ion-pairing
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Using molecular dynamics simulations in an explicit aqueous solvent, we examine the binding of fluoride versus iodide to a spherical macromolecule with both hydrophobic and positively charged patches. Rationalizing our observations, we divide the ion association interaction into two mechanisms: (1) poorly solvated iodide ions are attracted to hydrophobic surface patches, while (2) the strongly solvated fluoride and to a minor extent also iodide bind via cation-anion interactions. Quantitatively, the binding affinities vary significantly with the accessibility of the charged groups as well as the surface potential; therefore, we expect the ion-macromolecule association to be modulated by the local surface characteristics of the (bio-)macromolecule. The observed cation-anion pairing preference is in excellent agreement with experimental data.
Ion-pairing reversed-phase high-performance liquid chromatography (RP-HPLC) operation conditions were studied to obtain information useful for development and optimization of separation methods suitable for HPLC/MS analysis of dyes. The retention of eight sulphonated azodyes with widely differing structures (1-5 acid groups, molecular weight range 350-1220) was measured in mobile phases containing various ion-pairing reagents in aqueous-methanolic mobile phases. The effects of the type and of the concentration of ammonium acetate, tetrabutylammonium hydrogen sulphate and five di- and tri-alkylammonium acetate ion-pairing reagents on the chromatographic behaviour of dyes were compared in mobile phases with varying concentrations of methanol. Structural effects on the retention of dyes were studied in detail. The retention scale based on lipophilic and polar indices can be used for optimization of mobile phase for HPLC/MS of dyes and, on the other hand, may provide some information on the structure of unknown dyes.
Adefovir (9-(2-phosphonomethoxyethyl)adenine) is an acyclic nucleoside phosphonate currently used for the treatment of hepatitis B. The aim of this study was to evaluate the effect of permeation enhancer DDAK (6-dimethylaminohexanoic acid dodecyl ester) on the transdermal and topical delivery of adefovir. In porcine skin, DDAK enhanced adefovir flux 42 times with maximum at pH 5.8 suggesting ion pair formation. DDAK increased thermodynamic activity and stratum corneum/vehicle distribution coefficient of adefovir, as well as it directly decreased the skin barrier resistance. Maximal flux was observed already at 2% adefovir+1% DDAK. The results were confirmed in freshly excised human skin where DDAK enhanced adefovir flux 179 times to 8.9 microg/cm(2)/h. This rate of percutaneous absorption would allow for reaching effective plasma concentrations. After the topical application, adefovir concentrated in the stratum corneum with low penetration into the deeper skin layers from either aqueous or isopropyl myristate vehicle without the enhancer. With 1% DDAK, adefovir concentrations in the viable epidermis and dermis were 33-61 times higher. These results offer an attractive alternative to established routes of administration of adefovir and other acyclic nucleoside phosphonates.
- MeSH
- adenin analogy a deriváty aplikace a dávkování chemie metabolismus MeSH
- antivirové látky chemie metabolismus MeSH
- aplikace kožní MeSH
- difuzní komory kultivační MeSH
- druhová specificita MeSH
- farmaceutická chemie MeSH
- farmaceutická vehikula chemie MeSH
- kapronáty farmakologie chemie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- kožní absorpce účinky léků MeSH
- kůže metabolismus účinky léků MeSH
- lidé MeSH
- methylaminy farmakologie chemie MeSH
- organofosfonáty aplikace a dávkování chemie metabolismus MeSH
- permeabilita MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Bylo ověřeno použití 2,4-dinitrofenolu a 2,6-dinitrofenolu jako činidel při iontově párové extrakční spektrofotometrii kationických tenzidů prováděné zjednodušeným postupem (zkumavkovou metodou). Pro toto ověření byly v roli modelových stanovovaných látek použity čtyři kationické tenzidy. Po určení optimálních podmínek stanovení byl zkoumán vliv molárního přebytku obou činidel na absorbanci chloroformových výtřepků iontových párů. Byly zkonstruovány kalibrační křivky, byly odhadnuty kvantitativní limity a stanoveny zdánlivé molární absorpční koeficienty. Na základě získaných výsledků je možné doporučit oba zkoumané dinitrofenoly jako činidla vhodná ke studovanému účelu.
