Iron as a risk factor in neurological diseases

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).     

Infrared study on electrolyte solutions in acetone part III. reactivity of acetone in aldolic condensation

Infrared spectra of perchlorate, halide and nitrate solutions in acetone are studied. The CO and CCC band frequency changes are discussed in terms of the electronic structure of acetone molecules complexed with cation and anion. The correlation between the shift of the CO and CCC bands and the reactivity of acetone molecules in aldolic condensation reaction is given. An explanation of the anion effect in aldolic condensation is proposed.     

An indirect flame emission spectrometry method for the determination of sulphur and sulphur compounds. II

Microchimica Acta - An accurate and simple indirect method of flame-emission spectrometric determination of small quantities of elemental sulphur and many sulphur compounds, without their prior...     

Traceability as a tool aiding food safety assurance on the example of a food-packing plant

Accreditation and Quality Assurance - Enabling the possibility of “tracing” the route of a food product is a legal requirement for all participants of the food chain. It allows...     

New β-carotene-xylan complexes: preparation and characterization

Cellulose - The study aimed to propose a new system based on xylan for β-carotene delivery into aqueous environments. The xylan fraction of low molecular weight of...     

Gapmer Antisense Oligonucleotides Containing 2′,3′-Dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-d-lyxofuranosyl Nucleotides Display Site-Specific RNase H Cleavage and Induce Gene Silencing

Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing.     

Large-Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N-Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context

A large-scale synthesis of known Ru olefin metathesis catalyst VII featuring an unsymmetrical N-heterocyclic carbene (NHC) ligand with one 2,5-diisopropylphenyl (DIPP) and one thiophenylmethylene N-substituent is reported. The optimised procedure does not require column chromatography in any step and allows for preparation of up to 0.5 kg batches of the catalyst from simple precursors. The application profile of the obtained catalyst was studied in environmentally friendly dimethyl carbonate (DMC). Although VII exhibited low efficiency in cross-metathesis (CM) with electron-deficient partners, good to excellent results were noted for substrates featuring easy to isomerise C−C double bonds. This includes polyfunctional substrates of medicinal chemistry interest, such as analogues of psychoactive 5F-PB-22 and NM-2201 and two PDE5 inhibitors—Sildenafil and Vardenafil. Finally, a larger scale ring-closing metathesis (RCM) of a Vardenafil derivative was conducted in DMC, allowing for straightforward isolation of the expected product (23 g) in high yield and with low Ru contamination level (7.7 ppm).     

Novel Simultaneous Determination of Calcium and Magnesium Based on Flow Injection Gradient Titration

A novel approach based on flow injection gradient titration is proposed for the simultaneous spectrophotometric determination of Ca and Mg based on parameters of a single signal. Two reagents, calmagite and EDTA, are used to perform the determinations. Calmagite is introduced into a sample to form complexes with the analytes and the solutions are introduced into the holding coil of a sequential injection system in the sequence: carrier, air, sample, EDTA, and sample. In the system, EDTA replaces calmagite to form more stable complexes in turn with Ca and Mg. Next, the flow is reversed and the mixture is directed to the detector where the signal is measured at 680?nm. The signal consists of two parts: a short plateau (the signal for the sum of absorbance of complexes of Ca and Mg with calmagite) and a peak (the signal corresponding to titration of both complexes using EDTA). The absorbance values measured at the plateau and appropriately measured peak width were applied to determine analytes using two-component calibration. The method was verified for the determination of analytes in synthetic samples and in a certified reference material of surface water. Using the developed method, Mg and Ca were determined within the concentration ranges of 0.5–5.0 and 1.0–10.0?mg?L^?1, with precision better than 2.2 and 4.2% (relative standard deviation) and accuracy of 7.0 and 6.8% (relative error). The detection limits were 0.1 and 0.3?mg?L^?1 for Mg and Ca, respectively. The method was applied to analysis of mineral water samples.