Comprehensive and quantitative stability study of ascorbic acid using capillary zone electrophoresis with ultraviolet detection and high‐resolution tandem mass spectrometry

Ascorbic acid is a powerful antioxidant compound involved in many biological functions, and a chronic deficiency is at the origin of scurvy disease. A simple, rapid, and cost‐effective capillary electrophoresis method was developed for the separation and simultaneous quantification of ascorbic acid and the major degradation products: dehydroascorbic acid, furfural, and furoic acid. Systematic optimization of the conditions was performed that enabled baseline separation of the compounds in less than 10 min. In addition to simultaneous quantification of ascorbic acid alongside to the degradation products, stability studies demonstrated the possibility using capillary electrophoresis to separate and identify the major degradation products. Thus, high‐resolution tandem mass spectrometry experiments were conducted in order to identify an unknown degradation product separated by capillary electrophoresis and significantly present in degraded samples. Comparison of mass spectrometry data and capillary electrophoresis electropherograms allowed to identify unambiguously trihydroxy‐keto‐valeraldehyde. Finally, capillary electrophoresis was successfully applied to evaluate the composition of different pharmaceutical preparation of ascorbic acid. Results showed the excellent performance of the capillary electrophoresis method due to the separation of excipients from the compounds of interest, which demonstrated the relevance of using an electrophoretic separation in order to perform comprehensive stability studies of ascorbic acid.     

Joint quantum chemical and polarizable molecular mechanics investigation of formate complexes with penta- and hexahydrated Zn2+: Comparison between energetics of model bidentate,monodentate, and through-water Zn2+ binding modes and evaluation of nonadditivity effects

In order to gain an understanding of the energetics of polycoordinated Zn²⁺ binding to the formate anion (the end side chain of the Asp and Glu residues of proteins), we compare three competing binding modes in the presence of five and six water molecules: a, bidentate binding of Zn²⁺ to both formate oxygens; b, monodentate binding of Zn²⁺ to one formate oxygen; and c, through-water binding of Zn²⁺ to formate, in which the cation remains bound to its first-hydration shell waters and interacts with both formate oxygens through three water molecules. We also investigate a complex d, which is similar to c, in which formate is protonated into formic acid and one water molecule is deprotonated. The computations are carried out using the ab initio self-consistent field/MP2 with three basis sets of increasing size density functional theory, semiempirical AM1 and PM3, and the sum of interactions between fragments ab initio computed (SIBFA) molecular mechanics procedures. The summed energies of the isolated molecules making up the complexes disfavor tautomer d compared to a–c. On the other hand, the ab initio computations give the ordering of intermolecular interaction energies as d formic acid tautomer >b monodentate >a bidentate >c through-water. Whereas the first-order energy E₁ favors both inner-shell Zn²⁺ complexes with formate over the outer-shell complex, the polarization and the charge-transfer components of the second-order energy E₂ both favor the outer-shell complex over the inner-shell one, despite the increased separation between the cation and the highly polarizable formate ion. Energy balances including continuum solvation enthalpies produce an equilibration of complexes a–d. The preference favoring the monodentate complex over the bidentate one is consistent with other ab initio results for formate binding by a fully coordinated Zn²⁺ cation and with structural results from X-ray crystallography. The SIBFA results are consistent with the ab initio results, and the computed interaction energy values match the ab initio ones to within 3%. The effects of nonadditivity are analyzed in the ab initio, SIBFA, and semiempirical computations. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1379–1390, 1999     

Intramolecular chelation of Zn2+ by α‐ and β‐mercaptocarboxamides. A parallel ab initio and polarizable molecular mechanics investigation. Assessment of the role of multipole transferability