The application of 2,4-dinitrophenol and 2,6-dinitrophenol as reagents for a ion pair extraction spectrophotometry was tested. The ion pair extraction spectrophotometry experiments were carried out using a simplified procedure (test tube method). Four cationic tensides were used as model analytes. After the optimal conditions of the assay were being determined, the influence of the concentration excess of the reagents on the absorbance of the chloroform extract was investigated. Calibration curves were constructed; an estimation of limits of quantitation was performed and apparent molar absorption coefficients were determined. The obtained results show that both investigated dinitrophenols are suitable for the studied purpose.
The 22-mer c-kit promoter sequence folds into a parallel-stranded quadruplex with a unique structure, which has been elucidated by crystallographic and NMR methods and shows a high degree of structural conservation. We have carried out a series of extended (up to 10 μs long, ∼50 μs in total) molecular dynamics simulations to explore conformational stability and loop dynamics of this quadruplex. Unfolding no-salt simulations are consistent with a multi-pathway model of quadruplex folding and identify the single-nucleotide propeller loops as the most fragile part of the quadruplex. Thus, formation of propeller loops represents a peculiar atomistic aspect of quadruplex folding. Unbiased simulations reveal μs-scale transitions in the loops, which emphasizes the need for extended simulations in studies of quadruplex loops. We identify ion binding in the loops which may contribute to quadruplex stability. The long lateral-propeller loop is internally very stable but extensively fluctuates as a rigid entity. It creates a size-adaptable cleft between the loop and the stem, which can facilitate ligand binding. The stability gain by forming the internal network of GA base pairs and stacks of this loop may be dictating which of the many possible quadruplex topologies is observed in the ground state by this promoter quadruplex.
- MeSH
- denaturace nukleových kyselin MeSH
- draslík chemie MeSH
- G-kvadruplexy * MeSH
- kationty MeSH
- párování bází MeSH
- promotorové oblasti (genetika) * MeSH
- protoonkogenní proteiny c-kit genetika MeSH
- simulace molekulární dynamiky MeSH
- sodík chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The formation of intercalated motifs (iMs) - secondary DNA structures based on hemiprotonated C.C+ pairs in suitable cytosine-rich DNA sequences, is reflected by typical changes in CD and UV absorption spectra. By means of spectroscopic methods, electrophoresis, chemical modifications and other procedures, we characterized iM formation and stability in sequences with different cytosine block lengths interrupted by various numbers and types of nucleotides. Particular attention was paid to the formation of iMs at pH conditions close to neutral. We identified the optimal conditions and minimal requirements for iM formation in DNA sequences, and addressed gaps and inaccurate data interpretations in existing studies to specify principles of iM formation and modes of their folding.
- MeSH
- cytosin chemie metabolismus MeSH
- DNA chemie metabolismus MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- konformace nukleové kyseliny * MeSH
- nukleotidové motivy * MeSH
- párování bází MeSH
- sekvence nukleotidů MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A rapid procedure based on a direct extraction and HPLC determination with fluorescence detection of phenylephrine in pharmaceutical sachets that include a large excess of paracetamol (65 + 1, w/w), ascorbic acid (5 + 1, w/w), and other excipients (aspartame and sucrose) was developed and validated. The final optimized chromatographic method for ion-pair chromatography used an XTerra RP18 column, 3 microm particle size, 50 x 3.0 mm id. The mobile phase consisted of a mixture of acetonitrile and buffer (10 mM sodium octane-1-sulfonate, adjusted with H3PO4 to pH 2.2; 200 + 800, v/v), with a constant flow rate of 0.3 mL/min. The separation was carried out at 30 degrees C, and the injection volume was 3 microL. Fluorescence detection was performed at excitation and emission wavelengths of 275 and 310 nm, respectively. The mobile phase parameters, such as the organic solvent fraction (acetonitrile) in mobile phase as an organic modifier, the concentration of sodium octane-1-sulfonate as a counter-ion, temperature, and pH of mobile phase, were studied. As an alternative to ion-pair chromatography, hydrophilic interaction liquid chromatography (HILIC) was investigated using a Luna HILIC column, 3 microm, 100 x 4.6 mm id. The mobile phase consisted of acetonitrile and buffer (5 mM potassium dihydrogen phosphate, adjusted with H3PO4 to pH 2.5; 750 + 250, v/v) at a flow rate of 0.8 mL/min. The separation was carried out at 25 degrees C, and the injection volume was 5 microL. The proposed method has an advantage of a very simple sample pretreatment, and is much faster than the currently utilized HPLC methods using gradient elution and UV detection. Commercial samples of sachets were successfully analyzed by the proposed HPLC method.
