Pillar[n]arenes are among the newest members of the macrocyclic family. Nevertheless, their conformational behavior and binding properties as well as redox properties of dealkylated pillar[n]arenes are well-studied. At the same time, introducing a heteroatom into a cyclophane macrocycle is already known to alter all the above properties drastically. This study presents a simple synthetic approach based on thia-Michael addition cyclization that readily resulted into hexathiapillar[6]arene with four phenylene units alternated by two redox-active hydroquinone moieties. The straightforward synthesis of the macrocycle enabled a systematic study of its conformation and redox behavior. The modification of hexathiapillar[6]arene afforded five functionalized derivatives, which were studied structurally in detail. The findings revealed interesting redox and structural properties of the macrocycle and its derivatives including the formation of crystal lattices with continuous channels and empty voids.
- Publikační typ
- časopisecké články MeSH
The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.
The dark web scene has been drawing the attention of law enforcement agencies and researchers alike. To date, most of the published works on the dark web are based on data gained by passive observation. To gain a more contextualized perspective, a study was conducted in which three vendors were selected on the "Dream Market" dark web marketplace, from whom subsequently several new psychoactive substances (NPS) were ordered. All transactions were documented from the initial drug deal solicitation to the final qualitative analysis of all received samples. From the selected vendors, a total of nine NPS samples was obtained, all of which were analyzed by NMR, HRMS, LC-UV, and two also by x-ray diffraction. According to our analyses, four of the five substances offered under already known NPS names contained a different NPS. The selected vendors therefore either did not know about their product, or deliberately deceived the buyers. Furthermore, two of three obtained samples of purportedly novel NPS were identified as already documented substances sold under a different name. However, the third characterized substance sold as "MPF-47700" was a novel, yet uncharacterized, NPS. Finally, we received a single undeclared substance, later identified as 5F-ADB. In addition to chemical analysis of the nine obtained NPS samples, the methodology used also yielded contextual information about the accessibility of NPS on the dark web, the associated purchase process, and the modus operandi of three NPS vendors. Direct participation in dark web marketplaces seems to provide additional layers of information useful for forensic studies.
- MeSH
- hmotnostní spektrometrie MeSH
- internet MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- obchodování s drogami * MeSH
- odhalování abúzu drog MeSH
- psychotropní léky analýza zásobování a distribuce MeSH
- spektrofotometrie ultrafialová MeSH
- zakázané drogy analýza zásobování a distribuce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Deschloroketamine (2-(methylamino)-2-phenyl-cyclohexanone) is a ketamine analog belonging to a group of dissociative anesthetics, which have been distributed within the illicit market since 2015. However, it was also being sold as 'ketamine' misleading people to believe that they were getting genuine ketamine. Dissociative anesthetics have also come to the attention of the psychiatric field due to their potential properties in the treatment of depression. At present, there is a dearth of information on deschloroketamine related to its metabolism, biodistribution, and its mechanism of action. We have therefore carried out a metabolomics study for deschloroketamine via non-targeted screening of urine samples employing liquid chromatography combined with high-resolution mass spectrometry. We developed and validated a multiple reaction monitoring method using a triple quadrupole instrument to track metabolites of deschloroketamine. Furthermore, significant metabolites of deschloroketamine, (trans-dihydrodeschloroketamine, cis- and trans-dihydronordeschloroketamine, and nordeschloroketamine), were synthesized in-house. The prepared standards were utilized in the developed multiple reaction monitoring method. The quantification method for serum samples provided intra-day accuracy ranging from 86% to 112% with precision of 3% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine were lower than 10 ng/mL, nordeschloroketamine and deschloroketamine ranged from 0.5 to 860 ng/mL in real samples. The quantification method for brain tissue provided intra-day accuracy ranging from 80% to 125% with precision of 7% on average. The concentrations of cis/trans-dihydronordeschloroketamines and trans-dihydrodeschloroketamine ranged from 0.5 to 70 ng/g, nordeschloroketamine and deschloroketamine varied from 0.5 to 4700 ng/g in real samples.
- MeSH
- chromatografie kapalinová MeSH
- ketamin agonisté krev chemická syntéza farmakokinetika MeSH
- krysa rodu rattus MeSH
- mozek metabolismus MeSH
- tandemová hmotnostní spektrometrie přístrojové vybavení MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Twenty juvenile individuals of brown bullhead (Ameiurus nebulosus), average weight 77 g, were fed by abiraterone acetate prodrug dissolved in olive oil via gastric probe. Dose applied was 3 mg/10 g fish weight. After feeding, they were let out into aquarium and kept there for 3 days. Aquarium water containing excreted metabolites was extracted, and sample was purified and finally analyzed by means of HPLC/MS. Expected both primary (products of hydroxylation) and secondary (products of glucuronidation and sulfatation) metabolites of abiraterone acetate were identified. The NMR measurement of one of the prevailing metabolites presumed to be one of possible hydroxy-abiraterones discovered that it is not hydroxy-abiraterone but abiraterone 16,17-epoxide. Closer analysis of MS2 and MS3 spectra revealed that one of presumed hydroxy-abiraterone acetates and also some secondary metabolites are probably 16,17-epoxides.