α‐ and β‐mercaptocarboxamides constitute the Zn²⁺‐ligating entity of several highly potent metalloenzyme inhibitors. We have studied their interaction energies with Zn²⁺ using the polarizable molecular mechanics procedure SIBFA, and compared them to the corresponding ab initio supermolecule ones. Such validations are necessary to subsequently undertake simulations on complexes of Zn²⁺–metalloenzymes with inhibitors. If the distributed multipoles and polarizabilities are those derived for each ligand in its appropriate Zn²⁺‐binding conformation, a close reproduction of the ab initio binding energies is afforded. However, this representation is not tractable upon increasing the size of the ligands and/or to explore a continuum of binding conformations. This makes it necessary to construct the ligands by resorting to a library of constitutive fragments, namely in this case methanethiolate, formamide, and methane covalently connected together. A close reproduction of the ab initio interaction energies is enabled, but only if the ligand–ligand interactions are computed simultaneously with those occurring with Zn²⁺. This representation accounts for the nonadditivity occurring in the Zn²⁺–methanethiolate–formamide complex, and justifies the use of the distributed multipoles on the fragments for the construction of larger and flexible molecules. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1038–1047, 2001     

Utilisation des déplacements chimiques induits par les lanthanides dans l'analyse conformationnelle d'hétérocycles aromatiques β-carbonylés

The preferential conformation of 3-formyl and 3-acetyl furans, thiophenes, pyrroles and some 3-acyl furans are determined by use of simulated lanthanide induced shifts. The ratios of the different rotamers are similar to those obtained by other n.m.r. methods. This result shows that the complexation does not induce any change in the conformational preference, and thus validates the use of the foregoing method for the conformational analysis of heteroaromatic aldehydes and ketones. In the three heterocycles studied, the carbonyl group shows an X? O trans preferential conformation for the aldehydes and a mixed equilibrium in the case of acetyl groups.     

Etude des propriétés magnétiques de la variété monoclinique du monogermaniure de fer

One of the three allotropic varieties of iron monogermanide has been studied. This phase includes three iron sites located, respectively, at the lattice points 4(i), 2(a), and 2(c). Magnetic measurements revealed the existence of two transition points and an antiferromagnetic behavior, not totally compensated.Using the Mössbauer effect the nature of these magnetic transformations was further studied. It was confirmed by X-ray diffraction spectra and dilatometer measurements.The Mössbauer sites were identified with the cristallographic ones; the magnitude of the hyperfiné fields and of the isomer shift are discussed in terms of spd hybridization. Mössbauer spectroscopy reveals further information on the magnetic interaction existing between the three iron sublattices. These conclusions are confirmed by the effects seen when cobalt and nickel are substituted for iron.     

A new and improved synthesis of a potential antitumour 7h-pyrido[4,3-c ]carbazole analog.

The 6-ethyl-10-methoxy-7H-pyrido[4,3-c ]carbazole is synthesized via a novel and convenient method involving the condensation of the 2-lithio-5-methoxyindole with the appropriate alkyl pyridyl ketone. Quaternarization of this compound by means of a rigid bis(ethyl-piperidyl) linking chain leads to a new potential antitumour dimer.     

TTF[Ni(dmit)2]2: Now as Thin Films and Nanowires

Thin films and nanowires of the molecular superconductor TTF[Ni(dmit)₂]₂ (TTF = tetrathiafulvalene, dmit²⁻=2-thioxo-1,3-dithiol-4,5-dithiolato) are obtained by dipping process on stainless-steel and silicon conversion coatings and on a microrough silicon surface. The deposits are characterized by SEM, Raman spectroscopy and conductivity measurements.     

Unexpected formation of new chiral 3-amino-5-alkyl-2,5-dihydro-1H-pyrrolin-2-ones from N-Boc-α-amino esters

We describe a one-pot process involving the DiBAl-H reduction of the ester moiety of N-protected α-amino esters, followed by Horner-Wadsworth-Emmons olefination in the presence of the trimethyl ester phosphonoglycinate carbanion allowing the formation of new chiral 3-amino-5-alkyl-2,5-dihydro-1H pyrrolin-2-one 5. The Z-enoate 4b, which is formed during this reaction, could be converted into the corresponding lactam 5b under UV irradiation with the presence of BuLi.