Tamás Németh

Determination of paracetamol and its main impurity 4-aminophenol in analgesic preparations by micellar electrokinetic chromatography

A micellar electrokinetic chromatographic (MEKC) method was developed for the quality control of paracetamol containing pharmaceutical preparations. The influence of several factors (surfactant concentration, buffer concentration, pH and applied voltage) was studied during development and optimisation of the method. Phosphate buffer (pH 9.0) containing sodium dodecyl sulphate (75 mM) was found as the ideal running buffer for the separation; the applied voltage was 25 kV and the analysis time was 10 min. The limit of quantitation for 4-aminophenol was 6 microgml(-1); the linearity of the method was studied in the concentration ranges 20-260 microgml(-1) for paracetamol and 20-150 microgml(-1) for 4-aminophenol. The method was successfully applied for the quality control of paracetamol containing products.

Preparation and Studies of Chiral Stationary Phases Containing Enantiopure Acridino-18-Crown-6 Ether Selectors

The enantiomeric separation ability of the newly prepared chiral stationary phases containing acridino-18-crown-6 ether selectors was studied by high-performance liquid chromatography (HPLC). The chiral stationary phases separated the enantiomers of selected protonated primary aralkylamines efficiently. The best results were found for the separation of the mixtures of enantiomers of NO2 -PEA.

A Novel Method for the Preparation of a Chiral Stationary Phase Containing an Enantiopure Acridino-18-Crown-6 Ether Selector

This paper reports a novel method for the preparation of chiral stationary phases (CSPs) using an acridino-18-crown-6 ether selector as a model compound. Chiral stationary phase (R,R)-CSP- 2A: was obtained by in situ continuously recirculating the solution of carboxyl-substituted acridino-18-crown-6 ether (R,R)- 4: , dicyclohexylcarbodiimide and 3-(triethoxysilyl)propylamine through a high-performance liquid chromatography (HPLC) column containing blank silica gel in elevated pressure and temperature. The enantiomer separating ability of chiral stationary phase (R,R)-CSP- 2A: was investigated by HPLC using mixtures of enantiomers of 1-(1-naphthyl)ethylamine hydrogen perchlorate, 1-(2-naphthyl)ethylamine, 1-(4-bromophenyl)ethylamine and 1-(4-nitrophenyl)ethylamine hydrogen chloride. The best results were found for the separation of the mixtures of enantiomers of Br-PEA.

Synthesis and cation binding of acridono-18-crown-6 ether type ligands

The synthesis of a new acridono-18-crown-6 ether type sensor has been carried out starting from commercially available and relatively cheap materials. The cation recognition ability of the new ligand and also a reported analog thereof toward various metal ions was studied in acetonitrile by UV/Vis spectroscopy. Our studies revealed the selective binding of Pb2+ ions by the latter ligand. Based on our calculations, we suggest the formation of a complex with 1:1 ligand to metal ion ratio.Graphical abstract

Structural characterization of the crystalline diastereomeric complexes of enantiopure dimethylacridino-18-crown-6 ether and the enantiomers of 1-(1-naphthyl)ethylamine hydrogen perchlorate

This paper describes the X-ray crystal structure of the diastereomeric complexes formed by enantiopure dimethyl-substituted acridino-18-crown-6 ether (R,R)-1 and the enantiomers of 1-(1-naphthyl)ethylammonium perchlorate. We found that the heterochiral complex (R,R)-1–(S)-1-NEA is more stable than the homochiral one (R,R)-1–(R)-1-NEA. In the case of the heterochiral complex, the X-ray studies revealed a strong intermolecular π–π interaction between the naphthyl unit and the acridine moiety. However, in the case of the homochiral complex, π–π interaction was not found. We suggest that the existence or absence of the π–π interaction and the difference in steric repulsions in the diastereomers is responsible for the enantiomeric discrimination.

Akridon és akridin egységet tartalmazó koronaéter alapú szenzor- és szelektormolekulák szintézise, kation- és enantiomerfelismerése