An aminoborane side product from the nicergoline manufacture process was identified by single-crystal X-ray diffraction. As boranes of pharmaceutical molecules are quite rare, the binding potential of the BH3 group was investigated and compared with similar compounds using Cambridge Structural Database (CSD). Surprisingly, the packing was stabilized by a dihydrogen bond, which triggered a false alert for too-short contact of hydrogen atoms in IUCR checkCIF. As the dihydrogen bond concept is not widely known, such an alert might mislead crystallographers to force -CH3 optimal geometry to -BH3 groups. The B-H distances equal to or less than 1.0 Å (17% of the CSD structures) are substantially biased when analyzing the structures of aminoborane complexes in CSD. To conduct proper searching, B-H bond length normalization should be applied in the CSD search.
Analysis of C cross-polarization magic angle spinning (CP/MAS) nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray powder diffraction data of trospium chloride (TCl) products crystallized from different mixtures of water-ethanol [φ(EtOH) = 0.5-1.0] at various temperatures (0°C, 20°C) and initial concentrations (saturated solution, 30%-50% excess of solvent) revealed extensive structural variability of TCl. Although (13) C CP/MAS NMR spectra indicated broad variety of structural phases arising from molecular disorder, temperature-modulated DSC identified presence of two distinct components in the products. FTIR spectra revealed alterations in the hydrogen bonding network (ionic hydrogen bond formation), whereas the X-ray diffraction reflected unchanged unit cell parameters. These results were explained by a two-component character of TCl products in which a dominant polymorphic form is accompanied by partly separated nanocrystalline domains of a secondary phase that does not provide clear Bragg reflections. These phases slightly differ in the degree of molecular disorder, in the quality of crystal lattice and hydrogen bonding network. It is also demonstrated that, for the quality control of such complex products, (13) C CP/MAS NMR spectroscopy combined with factor analysis (FA) can satisfactorily be used for categorizing the individual samples: FA of (13) C CP/MAS NMR spectra found clear relationships between the extent of molecular disorder and crystallization conditions. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1235-1248, 2013.
- MeSH
- benziláty chemie MeSH
- diferenciální skenovací kalorimetrie MeSH
- difrakce rentgenového záření MeSH
- krystalizace MeSH
- magnetická rezonanční spektroskopie MeSH
- nortropany chemie MeSH
- prášková difrakce MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A general method for Cu-catalyzed C-H sulfenylation of purines, 7-deaza- and 9-deazapurines with aryl- or alkyldisulfides has been developed. In purines, the reaction occurs at position 8, in 7-deazapurines at position 7 and in 9-deazapurines at position 9, leading to new interesting arylsulfanyl derivatives of purine or deazapurine bases. The resulting 8-arylsulfanylpurines undergo Liebesking-Srogl coupling with arylstannanes or boronic acids, whereas the (arylsulfanyl)deazapurines are not reactive under these conditions.
- MeSH
- krystalografie rentgenová MeSH
- měď chemie MeSH
- puriny chemie MeSH
- síra chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nostotrebin 6, a new polyphenolic compound with a fully substituted 2,2'-bis(cyclopent-4-en-1,3-dione) skeleton, was isolated from a methanolic extract of the cyanobacterial strain Nostoc sp. str. Lukesová 27/97. The structure of this compound was determined using X-ray crystallography and further supported by NMR, IR spectroscopy, and MS. Nostotrebin 6 is an S-parabolic I-parabolic noncompetitive inhibitor of acetylcholinesterase (IC(50) = 5.5 microM) and an S-parabolic I-parabolic mixed inhibitor of butyrylcholinesterase (IC(50) = 6.1-7.5 microM). The inhibitory potency of nostotrebin 6 was compared with that of tacrine and galanthamine.
- MeSH
- acetylcholinesterasa účinky léků MeSH
- butyrylcholinesterasa účinky léků MeSH
- cholinesterasové inhibitory chemie izolace a purifikace farmakologie MeSH
- cyklopentany chemie izolace a purifikace farmakologie MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- molekulární struktura MeSH
- Nostoc chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- financování organizované MeSH
- Publikační typ
- abstrakty MeSH
