José A. Manso

Degradation of carbofuran and carbofuran-derivatives in presence of humic substances under basic conditions

The influence of humic aggregates in water solution upon the chemical stability of carbofuran (CF) and the carbofuran-derivatives, 3-hydroxy-carbofuran (HCF) and 3-keto-carbofuran (KCF), has been investigated in basic media. An inhibition upon the basic hydrolysis of 3-hydroxy-carbofuran and 3-keto-carbofuran (≈ 1.7 and ≈ 1.5-fold, respectively) was observed and it was rationalized in terms of the micellar pseudophase model. Nevertheless, non-significant effect upon the carbofuran stability was found in the presence of humic substances. These behaviors have been compared with the corresponding ones in other synthetic colloidal aggregates.

Combination of X-ray crystallography, SAXS and DEER to obtain the structure of the FnIII-3,4 domains of integrin α6β4

The structure of the FnIII-3,4 region of integrin β4 was solved using a hybrid approach that combines crystallographic structures, SAXS, DEER and molecular modelling. The structure helps in understanding how integrin β4 might bind to other hemidesmosomal proteins and mediate signalling.

Degradation of carbofuran derivatives in restricted water environments: Basic hydrolysis in AOT-based microemulsions

The effect of sodium bis(2-ethylhexyl)sulfosuccinate/isooctane/water microemulsions on the stability of 2,2-dimethyl-2,3-dihydro-1-benzofuran-7-yl methylcarbamate (carbofuran, CF), 3-hydroxy-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-hydroxycarbofuran, HCF) and 3-keto-2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate (3-ketocarbofuran, KCF) in basic media has been studied. The presence of these microheterogeneous media implies a large basic hydrolysis of CF and HCF on increasing surfactant concentration and, also, on increasing water content in the microemulsion. The hydrolysis rate constants are approximately 2- and 10-fold higher than those in pure water for HCF and CF, respectively. In contrast, a steep descent in the rate of decomposition for KCF was observed. These behaviours can be ascribed to the presence of CF derivatives both in the hydrophilic phase and in the lipophilic phase, while the hydroxyl ions are only restricted to the water pool of the microemulsion (hydrophilic phase). The kinetic rate constants for the basic hydrolysis in AOT-based microemulsions have been obtained on the basis of a pseudophase model. Taking into account that an important part of soils are colloids, the possibility of the presence of restricted water environments implies that soil composition and its structure will play an important role in the stability of these carbamates. In fact, we observed that the presence of these restricted aqueous media in the environment, in particular in watersheds and in wastewaters, could reduce significantly the half-life of these pesticides (33% and 91% for HCF and CF, respectively).

Sorbate—Nitrite Interactions: Acetonitrile Oxide as an Alkylating Agent

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; epsilon = 1.4 x 10(4) M(-1) cm(-1); lambda = 519 nm); (iii) the NBP alkylation reaction complies with the rate equation, r = d[AD]/dt = k(alk)(ACNO)[ACNO][NBP]-k(hyd)(AD)[AD], 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.

Artificial Intelligence for Electrical Percolation of AOT-based Microemulsions Prediction

Abstract Different Artificial Neural Network architectures have been assayed to predict percolation temperature of AOT/i-C8/H2O microemulsions. A Perceptron Multilayer Artificial Neural Network with five entrance variables (W value of the microemulsions, additive concentration, molecular weight of the additive, atomic radii and ionic radii of the salt components) was used. Best ANN architecture was formed by five input neurons, two middle layers (with eleven and seven neurons respectively) and one output neuron. Root Mean Square Errors (RMSEs) are 0.18°C (R = 0.9994) for the training set and 0.64°C (R = 0.9789) for the prediction set.

Reactivity of the Mutagen 1,4-Dinitro-2-methylpyrrole as an Alkylating Agent

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; epsilon = 1.14 x 10(4) 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-NO(2) bond as well as the effect of this group on aromaticity.

The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape.

Plakins are large multi-domain proteins that interconnect cytoskeletal structures. Plectin is a prototypical plakin that tethers intermediate filaments to membrane-associated complexes. Most plakins contain a plakin domain formed by up to nine spectrin repeats (SR1–SR9) and an SH3 domain. The plakin domains of plectin and other plakins harbor binding sites for junctional proteins. We have combined x-ray crystallography with small angle x-ray scattering (SAXS) to elucidate the structure of the plakin domain of plectin, extending our previous analysis of the SR1 to SR5 region. Two crystal structures of the SR5-SR6 region allowed us to characterize its uniquely wide inter-repeat conformational variability. We also report the crystal structures of the SR7-SR8 region, refined to 1.8 Å, and the SR7–SR9 at lower resolution. The SR7–SR9 region, which is conserved in all other plakin domains, forms a rigid segment stabilized by uniquely extensive inter-repeat contacts mediated by unusually long helices in SR8 and SR9. Using SAXS we show that in solution the SR3–SR6 and SR7–SR9 regions are rod-like segments and that SR3–SR9 of plectin has an extended shape with a small central kink. Other plakins, such as bullous pemphigoid antigen 1 and microtubule and actin cross-linking factor 1, are likely to have similar extended plakin domains. In contrast, desmoplakin has a two-segment structure with a central flexible hinge. The continuous versus segmented structures of the plakin domains of plectin and desmoplakin give insight into how different plakins might respond to tension and transmit mechanical signals.

Influence Prediction of Small Organic Molecules (Ureas and Thioureas) Upon Electrical Percolation of AOT-Based Microemulsions Using Artificial Neural Networks

Abstract In order to predict percolation temperature of AOT-Based microemulsions (AOT/iC8/H2O w/o microemulsions) in the presence of small organic molecules (ureas and thioureas), different Artificial Neural Network architectures (ANN) have been carried out using a Perceptron Multilayer Artificial Neural Network with three entrance variables (W = value of the microemulsion, additive concentration, logP value). Best ANN architecture consists in three input neurons, one middle layer (with two neurons) and one output neuron. Correlation values were R = 0.9251 for the training set and R = 0.9719 for the prediction set.

Reactivity of some products formed by the reaction of sorbic acid with sodium nitrite: decomposition of 1,4-dinitro-2-methylpyrrole and ethylnitrolic acid.

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)NMP[OH-][NMP] with k(dec)NMP (37.5 degrees C) = 42 +/- 1 M(-1) s(-1). (ii) The rate law for the decomposition of ENA is as follows: r = k(dec)ENA[ENA]K(a)/(K(a) + [H+]), with K(a) being the ENA dissociation constant and k(dec)ENA (37.5 degrees C) = (7.11 +/- 0.04) x 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.

Stability study of Iprodione in alkaline media in the presence of humic acids

The influence of humic aggregates in water solution upon the chemical stability of Iprodione has been investigated under basic conditions. Taking into account that an important part of soils are colloids, the possibility of its presence implies that soil composition and its structure will play an important role in the stability of this pesticide. A kinetic model was applied to this system and the kinetic coefficients were obtained. An inhibition upon the alkaline hydrolysis of Iprodione (2-fold) was observed and it was rationalized in terms of the micellar pseudophase model. These results have been compared with the corresponding ones in the same natural colloidal aggregates in the presence of other pesticides.