Napjainkban széleskörû tudományos érdeklõdés irányul a különbözõ fémionok, illetve királis vegyületek enantiomerjeinek egyre szelektívebb felismerését biztosító szenzormolekulák, valamint az ezek elválasztását is lehetõvé tevõ szelektormolekulák kifejlesztésére, mivel alkalmazásukra a gyógyszeriparban, az élelmiszeriparban és a környezetvédelemben is lehetõség nyílik. Ezen vegyületek szelektív komplexképzõ tulajdonságainak alapja a molekuláris felismerés jelensége, amely a legjobban két vagy több molekula közötti szelektív megkülönböztetésként jellemezhetõ, amely során másodlagos (nem kovalens) kölcsönhatások kialakulása révén rendezett szerkezetek, komplexek keletkeznek. A molekuláris felismerés fogalmát Emil Fischer dolgozta ki 1894-ben, mikor egy adott enzim adott szubsztráthoz való specifikus kötõdését a „kulcs-zár” elmélettel magyarázta. A szupramolekuláris kémia fogalmának bevezetése pedig Jean-Marie Lehn nevéhez fûzõdik: véleménye szerint ez úgy határozható meg, mint “kémia a molekulán túl”1. Az egyre szélesebb körben terjedõ szupramolekuláris kémia másodlagos kötõerõkkel összetartott molekuláris asszociátumok keletkezésével, tulajdonságainak és alkalmazási lehetõségeinek vizsgálatával foglalkozik. Mióta az egyik úttörõje az ilyen irányú kutatásoknak, Charles J. Pedersen, publikálta az elsõ szintetikus gazdamolekulák, a koronaéterek szintézisét és vizsgálatát2,3, ez a kutatási terület jelentõs érdeklõdésre tett szert4. E terület elismerését jelzi, hogy a nagy szelektivitással rendelkezõ szerkezet-specifikus kölcsönhatások kialakítására képes molekulák kifejlesztésért Charles J. Pedersennek, Donald J. Cramnek és Jean-Marie Lehnnek ítélték oda az 1987. évi kémiai Nobel-díjat. A 2016. évi kémiai Nobel-díjat Jean-Pierre Sauvage, Sir J. Fraser Stoddart és Bernard L. Feringa kapta molekuláris gépek fejlesztéséért, amely azt mutatja, hogy a kémia e területe most is nagy érdeklõdésre tart számot.

Applicability evaluation of advanced processes for elimination of neurophysiological activity of antidepressant fluoxetine

Presence of the antidepressant fluoxetine in different water bodies has raised significant concerns due to its detrimental effects on non-targeted organisms, especially on fish. When seeking for an appropriate technology able to remove fluoxetine residue from a complex water matrix, special attention needs to be paid to the elimination of the neurophysiological activity that eventually lies behind the noxious effects of the parent compound. Our aim was to probe the applicability of advanced oxidation techniques for this purpose using in situ generated free radical system based on OH-initiated peroxyl radical-mediated processes. By performing product analysis experiments along with quantum chemical calculations, the most probable reaction paths were analyzed including aromatic hydroxylation, defluorination, O-dealkylation and C-dealkylation. The candidates for neurophysiological activity were further investigated by molecular docking. The hydroxylated derivatives are well accommodated in the binding pocket of the corresponding protein, suggesting that these compounds may retain the activity of the parent compound. From a worst-case perspective, we suggest that prolonged treatment needs to be applied to further transform hydroxylated derivatives.

Synthesis and pKa determination of new enantiopure dimethyl‐substituted acridino‐crown ethers containing a carboxyl group: Useful candidates for enantiomeric recognition studies

New enantiopure dimethyl-substituted acridino-18-crown-6 and acridino-21-crown-7 ethers containing a carboxyl group at position 9 of the acridine ring [(S,S)-8, (S,S)-9, (R,R)-10] were synthesized. The pKa values of the new crown ethers [(S,S)-8, (S,S)-9, (R,R)-10] and of an earlier reported macrocycle [(R,R)-2] were determined by UV-pH titrations. Crown ether (S,S)-8 was attached to silica gel by covalent bonds and the enantiomeric separation ability of the newly prepared chiral stationary phase [(S,S)-CSP-12] was studied by high-performance liquid chromatography (HPLC). Homochiral preference was observed and the best separation was achieved for the enantiomers of 1-NEA. Ligands (S,S)-9 and (R,R)-10 are precursors of enantioselective sensor and selector molecules for the enantiomers of protonated primary amines, amino acids, and their derivatives.

Application of Flow Chemistry to Macrocyclization of Crown Ethers

This paper reports a new continuous-flow synthesis of chiral and achiral pyridino-18-crown-6 ethers. Macrocyclizations have been performed in a packed-bed flow reactor where deprotonation of a bifunctional primary or a secondary alcohol takes place with potassium hydroxide as a heterogeneous base avoiding the use of stronger and more dangerous one, sodium hydride. Ditosylate derivatives of pyridine as precursors for the macrocyclization used in batch condition were replaced by the appropriate diiodides and optimization of the parameters provided higher yields in shorter reaction times. The setup presented here is suitable for the preparation of different ethers by Williamsontype syntheses in continuous-flow reactions.