Because chemical species with DNA-damaging and mutagenic activity are formed in sorbate−nitrite mixtures and because sorbic acid sometimes coexists with nitrite occurring naturally or incorporated as ...a food additive, the study of sorbate−nitrite interactions is important. Here, the alkylating potential of the products resulting from such interactions was investigated. Drawn were the following conclusions: (i) Acetonitrile oxide (ACNO) is the compound responsible for the alkylating capacity of sorbate−nitrite mixtures; (ii) ACNO alkylates 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; ε = 1.4 × 104 M−1 cm−1; λ = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = dAD/dt = k alk ACNOACNONBP − k hyd ADAD, k alk ACNO being the NBP alkylation rate constant for ACNO and k hyd AD the rate constant for the adduct hydrolysis reaction; (iv) the small fraction of ACNO forming the adduct with NBP, as well as the small magnitude of the quotient (k alk ACNO/k hyd ACNO) as compared with those reported for other alkylating agents, such as some lactones and N-alkyl-N-nitrosoureas, reveals the ACNO effective alkylating capacity to be less significant; (v) the low value of the NBP−ACNO adduct life (defined as the total amount of adduct present along the progression of the NBP alkylation per unit of alkylating agent concentration) points to the high instability of this adduct; and (vi) the obtained results are in accordance with the low carcinogenicity of ACNO.
Sorbic acid reacts with nitrite to yield mutagenic products such as 1,4-dinitro-2-methylpyrrole (NMP) and ethylnitrolic acid (ENA). In order to know the stability of these compounds, a kinetic study ...of their decomposition reactions was performed in the 6.0−9.5 pH range. The conclusions drawn are as follows: (i) The decomposition of NMP occurs through a nucleophilic attack by OH− ions, with the rate equation as follows: r = k dec NMPOH−NMP with k dec NMP (37.5 °C) = 42 ± 1 M−1 s−1. (ii) The rate law for the decomposition of ENA is as follows: r = k dec ENAENAK a/(K a + H+), with K a being the ENA dissociation constant and k dec ENA (37.5 °C) = (7.11 ± 0.04) × 10−5 s−1. (iii) The activation energies for NMP and ENA decomposition reactions are, respectively, E a = 94 ± 3 and 94 ± 1 kJ mol−1. (iv) The observed values for the decomposition rate constants of NMP and ENA in the pH range of the stomach lining cells, into which these species can diffuse, are so slow that they could be the slow determining step of the alkylation mechanisms by some of the products resulting from NMP and ENA decomposition. Thus, the current kinetic results are consistent with the low mutagenicity of these species.
The formation of chemical species with DNA-damaging and mutagenic activity for bacterial test systems was detected in sorbic acid-nitrite mixtures. 1,4-Dinitro-2-methylpyrrole (NMP), one the main ...products resulting from the reaction between sorbic acid and nitrite, has mutagenic properties, and here its alkylating capacity was investigated. The conclusions drawn are as follows: (i) In aqueous medium, after the addition of a hydroxide ion and the subsequent loss of nitrite, NMP affords 5-methyl-3-nitro-1H-pyrrol-2-ol. This species is in equilibrium with 5-methyl-3-nitro-1H-pyrrol-2(5H)-one, the effective alkylating agent responsible for the genotoxic capacity of NMP; (ii) 5-methyl-3-nitro-1H-pyrrol-2(5H)-one alkylates 4-(p-nitrobenzyl)pyridine (NBP), a molecule with nucleophilic characteristics similar to those of DNA bases, forming an adduct (AD; ε = 1.14 × 104 M−1 cm−1); (iii) The calculated energy barrier for the alkylation of NBP for NMP and the value of the fraction of alkylating agent forming the adduct are consistent with the observed mutagenicity of NMP; (iv) The reactivity of NMP can be explained in terms of the instability of the N-NO2 bond as well as the effect of this group on aromaticity.
Integrin alpha 6 beta 4 is a major component of hemidesmosomes that mediate the stable anchorage of epithelial cells to the underlying basement membrane. Integrin alpha 6 beta 4 has also been ...implicated in cell proliferation and migration and in carcinoma progression. The third and fourth fibronectin type III domains (FnIII-3,4) of integrin beta 4 mediate binding to the hemidesmosomal proteins BPAG1e and BPAG2, and participate in signalling. Here, it is demonstrated that X-ray crystallography, small-angle X-ray scattering and double electron-electron resonance (DEER) complement each other to solve the structure of the FnIII-3,4 region. The crystal structures of the individual FnIII-3 and FnIII-4 domains were solved and the relative arrangement of the FnIII domains was elucidated by combining DEER with site-directed spin labelling. Multiple structures of the interdomain linker were modelled by Monte Carlo methods complying with DEER constraints, and the final structures were selected against experimental scattering data. FnIII-3,4 has a compact and cambered flat structure with an evolutionary conserved surface that is likely to correspond to a protein-interaction site. Finally, this hybrid method is of general application for the study of other macromolecules and complexes.
•Reliable results for pressure were obtained by using steady RANS-CFD simulations.•We have determined the forces and moments on the cover with accurateness.•A standard k–ε model is integrated to ...investigate the wind effect by FEM.
