Regioselective N-vinylation of cyclic thionocarbamates through a vinyl bis-sulfone methodology

A vinyl bis-sulfone Michael type approach towards heteroatom vinylation was applied on nitrogen derivatives. Cyclic thionocarbamates--mainly 1,3-oxazolidine-2-thiones--were converted into their N-vinyl counterparts; the procedure proved particularly efficient in the case of carbohydrate-derived complex structures.     

Novel 99mTc labeled σ receptor ligand as a potential tumor imaging agent

A novel ^99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA’-^99mTcO) ([ ^99m Tc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA’-ReO)(Re-2) has been prepared and characterized. In vitro competition binding assays show moderate affinity of Re-2 towards σ₁ and σ₂ receptors with K _i values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. injection indicate the accumulation of [ ^99m Tc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [ ^99m Tc]-2 has been inhibited at 20 h after co-injection of [ ^99m Tc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [ ^99m Tc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [ ^99m Tc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [ ^99m Tc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.     

Dynamics studies on thermoresponsive poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) hydrogel in tetrahydrofuran/water mixtures

The properties of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel in tetrahydrofuran/H₂O mixtures were studied. Scanning electron microscopic (SEM) images demonstrate that the hydrogel changes from homogeneous to heterogeneous microstructure upon the addition of tetrahydrofuran to water. This heterogeneous PNIPAAm hydrogel in the mixture solvent exhibits a very slow response rate at temperatures above its lower critical solution temperature. The decreased response rate is attributed to the formation of special ternary complexes including the polymer and the two solvents in the tetrahydrofuran/H₂O mixture. Factors controlling the thermoresponse rate are discussed further and several suggestions are provided for designing and developing fast-response PNIPAAm hydrogels in the future.     

Determination of oxaliplatin in human plasma and plasma ultrafiltrate by graphite-furnace atomic-absorption spectrometry

A method for sensitive determination of the anti-cancer agent oxaliplatin in human plasma and human plasma ultrafiltrate (pUF) is presented. The method is based on the quantification of platinum by graphite-furnace atomic-absorption spectrometry, with Zeeman correction and an atomisation temperature of 2,700°C. Sample pretreatment involves dilution of the samples with a solution containing 0.15 mol L^–1 NaCl and 0.20 mol L^–1 HCl in water. Validation was performed in accordance with the most recent FDA guidelines for bioanalytical method validation. All results were within requirements. The validated ranges of quantification were 0.10–400 mol L^–1 for human pUF and 0.50–400 mol L^–1 for plasma. The assay is now successfully used to support pharmacokinetic studies of cancer patients treated with oxaliplatin.     

Unusual reactivity of ortho-carbonylphenylboronic acids with diethanolamine

The reaction of carbonyl-substituted phenylboronic acids with diethanolamine has been investigated. For compounds containing carbonyl groups at the meta or para positions the reaction occurs exclusively at the boronic acid. Different reactivities were observed for ortho-substituted acetyl- and formylphenylboronic acids where the reaction occurred at both the boronic acid and at the carbonyl group. X-ray studies revealed the presence of a polycyclic structure with tetravalent boron and nitrogen atoms.     

Surface characterization of macroporous glycidyl methacrylate based copolymers by inverse gas chromatography

Two samples of macroporous crosslinked poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate), PGME, with different porosity parameters were synthesized by suspension copolymerization and modified by ring-opening reaction of the pendant epoxy groups with ethylene diamine, EDA. Inverse gas chromatography at infinite dilution was used for the determination of adsorption properties of PGME, and copolymer modified with ethylene diamine, PGME-en. Thermodynamic parameters of adsorption, dispersive components of the surface free energies, and the acid/base constants for the copolymer samples were calculated. The calculated dispersive surface energy values, , for PGME and PGME-en are comparable with the literature data for nonconductive polymers.     

Some investigations on the photostabilization of polypropylene

The effect of substituted hydroxybenzophenone, benzotriazole and organic metal complexes on the photooxidation of PP films has been studied. It has been established that NiDBTC added in 1.0 wt. % is the most effective photostabilizer.While in the case of other stabilizers there is a slight increase in the Co content even during the induction period, with the application of NiDBTC practically no oxidation can be observed before the stabilizer completely disappears. This means that NiDBTC inhibits the photooxidation of the polymer even in low concentration.

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Analytical procedures for quantification of peptides in pharmaceutical research by liquid chromatography–mass spectrometry

Peptide quantification by liquid chromatography–mass spectrometry (LC–MS) combines the high resolving power of reversed-phase (RP) chromatography with the excellent selectivity and sensitivity of mass spectrometric detection. On the basis of comprehensive practical experience in the analysis of small molecules, pharmaceutical research is developing technologies for analysis of a growing number of peptidic drug candidates. This article is a detailed review of procedures based on LC–MS techniques for quantitative determination of peptides. With the focus on pharmaceutical applications several technologies for sample preparation, various aspects of peptide chromatography, important characteristics of ESI–MS, selectivity of MS-detection modes, the large variability of internal standards, and modern instrumentation are discussed. The demand for reliable, robust, sensitive, and accurate methods is discussed using numerous examples from the literature, complemented by experiments and results from our laboratory.     

Effect of silica-type sol-gel carrier’s structure and morphology on a supported Ziegler-Natta catalyst for ethylene polymerization

Silica xerogels with different structures and morphology, synthesized using a sol-gel procedure, were used as a carrier of vanadium catalysts (VOCl₃/AlEt₂Cl) for ethylene polymerization. Two techniques of catalyst synthesis were applied: slurry impregnation and gas-phase adsorption and the relevant polymerization methods were then employed. The effect of the carrier structure and morphology on the vanadium loading in the catalysts, the catalyst’s activity and kinetic stability were investigated.     

Differential response of excision proficient and deficient L5178Y cells to UVC irradiation and benzamide

L5178Y-R and L5178Y-S cells differ in sensitivity to UVC radiation (D0 values: 2.8 and 9.0 J m-2 respectively, exposure in Fischer's medium). The UVC sensitivity is related to the excision repair ability. Benzamide (Bz), an inhibitor of adenosine diphosphoribosyl transferase (ADPRT), does not modify the lethal effect of UVC radiation in L5178Y-R cells, whereas it sensitizes L5178Y-S cells. The content of NAD+ after irradiation decreases only in the latter cells and this decrease can be prevented by 2 mM Bz treatment. In agreement with the survival data, in L5178Y-R cells neither the proportion of abnormal cells nor the frequency of chromatid aberration are affected by 2 mM Bz treatment, in contrast with L5178Y-S cells. Bz slightly reverses inhibition of 3H-thymidine incorporation only in L5178Y-S cells, but it does not affect the proportions of cells in the different phases of the cell cycle in either cell strain after UVC exposure. These data could be taken as an indirect indication of the involvement of ADPRT in DNA repair in UVC-irradiated L5178Y-S cells. However, the increase in the number of DNA strand breaks in UVC-exposed, Bz-treated cells compared with UVC-exposed untreated cells is the same in both L5178Y strains.