High-performance liquid chromatographic analysis of vancomycin in plasma, bone, atrial appendage tissue and pericardial fluid

Solid-phase extraction coupled with reversed-phase high-performance liquid chromatography and UV detection was employed for the analysis of the antibiotic vancomycin in patient plasma, bone, atrial appendage, and pericardial fluid. Vancomycin was quantitated in samples from patients undergoing cardiac surgery. Calibrations were linear in the range 3-100 micrograms/ml vancomycin; the lower limit of detection was approximately 3 micrograms/ml in fluids with an absolute limit of detection in bone samples of 0.75 microgram per injection.     

4,6-Thioanhydro-hexopyranosides,synthesis and chemical behaviour of methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-d-gulopyranoside

Methyl 4-0-benzoyl-6-bromo-6-deoxy-α-D-glucopyranoside ($\text{1}$, Figure 1) was converted, via the corresponding ditosylate $\text{2}$, into methyl 2,3-di-0-p-toluenesulfonyl-4-0-benzoyl-6-S-acetyl-6-thio-α-D-glucopyranoside ($\text{3}$) by a selective nucleophilic displacement of 6-bromo-group with thioacetate. Unexpectedly, on treating the compound $\text{3}$ with an excess of sodium methoxide in benzene-methanol (1:1) at room temperature, methyl 2-0-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyranoside ($\text{4}$) was obtained in a yield of 84%. In order to determine the structure of the relatively unstable oily product $\text{4}$, some stable crystalline derivatives ($\text{5}$, $\text{6}$ and $\text{7}$) were prepared. Detailed analysis of the ¹H-NMR-spectra (200 MHz) of $\text{6}$ and $\text{7}$ gave the conclusive evidence for the structure of $\text{4}$ A self-imposing mechanism of the clean and smooth transformation of $\text{3}$ to $\text{4}$ is proposed, involving: a) formation of $\text{9}$ (Figure 2) as a crucial intermediate and b) a highly regioselective epoxide opening in $\text{9}$ (at C-4) by an intramolecular nucleophilic attack of the mercaptide anion from C-6.     

α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine

Despite being relatively benign and not an indicative signature of toxicity, fibril formation and fibrillar structures continue to be key factors in assessing the structure–function relationship in protein aggregation diseases. The inability to capture molecular cross-talk among key players at the tissue level before fibril formation greatly accounts for the missing link toward the development of an efficacious therapeutic intervention for Type II diabetes mellitus (T2DM). We show that human α-calcitonin gene-related peptide (α-CGRP) remodeled amylin fibrillization. Furthermore, while CGRP and/or amylin monomers reduce the secretion of both mouse Ins1 and Ins2 proteins, CGRP oligomers have a reverse effect on Ins1. Genetically reduced Ins2, the orthologous version of human insulin, has been shown to enhance insulin sensitivity and extend the life-span in old female mice. Beyond the mechanistic insights, our data suggest that CGRP regulates insulin secretion and lowers the risk of T2DM. Our result rationalizes how migraine might be protective against T2DM. We envision the new paradigm of CGRP : amylin interactions as a pivotal aspect for T2DM diagnostics and therapeutics. Maintaining a low level of amylin while increasing the level of CGRP could become a viable approach toward T2DM prevention and treatment.

CGRP concentration is elevated in migraine conditions. The protective effect of migraine against type 2 diabetes is attributed to the ability of CGRP to remodel human amylin aggregation and to suppress the secretion of mouse insulin 2 (the orthologue of human insulin).     

Lead hopping using SVM and 3D pharmacophore fingerprints

The combination of 3D pharmacophore fingerprints and the support vector machine classification algorithm has been used to generate robust models that are able to classify compounds as active or inactive in a number of G-protein-coupled receptor assays. The models have been tested against progressively more challenging validation sets where steps are taken to ensure that compounds in the validation set are chemically and structurally distinct from the training set. In the most challenging example, we simulate a lead-hopping experiment by excluding an entire class of compounds (defined by a core substructure) from the training set. The left-out active compounds comprised approximately 40% of the actives. The model trained on the remaining compounds is able to recall 75% of the actives from the "new" lead series while correctly classifying >99% of the 5000 inactives included in the validation set.     

Tentoxin as a scaffold for drug discovery. Total solid-phase synthesis of tentoxin and a library of analogues

[reaction: see text] A solid-phase method for the synthesis of tentoxin has been developed. Two key steps-dehydration and N-alkylation-are carried out while the peptide is anchored to the resin. The method, which has been validated by the preparation of a library of tentoxin analogues, should be applicable to the generation of further libraries that have the tentoxin scaffold structure, as well as other structures containing N-alkylated didehydroamino acids.     

Computer-assisted optimization of selectivity by tuning temperature and carrier gas pressure drop in two GC capillary columns coupled in series

The paper shows a computer-assisted procedure for the optimization of selectivity of two columns coupled in series by tuning the working temperature (using the isothermal mode) and columns coupling-point pressure at constant inlet and outlet carrier gas pressures. The optimization procedure validation was tested by the separation of 32 hydrocarbons in a column series with the aim to resolve the maximum number of components in the shortest possible analysis time.Dedicated to Professor J. F. K. Huber on the occasion of his 65th birthday     

Preliminary Analyses of Radionuclides in Afşin-Elbistan Lignite Samples

This preliminary study describes the concentration of radionuclides ²³⁸U, ²³²Th, ⁴⁰K, and ²²⁶Ra in Afin-Elbistan lignite samples which are primarily used for power generation in the Afin-Elbistan Coal-Fired Power Plant. The results show that the concentration of ²³⁸U is higher in the Afin-Elbistan lignite compared to various world coals whereas the opposite is observed with ²³²Th and ⁴⁰K.     

