Variational transition-state theory study of the dimethyl sulfoxide (DMSO) and OH reaction

The mechanism for the atmospheric oxidation of DMSO has been studied. For the first time, all the possible channels in the DMSO + OH reaction are studied together theoretically, and their corresponding rate constants have been evaluated under the variational transition-state formalism. Three different channels have been characterized: an addition-elimination process to form MSIA (CH3SOOH) and CH3, a H-abstraction pathway to give CH3SOCH2 and H2O, and a nonkinetically relevant S(N)2-type reaction to form methanol and CH3SO. In agreement with previous experimental and theoretical works, the main product in the DMSO + OH reaction turns out to be the MSIA, with a branching ratio at 298.15 K around 97%. The effects of pressure in the global rate constant have also been analyzed.     

Solvent effect on the determination of sulfamethazine by room-temperature photochemically induced fluorescence

Room-temperature photochemically-induced fluorescence (RTPF) was applied to the determination of sulfamethazine (SMT) in methanol, ethanol and 2-propanol. Optimal ultraviolet irradiation times ranged between 2 and 6 min. Linear calibration graphs were obtained over a concentration range of more than one order of magnitude. The relative standard deviations were within the range 1.4-2.2%. Limits of detection were between 40 and 80 ng/ml. The method was evaluated for its applicability to the analysis of SMT in pharmaceutical formulations.     

Multivariate curve resolution modeling of liquid chromatography-mass spectrometry data in a comparative study of the different endogenous metabolites behavior in two tomato cultivars treated with carbofuran pesticide

A metabonomic study based on the application of multivariate curve resolution and alternating least squares (MCR-ALS) to three-way data sets obtained by liquid chromatography coupled to mass spectrometry detection (LC-MS) was carried out for Rambo and Raf tomato cultivars treated with carbofuran pesticide. Samples were picked up during a 21 days period after treatment and analyzed by LC-MS in scan mode, along with the corresponding blank samples. Then, MCR-ALS was applied to the three-way data sets using column wise augmented matrices, and the evolutionary profiles as a function of the time after treatment were estimated for the metabolites present in both cultivars, as well as their corresponding pure spectra estimations. A comparative study using those estimations showed that some of these metabolites followed different behavior for the different cultivars after treatment. Since all treated and untreated Rambo and Raf samples were picked up according to the same sampling protocol and in a similar state of maturation, any difference in the behavior between profiles can be interpreted as an effect due to the presence of pesticide and to the kind of cultivar. Based on this hypothesis, several PLS-DA approaches were tested to check if it would be possible to classify samples by using the metabolites MCR estimations. Results showed that PLS-DA models for classification of treated or non-treated (blank) samples were the best ones obtained (98.44% of correct classifications for the validation set), which supports the stress effects related to carbofuran treatment. In addition, excellent discrimination among the four groups could be attained (89.06% of correct classifications for the validation set).     

The use of a combined portable X ray fluorescence and multivariate statistical methods to assess a validated macroscopic rock samples classification in an ore exploration survey

The combination of “ex situ” portable X ray fluorescence with unsupervised and supervised pattern recognition techniques such as hierarchical cluster analysis, principal components analysis, factor analysis and linear discriminant analysis have been applied to rock samples, in order to validate a “in situ” macroscopic rock samples classification of samples collected in the Boris Angelo mining area (Central Chile), during a drill-hole survey carried out to evaluate the economic potential of this Cu deposit. The analysed elements were Ca, Cu, Fe, K, Mn, Pb, Rb, Sr, Ti and Zn. The statistical treatment of the geological data has been arisen from the application of the Box-Cox transformation used to transform the data set in normal form to minimize the non-normal distribution of the data. From the statistical results obtained it can be concluded that the macroscopic classification applied to the transformed data permits at least, to distinguish quite well in relation to two of the rock classes defined (70.5% correctly classified (p < 0.05)) as well as for four of the five alteration types defined “in situ” (75% of the total samples).     