In this paper, an evaluation of distribution of the air pressure is determined throughout the laterally closed industrial buildings with curved metallic roofs due to the wind effect by the finite element method (FEM). The non-linearity is due to Reynolds-averaged Navier–Stokes (RANS) equations that govern the turbulent flow. The Navier–Stokes equations are non-linear partial differential equations and this non-linearity makes most problems difficult to solve and is part of the cause of turbulence. The RANS equations are time-averaged equations of motion for fluid flow. They are primarily used while dealing with turbulent flows. Turbulence is a highly complex physical phenomenon that is pervasive in flow problems of scientific and engineering concern like this one. In order to solve the RANS equations a two-equation model is used: the standard k–ɛ model. The calculation has been carried out keeping in mind the following assumptions: turbulent flow, an exponential-like wind speed profile with a maximum velocity of 40m/s at 10m reference height, and different heights of the building ranging from 6m to 10m. Finally, the forces and moments are determined on the cover, as well as the distribution of pressures on the same one, comparing the numerical results obtained with the Spanish CTE DB SE-AE, Spanish NBE AE-88 and European standard rules, giving place to the conclusions that are exposed in the study.
Alkylating Potential of Potassium Sorbate Pérez-Prior, M. Teresa; Manso, José A; García-Santos, M. del Pilar ...
Journal of agricultural and food chemistry,
12/2005, Letnik:
53, Številka:
26
Journal Article
Recenzirano
A kinetic study of the alkylating potential of potassium sorbate (S)a food preservative used worldwidein 7:3 water/dioxane medium was performed. The following conclusions were drawn: (i) Potassium ...sorbate shows alkylating activity on the nucleophile 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, (ii) The NBP alkylation reaction complies with the rate equation r = k alkH+SNBP/(K a + H+), K a being the sorbic acid dissociation constant and k alk the rate constant of NBP alkylation by the undissociated acid. In the range of pH 5−6, the alkylation time ranges between 18 days (pH 5.2) and >1 month (pH ≥6). (iii) NBP alkylation occurs through a reaction with ΔH # = 78 kJ mol-1, which is much higher than those of NBP alkylation by stronger alkylating agents. (iv) The absorption coefficient of the sorbate−NBP adduct was determined to be ε = 204 M-1 cm-1 (λ = 580 nm), this value being rationalized in terms of the adduct structure. (v) The results can help to establish suitable expiration times for products preserved with potassium sorbate. Keywords: Potassium sorbate; alkylation; alkylating reactions
Sorbic Acid as an Alkylating Agent Pérez-Prior, M. Teresa; Manso, José A.; del Pilar García-Santos, M. ...
Journal of solution chemistry,
04/2008, Letnik:
37, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
A kinetic study of the alkylating potential of the sorbic acid + NaOH and sorbic acid + KOH systems was performed in 7:3 (volume/volume) water + dioxane solvent mixtures. The following conclusions ...were drawn. First, the sorbic acid + sorbate system shows alkylating activity on the nucleophile 4-(
p
-nitrobenzyl)pyridine (NBP), which is used as a trap for alkylating agents having nucleophilic characteristics similar to DNA bases. Second, the maximum alkylating capacity is observed in the pH = 5.0 to 6.5 range. Third, the alkylation reactions comply with the rate equation
r
=
k
alk
H
+
SNBP/(
K
a
+H
+
), with
K
a
being the dissociation constant of sorbic acid. Fourth, an enthalpy–entropy (Δ
H
#
/Δ
S
#
) compensation effect for activation quantities is observed by comparing NBP alkylation reactions due to sorbic acid + NaOH, sorbic acid + KOH, as well as potassium sorbate + HCl mixtures. Fifth, the results may help to establish suitable expiration times for products preserved with sorbic acid.
The alkylating potential of β-propiolactone (BPL), β-butyrolactone (BBL), γ-butyrolactone, and δ-valerolactone, which can be formed by the in vivo nitrosation of primary amino acids, was investigated ...kinetically. The nucleophile NBP, 4-(p-nitrobenzyl)pyridine, a trap for alkylating agents, was used as an alkylation substrate. The alkylation reactions were performed under mimicked cellular conditions at neutral pH in water/dioxane solvent mixtures. To gain insight into the effect of the hydrolysis of lactones on their alkylating efficiency, alkylation and competing hydrolysis were studied in parallel. Conclusions were drawn as follows: (i) γ-Butyrolactone and δ-valerolactone afford neither appreciable NBP alkylation nor hydrolysis reactions; (ii) the alkylating potential of BPL is 10-fold higher than that of BBL, the reactivity of both being essentially enthalpy-controlled; (iii) a correlation was found between the alkylating potential of lactones and their carcinogenicity; (iv) the hydrolysis of lactones is not sufficiently effective to prevent alkylation; (v) the efficiency of alkylation, expressed as the alkylation rate/hydrolysis rate ratio, decreases strongly with increasing amounts of dioxane in the reaction media; (vi) the absorption coefficients of the NBP−lactone adducts are as follows: εNBP - BPL = 5101 ± 111 M-1 cm-1 (λ = 584 nm) and εNBP - BBL = 462 ± 19 M-1 cm-1 (λ = 586 nm), the pronounced difference between these values being rationalized in terms of the adducts' structure; and (vii) linear correlations exist between the adducts' absorption coefficients and the water/dioxane ratio in the reaction media.
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