Analytische Bestimmung von Niob,Tantal, Phosphor,Chlorid und 2,2-Dipyridyl in einigen Komplexverbindungen

Zusammenfassung Die analytische Bestimmung der Metalle, des Dipyridyls und der Chloride in Oxo-chloro-alkoxo-dipyridyl-Komplexverbindungen des Niobs und Tantals wurde beschrieben. Eine modifizierte Methode der Dipyridylanalyse, wie auch der Chloridbestimmung in Gegenwart von Dipyridyl wurde angegeben. Die radiometrische Metallbestimmung in Extraktionsverbindungen von Niob und Tantal mit Di-oktyl-methylenbis-phosphonsäure wurde dargelegt.

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Summary The analytical determination of metals, dipyridyl and chlorides in oxochloro-alkoxo-dipyridyl complex compounds of niobium and tantalum is described. A modified procedure of the dipyridyl analysis and also of the determination of chloride in the presence of dipyridyl is given. The radiometric determination of the metals in extraction compounds of niobium and tantalum with di-octyl-methylene-bis-phosphonic acid is discussed.

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Résumé On décrit le dosage des métaux, du dipyridyle et des chlorures dans les composés complexes oxo, chloro, alcoxo, dipyridyle, du niobium et du tantale. On indique une méthode modifiée pour le dosage de dipyridyle ainsi que pour la détermination des chlorures, en présence de dipyridyle. On décrit le dosage radiométrique des métaux dans les produits d'extraction du niobium et du tantale par l'acide di-octyl-méthylène-bis-phosphonique.

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Vorgetragen beim Symposium für analytische Chemie in Graz, 29. September bis 1. Oktober 1965.     

The Potential Energies of Cohesion of a Crystalline Organic Enantiomer and the Racemate; on the Energy for the Liquid Racemate [1]

The cohesion potential energy of the crystal of one enantiomer of ethyl 3-cyano-3-(3,4-dimethyloxyphenyl)-2,2,4-trimethylpentanoate, −47.7 ± 0.1 kJ mol⁻¹ (0–90°C), was found out from the heat of sublimation (123.2 ± 5.1 kJ mol⁻¹, 78.6°C) and the kinetic energies for the gas phase and the crystal. It was found that the entropy function of Debye’s theory of solids mathematically agreed with the vibrational entropy of the gas (variationally obtained), allowing to disclose the vibrational energy using the Debye energy function (E _vib 835.0 kJ mol⁻¹ (78.6°C), E ⁰ included). E _kin for the crystal (771.1 kJ mol⁻¹ (78.6°C)) was obtained by Debye’s theory with the experimental heat capacity. The cohesion energy represented a moderate part of the sublimation energy. The cohesion energy of the racemic crystal, −44.2 kJ mol⁻¹, was obtained by the heat of formation of the crystal in the solid state (3.0 kJ mol⁻¹, 83.3°C) and E _kin for the crystal (by Debye’s theory). The decrease in cohesion on formation of the crystal accounted for the energy of formation. The change in potential energy on liquefaction of the racemate from the gas state was disclosed obtaining added-up E _{vib + rot} for the liquid in the way as to E _vib for the gas, the Debye entropy function being increasedly suited for the liquid (E _{vib + rot} 763.4 kJ mol⁻¹ (115.4°C)). Positive ΔE _pot, 13.0 kJ mol⁻¹, arised from the increase in electronic energy (Δ _l ν_mean − 154.3 cm⁻¹, by the dielectric nature of the liquid), added to the cohesion energy.     

Synthetic and structural studies on some 1,3-diselena- and 1,3-dithia-[3]ferrocenophanes of germanium and tin. crystal and molecular structure of 1,3-diselena-2,2- dichlorogermyl-[3]ferrocenophane

A series of [3]ferrocenophanes of general formula Fe(C₅H₄X)₂YCl₂ and the spiro compounds [Fe(C₅H₄X)₂]₂Ge (X = S, Se; Y = Ge, Sn) have been prepared by the reaction of ferrocene 1,1′-dithiol and ferrocene 1,1′-diselenol with tetrahalides of germanium and tin. Spectroscopic properties of the compounds are reported. In solution, the compounds are fluxional by a bridge reversal process. The crystal structure of 1,3-diselena-2,2-dichlorogermyl-[3]ferrocenophane at 163 K. has been determined by X-ray diffraction methods. At that temperature, crystals have space group P2₁/n with a 6.222(3), b 16.156(13), c 12.968(4) Å, β 97.53(1)° and Z = 4. Least-squares refinement gave R = 0.033 for 2834 unique significant reflections whose intensities were measured by counter diffractometry. The two SeGe bond lengths are 2.323 and 2.325(1) Å, with GeCl 2.148 and 2.161(1) Å. The SeGeSe bond angle is 118.2(1)°, ClGeCl 104.7(1)°, and SeGeCl angles range from 106.2 to 109.8(1)°. The SeC bond lengths are 1.901 and 1.904(5) Å, with CSeGe angles of 95.8 and 96.5(2)°. The cyclopentadienyl rings are in an eclipsed conformation with a mean twist angle of 2.7°, and are inclined to one another at 6.1°. The Se atoms are displaced from the ring planes by 0.17 and 0.20 Å yielding a non-bonded intramolecular Se…Se contact of 3.99 Å.