Structure and Raman spectrum of clavulanic acid in aqueous solution

The calculation of the vibrational Raman spectrum of enzyme-bound beta-lactamase inhibitors may be of help to understand the mechanisms responsible for bacterial drug resistance. Here, we present a study of the solvation structure and the vibrational properties of clavulanate, an important beta-lactamase inhibitor, in aqueous solution as obtained from full quantum and hybrid empirical/quantum molecular dynamics simulations at ambient conditions. The analysis of the vibrational density of states indicates that hybrid empirical/quantum mechanical simulations are able to properly describe the vibrational levels of clavulanate in solution. In addition, we propose a computationally efficient protocol to calculate the vibrational Raman effect for large solute molecules in water, which is able to faithfully reproduce the experimentally recorded clavulanate Raman spectrum and discloses the possibility to employ hybrid simulations to assign the experimental Raman spectra of inhibitors bound to beta-lactamases.     

(NHC)AuI]-catalyzed formation of conjugated enones and enals: an experimental and computational study

The [(NHC)AuI]-catalyzed (NHC=N-heterocyclic carbene) formation of alpha,beta-unsaturated carbonyl compounds (enones and enals) from propargylic acetates is described. The reactions occur at 60 degrees C in 8 h in the presence of an equimolar mixture of [(NHC)AuCl] and AgSbF6 and produce conjugated enones and enals in high yields. Optimization studies revealed that the reaction is sensitive to the solvent, the NHC, and, to a lesser extent, to the silver salt employed, leading to the use of [(ItBu)AuCl]/AgSbF6 in THF as an efficient catalytic system. This transformation proved to have a broad scope, enabling the stereoselective formation of (E)-enones and -enals with great structural diversity. The effect of substitution at the propargylic and acetylenic positions has been investigated, as well as the effect of aryl substitution on the formation of cinnamyl ketones. The presence or absence of water in the reaction mixture was found to be crucial. From the same phenylpropargyl acetates, anhydrous conditions led to the formation of indene compounds via a tandem [3,3] sigmatropic rearrangement/intramolecular hydroarylation process, whereas simply adding water to the reaction mixture produced enone derivatives cleanly. Several mechanistic hypotheses, including the hydrolysis of an allenol ester intermediate and SN2' addition of water, were examined to gain an insight into this transformation. Mechanistic investigations and computational studies support [(NHC)AuOH], produced in situ from [(NHC)AuSbF6] and H2O, instead of cationic [(NHC)AuSbF6] as the catalytically active species. Based on DFT calculations performed at the B3LYP level of theory, a full catalytic cycle featuring an unprecedented transfer of the OH moiety bound to the gold center to the C[triple chemical bond]C bond leading to the formation of a gold-allenolate is proposed.     

Investigation into the factors affecting accuracy of mass measurements on a time-of-flight mass spectrometer using Design of Experiment

The results of an investigation of the parameters which have the most significant effect on the accuracy of mass measurements on a quadrupole orthogonal acceleration time-of-flight mass spectrometer (q-oaToF) are reported. The influence of eight factors is investigated: ion abundances of reference and analyte compounds, mass difference between analyte and reference compounds, quality of calibration, number of reference acquisitions averaged and TDC (time-to-digital converter) settings (resolution, Np multiplier (number of pushes correction factor), minimum number of points, i.e. minimum acquisition width which defines a peak). To extract the maximum information from as few experiments as possible, a Design of Experiment approach was used. The data will be used as a basis for developing guidance on accurate mass measurement on q-oaToF instruments.     

Reaction of Cl with CD4 excited to the second C-D stretching overtone

The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C-D oscillator, as in the case of |2100>, wherein a small population of ground-state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction.     

