Theoretical investigation on 1H and 13C NMR chemical shifts of small alkanes and chloroalkanes

Using density functional theory (DFT) with the B3LYP, PBE, and PBE0 exchange-correlation functionals as well as the Moller-Plesset second-order perturbation theory (MP2) combined with a series of rather extended basis sets, 1H and 13C chemical shifts of small alkanes and chloroalkanes (with different numbers of chlorine atoms on specific positions) have been simulated and compared to experimental data. For the 1H chemical shifts, theory tends to reproduce experiment within the limits of the experimental errors. In the case of 13C chemical shift, the differences between theory and experiment increase monotonically with the number of chlorine atoms and exhibit a deviation from additivity. This behavior is related to the saturation of the experimental 13C chemical shifts with the number of chlorine atoms, whereas the evolution is mostly linear at both DFT and MP2 levels of approximation. This difference has been traced back to the relativistic spin-orbit coupling effects, which are exalted as a result of the enhancement of the s character of the C atom when increasing the number of linked Cl atoms. Thus, it was demonstrated that not only electron correlation but also relativistic effects have to be considered for estimating the 13C chemical shifts when several Cl atoms are directly attached to the C atom. Linear (theory/experiment) regressions have then been performed for the different types of C atoms, i.e., bearing one, two, and three Cl atoms, with excellent correlation coefficients. The linear correlation relationships so obtained can then serve to predict and facilitate the interpretation of the nuclear magnetic resonance spectra of more complex compounds. Furthermore, by investigating the basis set effects, the correlation between the chemical shifts calculated using the 6-311 + G(2d,p) basis set and the more extended 6-311 + G(2df,p) and aug-cc-pvtz basis sets is excellent, demonstrating that the choice of the 6-311 + G(2d,p) basis set for calculating the 1H and 13C chemical shifts is relevant.     

Enhanced mass resolution method development, validation and assay application to support preclinical studies of a new drug candidate

A very highly sensitive and highly selective liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed to evaluate and quantify a new drug candidate in different biological matrices. Following a simple plasma protein precipitation using acetonitrile, the post-treatment samples were analyzed on a C18 column interfaced with a new generation of triple-quadrupole mass spectrometer. The recently introduced triple-quadrupole mass spectrometer, the TSQ Quantum Ultra, with enhanced mass-resolution capability, demonstrated improved sensitivity (0.05 ng/mL), coupled with suitable accuracy and precision, over a broad linear dynamic range (0.05-1000 ng/mL). A comparison of the assay performance data (dynamic range, calibration curve equation, precision and accuracy) of the enhanced resolution method against a unit resolution method under optimized conditions showed the performance improvement of the enhanced mass resolution method for bioanalytical high-throughput applications. The enhanced mass resolution method herein described was successfully applied to the evaluation of the pharmacokinetic profile of a new drug candidate in rat, rabbit and dog plasma samples.     

Side-chain and backbone ordering in a polypeptide

We report results from multicanonical simulations of polyglutamic acid chains of length of ten residues. For this simple polypeptide we observe a decoupling of backbone and side-chain ordering in the folding process. While the details of the two transitions vary between the peptide in gas phase and in an implicit solvent, our results indicate that, independent of the specific surroundings, upon continuously lowering the temperature side-chain ordering occurs only after the backbone topology is completely formed.     

Controlled release from a nanocarrier entrapped within a microcarrier

This study illustrates the entrapment of the dye molecule fluorescein sodium salt (FSS) by hydrogel nanoparticles, which are in turn confined inside a water-in-oil-in-water double-emulsion globule, and its subsequent release by the action of the competing agent hydrochloric acid (HCl). Thus, a "double carrier" concept is being introduced in which a nanoscale delivery vehicle is being transported by a microscale delivery vehicle in order to simultaneously take advantage of both systems. This may facilitate storage and handling while protecting the active substance and improving its action upon application.     

Synthesis of 2-alkenyl-3-(alkoxycarbonyl)furans based on Feist-Benary cyclocondensation of (2,4-dioxobutylidene)phosphoranes with alpha-haloketones and alpha-chloracetaldehyde

3-Acyl-2-alkenylfurans were prepared by "Feist-Benary cyclocondensation" of (2,4-dioxobutylidene)phosphoranes with chloracetaldehyde and alpha-haloketones and subsequent Wittig reactions.     

