Vitamin C: an experimental and theoretical study on the gas‐phase structure and ion energetics of protonated ascorbic acid

In order to investigate the gas‐phase mechanisms of the acid catalyzed degradation of ascorbic acid (AA) to furan, we undertook a mass spectrometric (ESI/TQ/MS) and theoretical investigation at the B3LYP/6‐31 + G(d,p) level of theory. The gaseous reactant species, the protonated AA, [C₆H₈O₆]H⁺, were generated by electrospray ionization of a 10^?3 M H₂O/CH₃OH (1 : 1) AA solution. In order to structurally characterize the gaseous [C₆H₈O₆]H⁺ ionic reactants, we estimated the proton affinity and the gas‐phase basicity of AA by the extended Cooks's kinetic method and by computational methods at the B3LYP/6‐31 + G(d,p) level of theory. As expected, computational results identify the carbonyl oxygen atom (O2) of AA as the preferred protonation site. From the experimental proton affinity of 875.0 ± 12 kJ mol^?1 and protonation entropy ΔS_p 108.9 ± 2 J mol^?1 K^?1, a gas‐phase basicity value of AA of 842.5 ± 12 kJ mol^?1 at 298 K was obtained, which is in agreement with the value issuing from quantum mechanical computations. Copyright © 2016 John Wiley & Sons, Ltd.     

NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.     

[4+2] Cycloaddition on densely functionalized cyclopentadiene

The Diels-Alder (DA) and hetero-Diels-Alder (HDA) reaction of N-(2,4-dicyano-1,5-dimethyl-3-phenylcyclopenta-2,4-dienyl)-2,2,2-trifluoroacetamide 1 can be conveniently used for the synthesis of biarylic and polycyclic compounds, depending on whether you use alkynes or alkenes as dienophiles. We observe a totally regioselectivity and endo-diastereoselectivity of the cycloaddition reactions.     

Development and in-house validation of a robust and sensitive solid-phase extraction liquid chromatography/tandem mass spectrometry method for the quantitative determination of aflatoxins B1, B2, G1, G2, ochratoxin A, deoxynivalenol, zearalenone, T-2 and HT-2 toxins in cereal-based foods

A sensitive and robust liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous determination of aflatoxins (B(1), B(2), G(1), G(2)), ochratoxin A, deoxynivalenol, zearalenone, T-2 and HT-2 toxins in cereal-based foods. Samples were extracted with a mixture of acetonitrile/water (84:16, v/v) and cleaned up through a polymeric solid-phase extraction column. Detection and quantification of the nine mycotoxins were performed by reversed-phase liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry (LC/ESI-MS/MS), using fully (13)C-isotope-labelled mycotoxins as internal standards. The method was validated in-house for five different cereal processed products, namely barley, oat and durum wheat flours, rye- and wheat-based crisp bread. Recoveries and repeatability of the whole analytical procedure were evaluated at contamination levels encompassing the EU maximum permitted levels for each tested mycotoxin. Recoveries ranged from 89 to 108% for deoxynivalenol, from 73 to 114% for aflatoxins, from 85 to 114% for T-2 and HT-2 toxins, from 64 to 97% for zearalenone, from 74 to 102% for ochratoxin A. Relative standard deviations were less than 16% for all tested mycotoxins and matrices. Limits of detection (signal-to-noise ratio 3:1) ranged from 0.1 to 59.2 μg/kg. The trueness of the results obtained by the proposed method was demonstrated by analysis of reference materials for aflatoxins, deoxynivalenol, zearalenone. The use of inexpensive clean-up cartridges and the increasing availability of less expensive LC/MS/MS instrumentation strengthen the potential of the proposed method for its effective application for reliable routine analysis to assess compliance of tested cereal products with current regulation.     

Time-dependent wave packet study on trans-cis isomerization of HONO

Using a full six-dimensional ab initio potential energy surface and nuclear motion Hamiltonian, time-dependent computations were performed for the cis-trans isomerization of HONO. The multiconfiguration time-dependent Hartree method was used to propagate the six-dimensional wave packets. The initial excitations were chosen to be excitations of the local stretch modes and the HON local bend mode. The energy redistribution within 2 to 5 ps in the energy region of the OH stretching modes in both isomers was analyzed. The Fourier transformed frequency domain spectra were attributed to the eigenstates calculated previously by the time-independent variational approach. The results are also compared with classical trajectory computations of Thomson et al. on empirical surfaces. In agreement with matrix experiments, the cis-->trans isomerization was found to be much faster than the opposite interconversion. The intramolecular dynamics were found to be very complex involving numerous weakly excited delocalized eigenstates and anharmonic resonances. Particularly in the cis-isomer, the excitation of the HON bending local mode leads to fast energy redistribution in cis-trans delocalized modes. Neither the excitation of the OH stretching local mode in the cis nor in the trans form produces a fast isomerization, in agreement with the strongly localized characters of the corresponding eigenstates calculated variationally by Richter et al. and the gas phase spectra of HONO.     