A study of the effects of column porosity on gradient separations of proteins

The type of the stationary phase for reversed-phase liquid chromatography significantly affects the sample elution. Hydrodynamic properties, efficiency and gradient elution of proteins were investigated on five commercial C18 columns with wide-pore totally porous particles, with superficially porous layer particles, non-porous particles and a silica-based monolithic bed. The efficiency in the terms of reduced plate height is higher for low-molecular ethylbenzene than for proteins, but depends on the character of the pores in the individual columns tested. The superficially porous Poroshell and the non-porous Micra columns provide the best efficiency for proteins at high mobile phase flow rates, probably because of similar pore architecture in the stationary phase. The Zorbax column with similar pore architecture as the Poroshell active layer, i.e. narrow pore distribution of wider pores shows better efficiency than the packed column with narrow pores and broad pore distribution. The monolithic column shows lower efficiency for proteins at high flow rates, but it performs better than the broad-pore distribution totally porous particulate columns. Different pore architecture affects also the retention and selectivity for proteins on the individual columns. The retention times on all columns can be predicted using the model for reversed-phase gradient elution developed originally for low-molecular compounds. Consideration of the limited pore volume accessible to the biopolymers has negligible effect on the prediction of retention on the columns packed with non-porous or superficially porous particles, but improves the accuracy of the predicted data for the totally porous columns with broad pore distribution.     

A multilevel characteristics method for periodic convection‐dominated diffusion problems

In this article we introduce a multilevel method in space and time for the approximation of a convection‐diffusion equation. The spatial discretization is of pseudo‐spectral Fourier type, while the time discretization relies on the characteristics method. The approximate solution is obtained as the sum of two components that are advanced in time using different time‐steps. In particular, this requires the introduction of two sets of discretized characteristics curves and of two interpolation operators. We investigate the stability of the scheme and derive some error estimates. They indicate that the high‐frequency term can be integrated with a larger time‐step. Numerical experiments illustrate the gain in computing time due to the multilevel strategy. © 2000 John Wiley & Sons, Inc. Numer Methods Partial Differential Eq 16: 107–132, 2000     

A Landscape of Lignocellulosic Biopolymer Transformations into Valuable Molecules by Heterogeneous Catalysis in C’Durable Team at IRCELYON

This review article highlights part of the research activity of the C’Durable team at IRCELYON in the field of sustainable chemistry. This review presents a landscape of the work performed on the valorization of lignocellulosic biopolymers. These studies intend to transform cellulose, hemicellulose and lignin into valuable molecules. The methodology usually consists in evaluating the behavior of the biopolymers in the absence of catalyst under various conditions (solvent, temperature), and then to assess the influence of a catalyst, most often a heterogeneous catalyst, on the reactivity. The most significant results obtained on the upgrading of cellulose and lignin, which have been mainly investigated in the team, will be presented with an opening on studies involving raw lignocellulose.     

Hydrostannylation of phosphaalkenes [1]

Hydrostannylation reactions of the phosphaalkenes 9,11, and 21 with the triorganotin hydrides 1 proceed by different routes. Whereas the trior-ganotin hydrides 1a,b undergo regioselective 1,2-addition to the P/C double bond of the P-aminophosphaalkene 9 to furnish the 2-stannylphosphanes 17a,b, the 1,2-addition products to the P-halophosphaalkenes 11 and 21 can only be postulated as the reactive intermediates 20 and 23, respectively. The reactions of 11 with 1a,b proceed with cleavage of the triorganotin halide via the diphosphene 15 to furnish the cyclophosphanes 18 and 19. On the other hand, the hydrostannylation reactions of the phosphaalkene 21 are not selective, and the 1,3-diphosphetane 22 is isolated as one of the reaction products. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:453–460, 1998     

Isolation and Characterization of Wax Esters in Fennel and Caraway Seed Oils by SPE-GC

A rapid method for the isolation and quantitative determination of wax esters in vegetable oils was developed. For the first time wax esters in oils were separated from the triglyceride matrix by means of solid-phase extraction, which allows rapid sample preparation in parallel and therefore a high sample throughput. The thus obtained wax ester fractions of fennel and caraway seed oils were analyzed by high temperature gas chromatography. GC-MS analyses were carried out using electron impact ionization in order to characterize the wax ester fraction. With respect to the results of the GC-MS analyses different isomers of saturated wax esters with the same carbon number were observed. Additional monounsaturated wax esters with an unsaturated fatty acid moiety were identified.