Structural influences on preferential oxazolone versus diketopiperazine b(2+) ion formation for histidine analogue-containing peptides

Studies of peptide fragment ion structures are important to aid in the accurate kinetic modeling and prediction of peptide fragmentation pathways for a given sequence. Peptide b(2)(+) ion structures have been of recent interest. While previously studied b(2)(+) ions that contain only aliphatic or simple aromatic residues are oxazolone structures, the HA b(2)(+) ion consists of both oxazolone and diketopiperazine structures. The structures of a series of histidine-analogue-containing Xxx-Ala b(2)(+) ions were studied by using action infrared multiphoton dissociation (IRMPD) spectroscopy, fragment ion hydrogen-deuterium exchange (HDX), and density functional theory (DFT) calculations to systematically probe the influence of different side chain structural elements on the resulting b(2)(+) ion structures formed. The b(2)(+) ions studied include His-Ala (HA), methylated histidine analogues, including π-methyl-HA and τ-methyl-HA, pyridylalanine (pa) analogues, including 2-(pa)A, 3-(pa)A, and 4-(pa)A, and linear analogues, including diaminobutanoic acid-Ala (DabA) and Lys-Ala (KA). The location and accessibility of the histidine π-nitrogen, or an amino nitrogen on an aliphatic side chain, were seen to be essential for diketopiperazine formation in addition to the more typical oxazolone structure formation, while blocking or removal of the τ-nitrogen did not change the b(2)(+) ion structures formed. Linear histidine analogues, DabA and KA, formed only diketopiperazine structures, suggesting that a steric interaction in the HisAla case may interfere with the complete trans-cis isomerization of the first amide bond that is necessary for diketopiperazine formation.     

Enzymic Methylation of Ascorbigen and Demethylation of Its N-Methyl Derivative by Pseudomonas savastanoi pv. phaseolicola Bacteria

Biotransformation of ascorbigen and N-methylascorbigen as a model compound pair was studied in the presence of Pseudomonas savastanoi pv. phaseolicola bacterium cells. These compounds were separated from a methanolic mixture by using an overpressured layer chromatographic method. After saturation of the developed chromatoplates with the bacterial cell suspension, the composition of the chromatographic spots was analyzed by means of high performance liquid chromatography. Pattern recognition by independent multicategory analysis was used to compare of the retention behavior of the standard and putative ascorbigen and methylascorbigen, and to manage the analytical data. Results showed that ascorbigen was partially methylated and N-methylascorbigen was partially demethylated by the bacteria. Our new results confirm the former assumption that formaldehyde is formed by demethylation of the N-methyl group of methylascorbigen.

     

On the contact of a spherical membrane enclosing a fluid with rigid parallel planes

The mechanical response of an inflated spherical membrane-fluid structure in contact with rigid parallel planes is studied. The membrane is assumed to be a two-dimensional non-linear elastic and isotropic structure, while no assumption is imposed on the fluid. A numerical procedure is employed to compute the equilibrium configurations of the membrane-fluid structure. This study provides information regarding the contact force, stress distribution and pressure in the membrane and in the enclosed fluid, respectively. It was observed that a transition between unwrinkled to partially wrinkled configurations of the membrane occurs subjected to the loading conditions. Further investigation of the wrinkled configurations is presented.     

Application of Internal Standard for Micro Extraction– Spectrophotometric Determination of Bismuth in Pharmaceutical Formulations

 A micro extraction – spectrophotometric procedure is developed for the determination of bismuth in pharmaceutical formulations. The procedure is based on the extraction of tetraiodobismuthate(III) ion paired with benzyltributylammonium cation into chloroform. The application of Nile Blue as internal standard (IS) enabled good analytical performance for micro-scale analysis. The ratio between the absorbances measured at 491 nm (bismuth complex) and at 632 nm (IS) was taken as the analytical signal. The procedure was carried out in Eppendorf tubes, lowering significantly the use of reagents and the volume of organic solvent. In the calibration range up to 60 mgċl⁻¹, the linear regression coefficient was 0.9999, the CV for 15 mgċl⁻¹ and for 50 mgċl⁻¹ Bi were 1.6% and 0.7% respectively. The results obtained in the analysis of pharmaceutical formulations were in good agreement with the results of EDTA titration method. Received November 25, 1999. Revision February 14, 2000.     

Derived length and products of conjugacy classes

Let G be a supersolvable group and A be a conjugacy class of G. Observe that for some integer η(AA ⁻¹) > 0, AA ⁻¹ = {ab ⁻¹: a, b ∈ A} is the union of η(AA ⁻¹) distinct conjugacy classes of G. Set C _G (A) = {g ∈ G: a ^g = a for all a ∈ A. Then the derived length of G/C _G (A) is less or equal than 2η(AA ⁻¹) − 1.