Brønsted acidity of ceric ammonium nitrate in anhydrous DMF. The role of salt and solvent in sucrose cleavage

The generation of an unexpected Brønsted acidity in anhydrous DMF at 50 °C was evidenced by NMR measurements during the investigation on the course of sucrose cleavage by ceric ammonium nitrate (CAN). The formation of a nitrooxy derivative of DMF by reaction with CAN is responsible for this acidity. The reactivity of CAN at 50 °C with several solvents was evaluated by voltammetric and potentiometric measurements. The possible release of protons from these reactions, particularly when aqueous solvent mixtures are used, should always be taken into account in the mechanistic interpretation of CAN synthetic applications.     

Highly regioselective N-trans symmetrical diprotection of cyclen

A high yielding N-trans diprotection procedure for cyclen has been developed by using succinimide carbamate derivates of Boc and Cbz and chloroformate protecting groups.     

Structural and vibrational properties of tetraoxaporphyrin dication, the oxygen analogue of porphyrin, and of isoelectronic diprotonated porphyrin

Structural calculations by means of the density functional method have been performed on tetraoxaporphyrin dication and on isoelectronic diprotonated porphyrin as well as on the sulfur and carbon analogues of porphyrin. A detailed study of the stable conformations of these compounds is reported starting with the most symmetrical conformations and lowering the symmetry along the vibrational coordinates with imaginary frequency. The calculated geometries are related to experimental structures available from X-ray diffraction studies. The Raman spectra of tetraoxaporphyrin dication exciting with micro-Raman instrumentation at 785 nm and of diprotonated porphyrin in near-resonance conditions with the Soret band have been measured. The correlation between frequencies calculated with the DF/B3-LYP/cc-pVDZ procedure for porphyrin, diprotonated porphyrin, and tetraoxaporphyrin dication has allowed for making a vibrational assignment for the latter two systems in excellent agreement with experiment using a single frequency scale factor.     

Evaluation of Accuracy of Electrochemical Isoflavonoid Index for the Determination of Total Isoflavones in Soy Samples

The accuracy of a novel electroanalytical route to determine total isoflavones using a secondary standard from Drug Master File (SW/1211/03) as metrological reference with well‐known traceability and its applicability using representative soy samples is demonstrated. Calibration protocols were used i) for choosing a suitable isoflavone standard to determine the total isoflavone content, ii) to evaluate matrix effects and, iii) to evaluate the overall reliability and performance of the method in analytical operations, extraction and analysis. The inherent electroactivity of both, aglycones and glycoside structures and the similar analytical sensitivity exhibited by the prominent soy isoflavones was relevant to determine the total amount with reliability in terms of accuracy (E<10%) and precision (RSDs<7%) in soy samples. In consequence, the introduction of the term isoflavonoid index as the total amount of isoflavones obtained when they are amperometrically monitorized at +1.0 V as a particular case of the electrochemical index concept is proposed.     

K-stabilized high-oxygen-coverage states on Rh(110): a low-pressure pathway to formation of surface oxide

Using scanning tunneling microscopy, low-energy electron diffraction, and X-ray photoelectron spectroscopy, we studied the evolution of the structure and chemical state of a Rh(110) surface, modified by K adlayers and exposed to high O2 doses at elevated temperatures. We find that oxygen coadsorption on the K-covered Rh(110) leads to massive reconstruction of the Rh(110) surface. Stable reconstructed (10 x 2) and (8 x 2) segmented phases with a local coverage of more than two oxygen atoms per surface Rh atom were observed. Formation of surface oxide, which coexists with the (10 x 2) and (8 x 2) segmented adsorption phases, is evidenced at the highest O2 doses. The development of strongly reconstructed adsorption phases with oxide-like stoichiometry and surface oxide under UHV conditions is explained in terms of the stabilization of the (1 x 2) reconstruction and promotion of O2 dissociation by the K adatoms.     

