Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® ChiraldexTM G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a LipodexTM D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility.1 As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the ChiraldexTM G-PN column. Six baseline and nine partial separations were observed with the LipodexTM D column, respectively.
In this work, the 3-D structure of the well-known opioid drug heroin in a solution was investigated. The goal was to provide a complete and detailed description of the stable conformers with their relative abundances. This knowledge is very important from the pharmaceutical and forensic point of view as it could help significantly with deeper understanding of heroin's metabolism and the development of antagonist medicines for the case of an overdose. As heroin is a chiral compound with five stereogenic centres, the methods of chiroptical spectroscopy supplemented by density functional theory (DFT) calculations were applied to study its conformations in chloroform solution. The selected chiroptical methods, namely, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD), are inherently sensitive to the 3-D structure of small- to medium-sized chiral organic molecules. A thorough conformational analysis revealed four stable conformers of heroin in chloroform solution, where the conductor-like polarizable continuum model of the solvent was used for all the calculations. The simulated ultraviolet (UV), infrared (IR), ECD, and VCD spectra were compared with the experimental ones and very good agreement was found, which enabled a detailed structure description and interpretation of the spectra. Chiroptical spectroscopy in combination with DFT calculations proved to be a very sensitive tool for the analysis of the 3-D structure of heroin in a solution in contrast with conventional spectroscopic methods. Especially, the application of VCD seems to be a promising approach for monitoring structural changes, for instance, those caused by solvents or interactions with other agents.
To enable the early diagnosis of pancreatic cancer, the search for and definition of reliable biomarkers remain a subject of great interest, with the specificity and sensitivity of the currently used biomarkers being below the required values. We tested a novel diagnostic approach for pancreatic cancer based on the specific molecular signature of blood plasma components. To acquire more detailed structural information, structure-sensitive chiroptical methods (electronic circular dichroism and Raman optical activity) were supplemented by conventional Raman and infrared spectroscopies. The obtained spectra were subsequently processed by linear discriminant analysis yielding high values of specificity and sensitivity. In addition, to monitor not only large biomolecules as potential biomarkers but also those of low molecular weight, we conducted an analysis of blood plasma samples by using metabolomics. The achieved results suggest a panel of promising biomarkers for a reliable detection of pancreatic cancer.
- MeSH
- cirkulární dichroismus * metody MeSH
- diskriminační analýza MeSH
- karnitin analogy a deriváty krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lysofosfatidylcholiny krev MeSH
- metabolomika * metody MeSH
- nádorové biomarkery krev MeSH
- nádory slinivky břišní * krev MeSH
- pilotní projekty MeSH
- Ramanova spektroskopie * metody MeSH
- senioři MeSH
- spektroskopie infračervená s Fourierovou transformací * metody MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- MeSH
- antiflogistika nesteroidní farmakokinetika chemie metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- jaterní mikrozomy metabolismus MeSH
- játra metabolismus MeSH
- kyselina máselná farmakokinetika chemie metabolismus MeSH
- morčata MeSH
- oxidace-redukce MeSH
- stereoizomerie MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- zvířata MeSH
- MeSH
- antiflogistika nesteroidní aplikace a dávkování chemie MeSH
- biotransformace MeSH
- finanční podpora výzkumu jako téma MeSH
- hepatocyty enzymologie metabolismus MeSH
- kastrace MeSH
- kyselina máselná aplikace a dávkování chemie MeSH
- oxidoreduktasy metabolismus MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