A computational analysis of the binding mode of closantel as inhibitor of the <Emphasis Type="Italic">Onchocerca volvulus</Emphasis> chitinase: insights on macrofilaricidal drug design

Onchocerciasis is a leading cause of blindness with at least 37 million people infected and more than 120 million people at risk of contracting the disease; most (99%) of this population, threatened by infection, live in Africa. The drug of choice for mass treatment is the microfilaricidal Mectizan^® (ivermectin); it does not kill the adult stages of the parasite at the standard dose which is a single annual dose aimed at disease control. However, multiple treatments a year with ivermectin have effects on adult worms. The discovery of new therapeutic targets and drugs directed towards the killing of the adult parasites are thus urgently needed. The chitinase of filarial nematodes is a new drug target due to its essential function in the metabolism and molting of the parasite. Closantel is a potent and specific inhibitor of chitinase of Onchocerca volvulus (OvCHT1) and other filarial chitinases. However, the binding mode and specificity of closantel towards OvCHT1 remain unknown. In the absence of a crystallographic structure of OvCHT1, we developed a homology model of OvCHT1 using the currently available X-ray structures of human chitinases as templates. Energy minimization and molecular dynamics (MD) simulation of the model led to a high quality of 3D structure of OvCHIT1. A flexible docking study using closantel as the ligand on the binding site of OvCHIT1 and human chitinases was performed and demonstrated the differences in the closantel binding mode between OvCHIT1 and human chitinase. Furthermore, molecular dynamics simulations and free-energy calculation were employed to determine and compare the detailed binding mode of closantel with OvCHT1 and the structure of human chitinase. This comparative study allowed identification of structural features and properties responsible for differences in the computationally predicted closantel binding modes. The homology model and the closantel binding mode reported herein might help guide the rational development of novel drugs against the adult parasite of O. volvulus and such findings could be extrapolated to other filarial neglected diseases.     

Solid-State P and H NMR Investigations of Amorphous and Crystalline Calcium Phosphates Grown Biomimetically From a Mesoporous Bioactive Glass

By exploiting (1)H and (31)P magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy, we explore the proton and orthophosphate environments in biomimetic amorphous calcium phosphate (ACP) and hydroxy-apatite (HA), as grown in vitro at the surface of a 10CaO-85SiO(2)-5P(2)O(5) mesoporous bioactive glass (MBG) in either a simulated body fluid or buffered water. Transmission electron microscopy confirmed the presence of a calcium phosphate layer comprising nanocrystalline HA. Two-dimensional (1)H-(31)P heteronuclear correlation NMR established predominantly (1)H(2)O?(31)PO(4) (3-) and O(1)H?(31)PO(4) (3-) contacts in the amorphous and crystalline component, respectively, of the MBG surface-layer; these two pairs exhibit distinctly different (1)H→(31)P cross-polarization dynamics, revealing a twice as large squared effective (1)H-(31)P dipolar coupling constant in ACP compared with HA. These respective observations are mirrored in synthetic (well-crystalline) HA, and the amorphous calcium orthophosphate (CaP) clusters that are present in the pristine MBG pore walls: besides highlighting very similar local (1)H and (31)P environments in synthetic and biomimetic HA, our findings evidence closely related NMR characteristics, and thereby similar local structures, of the CaP clusters in the pristine MBG relative to biomimetic ACP.     

Ce and La single- and double-substitutional defects in yttrium aluminum garnet: first-principles study

The atomistic structure, energetics, and electronic structure of single-substitutional Ce and La defects and double-substitutional Ce-La defects in Ce,La-codoped yttrium aluminum garnet (YAG) Y(3)Al(5)O(12) have been studied by means of first-principles periodic boundary conditions density functional theory calculations. Single substitution of Y by Ce or by La produces atomistic expansions around the impurities, which are significantly smaller than the ionic radii mismatches and the overall lattice distortions are found to be confined within their second coordination spheres. In double-substitutional defects, the impurities tend to be as close as possible. La-codoping Ce:YAG provokes an anisotropic expansion around Ce defects. The Ce impurity introduces 4f occupied states in the 5.0 eV computed gap of YAG, peaking 0.25 eV above the top of the valence band, and empty 4f, 5d, and 6s states starting at 3.8 eV in the gap and spreading over the conduction band. La-codoping produces very small effects on the electronic structure of Ce:YAG, the most visible one being the decrease in covalent bonding with one of the oxygen atoms, which shifts 0.05 ? away from Ce and gets 0.04 ? closer to La in the most stable Ce-La double-substitutional defect.     

Asymmetric synthesis of (S)-(-)-xylopinine. Use of the sulfinyl group as an ipso director in aromatic SE

Optically pure (S)-(-)-xylopinine 2 was prepared in three steps in 52% overall yield. Thus, condensation of the carbanion derived from (S)-4 with the (S)-(E)-sulfinylimine 5 gave a 2:1 mixture of tetrahydroisoquinolines 6a and 6b, differing only in configuration at sulfur. N-Desulfinylation of this mixture gave the diastereomeric sulfoxides which, without separation, were converted into (S)-(-)-xylopinine (2) with loss of the sulfinyl moieties under Pictet-Spengler conditions. This unprecedented ipso electrophilic substitution of a sulfinyl group may have synthetic implications beyond that described in this work.