Stereoselective alkylation of chiral 2-imidoylphenols with organolithium reagents: synthesis of enantiopure 2-aminoalkylphenols

In this paper the addition of organolithium reagents to chiral imidoylphenols to prepare enantiopure phenolic Mannich-type bases is described. The experimental data show that this kind of imine is surprisingly reactive toward organolithium reagents, differently from classical imines, and does not need any Lewis acid or base activation. Moreover, interesting results have been obtained with aldimines but more unusually with ketimines. This reaction results in high yields and diastereoselectivities and allows the preparation of aminophenols quaternary at the C-1 carbon atom, which cannot be prepared with the methods available till now. The sense of asymmetric induction has been explained and confirmed in agreement with the results previously obtained by hydride reduction of the same substrates. In some cases this procedure is complementary to the reductive one, allowing the preparation of the diastereomers less abundant in the reduction. The reaction allows the synthesis of one or the other of the two diastereomers, choosing the opportune starting imidoylphenol and the organolithium reagent.     

Rapid mutation detection in complex genes by heteroduplex analysis with capillary array electrophoresis

Mutational analysis of large multiexon genes without prevalent mutations is a laborious undertaking that requires the use of a high-throughput scanning technique. The Human Genome Project has enabled the development of powerful techniques for mutation detection in large multiexon genes. We have transferred heteroduplex analysis (HA) by conformation-sensitive gel electrophoresis of the two major breast cancer (BC) predisposing genes, BRCA1 and BRCA2, to a multicapillary DNA sequencer in order to increase the throughput of this technique. This new method that we have called heteroduplex analysis by capillary array electrophoresis (HA-CAE) is based on the use of multiplex-polymerase chain reaction (PCR), different fluorescent labels and HA in a 16-capillary DNA sequencer. To date, a total of 114 different DNA sequence variants (19 insertions/deletions and 95 single-nucleotide substitutions - SNS) of BRCA1 and BRCA2 from 431 unrelated BC families have been successfully detected by HA-CAE. In addition, we have optimized the multiplex-PCR conditions for the colorectal cancer genes MLH1 and MSH2 in order to analyze them by HA-CAE. Both genes have been amplified in 13 multiplex groups, which contain the 35 exons, and their corresponding flanking intronic sequences. MLH1 and MSH2 have been analyzed in nine hereditary nonpolyposis colorectal cancer patients, and we have found six different DNA changes: one complex deletion/insertion mutation in MLH1 exon 19 and another five SNS. Only the complex mutation and one SNS may be classified as cancer-prone mutations. Our experience has revealed that HA-CAE is a simple, fast, reproducible and sensitive method to scan the sequences of complex genes.     

Validated procedure for simultaneous trace level determination of the anti-cancer agent gemcitabine and its metabolite in human urine by high-performance liquid chromatography with tandem mass spectrometry

A sensitive, accurate and reproducible procedure has been developed for the quantitative determination of gemcitabine (2',2'-difluorodeoxycytidine, dFdC) and its metabolite 2',2'-difluorodeoxyuridine (2dFdU) in human urine. The samples (2 mL) were extracted by solid-phase extraction (SPE) and analyzed by reversed-phase high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS), operating in multiple reaction monitoring (MRM mode). This procedure was validated using 2'-deoxycytidine as internal standard (IS). The urine assay was linear over the range 0-50 microg/L, with a limit of quantification (LLOQ) of 0.2 microg/L for gemcitabine and 1.0 microg/L for the metabolite. The respective limits of detection (LODs) for dFdC and 2dFdU were 0.05 and 0.3 microg/L. The precision and accuracy of the assay were determined on three different days. The within-series precision was found to be always less than 8.5 and 12.7% for gemcitabine and 2dFdU, respectively. The overall precision expressed as relative standard deviation (CVr) was always less than 7.1% for both analytes. The recovery of gemcitabine was always greater than 90% with a CVr <6.3%. The measurement uncertainty determined from the validation data assessed the possibility of determining this drug and its metabolite at trace levels in urine, considering that the combined uncertainty of the whole procedure was always less than 30%.     

Palladium(II) chloride catalyzes the cross-coupling reaction of 2,5-bis-(butyltelluro)-furan and 1-alkynes

Palladium(II) chloride catalyzed the cross-coupling reaction of 2,5-bis-(butyltelluro) furan and terminal alkynes yielding both symmetrically and unsymmetrically substituted 2,5-bis-acetylenic furan derivatives. The methodology represents a general and efficient protocol for carrying out the synthesis of furan derivatives with potential biological activities.