Development and validation of HPLC methods for the analysis of phenethylamine and indoloquinazoline alkaloids in Evodia species

The aim of this study was to evaluate the chromatographic performance of a PEG stationary phase, in comparison with those of C18 columns, for the HPLC analysis of phenethylamine ((+/-)-synephrine) and indoloquinazoline (rutaecarpine and evodiamine) alkaloids in methanolic extracts of fruits of Evodia rutaecarpa (Juss.) Benth. and E. rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang (i.e., E. officinalis Dode) (Rutaceae family). The method was validated and showed good linearity, precision, accuracy, sensitivity, and specificity. The highest content of both phenethylamine and indoloquinazoline alkaloids was found in methanolic fruit extracts of E. rutaecarpa, and it was closely related to the degree of maturity. E. officinalis fruits displayed low amounts of both types of alkaloids. Furthermore, an enantioselective HPLC method for the enantioseparation of (+/-)-synephrine from Evodia fruits was applied, by using a protein-based chiral stationary phase with cellobiohydrolase (CBH) as the chiral selector (Chiral-CBH). Isolation of synephrine from Evodia aqueous fruit extracts was carried out by strong cation-exchange SPE. The results of the application of the method to the analysis of Evodia samples showed that (-)-synephrine was the main component while (+)-synephrine was present in low concentration.     

Rapid quantification of total genomic DNA methylation degree by short-end injection capillary zone electrophoresis

We propose a new capillary zone electrophoresis method applying short-end injection technique for the fast evaluation of methylcystosine/total cytosine ratio after acidic DNA hydrolysis. By short-end injection and by using a 100 mmol/l Tris solution titrated with 1 mol/l phosphoric acid to pH 3.75 as background electrolyte, cytosine and methylcytosine were separated with a good resolution in less than 1.5 min. Stepwise multiple linear regression with DNA methylation degree as the dependent variable and age, cysteine, homocysteine and methionine as independent variables, showed a negative association with age and that total cysteine is the most important determinant of DNA methylation.     

Simulating harmonic oscillator and electrical circuits: a didactical proposal

A Mathematica ^? package is described that uses simulations and animations to illustrate key concepts in harmonic oscillation and electric circuits for students not majoring in physics or mathematics. Students are not required to know the Mathematica^? environment: a user-friendly interface with buttons functionalities and on-line help allows immediate use of the application. Students who are familiar with the programming language have the opportunity to see the set up code that is used, and they can eventually customize it. The goal of the application presented is to enhance student insight, in the spirit of learning by experimentation.     

On the minimum problem for nonconvex, multiple integrals of product type

We consider the problem of minimizing multiple integrals of product type, i.e. where is a bounded, open set in , is a possibly nonconvex, lower semicontinuous function with p-growth at infinity for some and the boundary datum is in (or simply in if ). Assuming that the convex envelope off is affine on each connected component of the set , we prove attainment for () for every continuous, positively bounded below function g such that (i) every point is squeezed between two intervals where g is monotone and (ii) g has no strict local minima. This shows in particular that the class of coefficents g that yield existence to () is dense in the space of continuous, positive functions on . We present examples which show that these conditions for attainment are essentially sharp. Received April 12, 2000 / Accepted May 9, 2000 / Published online November 9, 2000     

[Gd(AAZTA)]− Derivatives with n-Alkyl Acid Side Chains Show Improved Properties for Their Application as MRI Contrast Agents**

Herein, the synthesis and an extensive characterization of two novel Gd(AAZTA) (AAZTA=6-amino-6-methylperhydro-1,4-diazepine tetra acetic acid) derivatives functionalized with short (C₂ and C₄) n-alkyl acid functions are reported. The carboxylate functionality is the site for further conjugations for the design of more specific contrast agents (CAs). Interestingly, it has been found that the synthesized complexes display enhanced properties for use as MRI contrast agents on their own. The stability constants determined by using potentiometric titration and UV/Vis spectrophotometry were slightly higher than the one reported for the parent Gd(AAZTA) complex. This observation might be accounted for by the larger sigma-electron donation of the acyl substituents with respect to the one provided by the methyl group in the parent complex. As far as concerns the kinetic stability, transmetallation experiments with endogenous ions (e.g. Cu²⁺) implied that the Gd³⁺ ions present in these Gd(AAZTA) derivatives show somewhat smaller susceptibility to chemical exchange towards these ions at 25 °C, close to the physiological condition. The ¹H NMR spectra of the complexes with Eu^III and Yb^III displayed a set of signals consistent with half the number of methylene protons present on each ligand. The number of resonances was invariant over a large range of temperatures, suggesting the occurrence of a fast interconversion between structural isomers. The relaxivity values (298 K, 20 MHz) were consistent with q=2 being equal to 8.8 mm ⁻¹ s⁻¹ for the C₂ derivative and 9.4 mm ⁻¹ s⁻¹ for the C₄ one, that is, sensibly larger than the one reported for Gd(AAZTA) (7.1 mm ⁻¹ s⁻¹). Variable-temperature (VT)-T₂ ¹⁷O NMR measurements showed, for both complexes, the presence of two populations of coordinated water molecules, one in fast and one in slow exchange with the bulk water. As the high-resolution ¹H NMR spectra of the analogs with Eu^III and Yb^III did not show the occurrence of distinct isomers (as frequently observed in other macrocyclic lanthanide(III)-containing complexes), we surmised the presence of two fast-interconverting isomers in solution. The analysis of the ¹⁷O NMR VT-T₂ profiles versus temperature allowed their relative molar fraction to be established as 35 % for the isomer with the fast exchanging water and 65 % for the isomer with the water molecules in slower exchange. Finally, ¹H NMRD profiles over an extended range of applied magnetic field strengths have been satisfactory fitted on the basis of the occurrence of the two interconverting species.