III) anion with thiocyanate and iodide ions have been examined in aqueous acidic solution and constant ionic strength I = 1.00M (LiClO₄). The reactions follow second-order kinetics, i.e. first-order in both the oxidant and the reductant and the rate constants are found to be independent of hydrogen ions in the range [H⁺] = 0.10–1.00M. Outer-sphere mechanism is postulated for the systems based on the relative inertness of the oxidant and linear free energy relations are employed in demonstrating that in the reaction involving thiocyanate ion, the rate determining step is the diffusion apart of the product while the corresponding step in the iodide reaction is the electron transfer. The latter reaction is also catalysed by both bromide and chloride ions and this is rationalised in terms of possible stabilization of atomic iodine as product by these halide ions.     

Estimation of homogeneous rate constants of reaction of electrochemically generated ortho‐benzoquinones with 1,3‐indandione

Electrochemical oxidation of some catechol derivatives has been studied in the presence of 1,3‐indandione as nucleophile in aqueous solution, by means of cyclic voltammetry and controlled‐potential coulometry. The results indicate the participation of electrochemically produced o‐benzoquinones in the Michael reaction with 1,3‐indandione to form the corresponding new catechol derivatives. On the basis of the EC mechanism, the observed homogeneous rate constants (k_obs) of reaction of produced o‐benzoquinones with 3‐indandione were estimated by comparing the experimental cyclic voltammograms with the digitally simulated results. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 605–613, 2007     

Kinetics of the reaction of α-amino acids with phenalene-1,2,3-trione hydrate

The rate of the title reaction was studied as a function of pH of the reaction medium, temperature, basicities and steric environment of amino groups. Kinetic constants were calculated from a linear free-energy equation permits calculation of separate polar and steric parameters associated with the amino acids which influence rates. The mechanism deduced from the study of the pH-rate profile involving the attack of the unprotonated amino group as a basic amine nucleophile at the CO carbon. The activation parameters of the reaction were determined and ΔS^≠ was found to be a linear function of ΔH^≠.     

The nitrosation of Amino Acids

With a view to clarifying analogies and differences between the mechanisms involved in the nitrosation of amino acids and secondary amines, we studied the kinetics of the nitrosation of five imino acids (azetidine-2-carboxylic acid, pyrrolidine-2-carboxylic acid, piperidine-2-carboxylic acid, piperidine-3-carboxylic acid, and piperidine-4-carboxylic acid) and of the ethyl esters of three of them. Reaction kinetics were determined by the initial rate method, by spectrophotometric monitoring of the concentration of nitroso amino acid formed. The presence of the ? COO^? group in the amino acids opens a new mechanistic route for the nitrosation of the secondary amino group: a nitrosyl carboxylate formed initially acts as an internal nitrosating agent, resulting in intramolecular migration of ? N ? O from the carboxylate group to the secondary amino group. The observed order of the α?, β?, and γ-amino acids as regards the ease of N-nitrosation by this route is explained in terms of the relative energies of (a) the equatorial and axial orientations of the C_ring? C_carboxyl bond, and (b) the chair and boat forms of the piperidine ring. © 1994 John Wiley & Sons, Inc.     

An Efficient Method for N-Nitrosation of Secondary Amines Under Mild and Heterogeneous Conditions

A combination of inorganic acidic salts or silica gel supported inorganic acids and sodium nitrite in the presence of wet SiO₂ was used as an effective nitrosating agent for the nitrosation of secondary amines to their corresponding nitroso drivatives under mild and heterogeneous conditions in moderate to excellent yields. Mg(HSO₄)₂ and NaHSO₄ are superior to all the aforementioned reagents in convenience, yield and purity of the isolated nitrosoamines.     

Kinetic study of the nitrosation of N-alkylureas in dioxane-acetic acid mixtures

The rate constants were determined for the nitrosation reactions of the following substrates: Methyl (MU), Ethyl (EU),Propyl (PU)Butyl (BU), and Allylurea (AU). The rate equation found at a constant pH was: v=k[HNO₂] [Urea]. The reactions were carried out in predominantly organic media(dioxane–acetic acid–water) with differing polarities. The proposed reaction mechanism involves the proton transfer from the protonated N-alkyl-N-nitrosourea to the acetate anion. As the polarity of the medium decreased, an approximation of the rate constants of the nitrosation of the different substrates was observed. This approximation can be interpreted as a function of the impediment generated by the R alkyl radical in the rate controlling step. Accordingly, the substrate reactivity will be associated with the ease in which the protonated N-alkyl-N nitrosurea can transfer the proton to the acetate anion. The results achieved in this study are in accordance with there activities observed in the nitrosation of these substrates in aqueous media MU≫(EU≈PU≈BU)>AU. © 1998 John Wiley & Sons, Inc. Int J Chem Kinet 30: 145–150, 1998.     

Molybdatophosphoric Acid/NaNO2 as an Efficient Procedure for the Chemoselective N‐Nitrosation of Secondary Amines

A combination of molybdatophosphoric acid and sodium nitrite in the presence of wet SiO₂ was used as an effective nitrosating agent for the nitrosation of secondary amines under mild and heterogeneous conditions in good to excellent yields. Also, the results of a computational study are investigated in the gas phase for geometry and properties of proposed structures.     

Carbon dioxide in the nitrosation of amine: catalyst or inhibitor?

Nitrosamines are a class of carcinogenic, mutagenic, and teratogenic compounds generally produced from the nitrosation of amine. This paper investigates the mechanism for the formation of nitrosodimethylamine (NDMA) from the nitrosation of dimethylamine (DMA) by four common nitrosating agents (NO(2)(-), ONOO(-), N(2)O(3), and ONCl) in the absence and presence of CO(2) using the DFT method. New insights are provided into the mechanism, emphasizing that the interactions of CO(2) with amine and nitrosating agents are both potentially important in influencing the role of CO(2) (catalyst or inhibitor). The role of CO(2) as catalyst or inhibitor mainly depends on the nitrosating agents involved. That is, CO(2) shows the catalytic effect when the weak nitrosating agent NO(2)(-) or ONOO(-) is involved, whereas it is an inhibitor in the nitrosation induced by the strong nitrosating agent N(2)O(3) or ONCl. To conclude, CO(2) serves as a "double-edged sword" in the nitrosation of amine. The findings will be helpful to expand our understanding of the pathophysiological and environmental significance of CO(2) and to develop efficient methods to prevent the formation of carcinogenic nitrosamines.