Maria Książek

Spectroscopic characterization and crystal structures of two cathinone derivatives: N-ethyl-2-amino-1-phenylpropan-1-one (ethcathinone) hydrochloride and N-ethyl-2-amino-1-(4-chlorophenyl)propan-1-one (4-CEC) hydrochloride

Comprehensive chemical characterization for two cathinone derivatives, N-ethyl-2-amino-1-phenylpropan-1-one (ethcathinone) hydrochloride and N-ethyl-2-amino-1-(4-chlorophenyl)-propan-1-one (4-chloroethcathinone, 4-CEC) hydrochloride, in material seized by drug enforcement agencies was performed by nuclear magnetic resonance (NMR) spectroscopy, infrared spectroscopy, gas chromatography–mass spectrometry in positive electron ionization mode, liquid chromatography–mass spectrometry in positive electrospray ionization mode and X-ray crystallography. The examined samples of these two compounds proved to be very pure for ethcathinone and mixed with very small quantities of other substances for 4-CEC by NMR spectroscopy and mass spectrometry. X-ray crystallographic studies confirmed the occurrence of both compounds as racemic mixtures. These spectroscopic and crystallographic data seem very useful for their identification. Especially for 4-CEC, this is the first description on its spectroscopic characterization in a scientific context to our knowledge.

Synthesis, Structure and Cytotoxic Activity of Mono- and Dialkoxy Derivatives of 5,8-Quinolinedione.

A series of 5,8-quinolinedione derivatives containing one or two alkoxy groups was synthesized and characterized by 1H- and 13C-NMR, IR and MS spectra. X-ray diffraction was used to investigate the crystal structures of 6-chloro-7-(2-cyjanoethoxy)-5,8-quinolinedione and 6,7-di(2,2,2-trifloroethoxy)-5,8-quinolinedione. All studied compounds were tested in vitro for their antiproliferative activity against three human cancer cell lines and human normal fibroblasts. Most of the compounds showed higher cytotoxicity than the starting compound, 6,7-dichloro-5,8-quinolinedione, and cisplatin, which was used as a reference agent.

Spectroscopic and crystallographic characterization of two cathinone derivatives: 1-(4-fluorophenyl)-2-(methylamino)pentan-1-one (4-FPD) hydrochloride and 1-(4-methylphenyl)-2-(ethylamino)pentan-1-one (4-MEAP) hydrochloride

PurposeIn this study, we performed identification and physicochemical characterization of two cathinone derivatives, 4-FPD and 4-MEAP, found in market-available materials.MethodsThe compounds were characterized by electrospray ionization ion trap mass spectrometry (MS) in MS2 and MS3 modes, gas chromatography–MS, infrared, Raman and ultraviolet-visible spectroscopies, X-ray crystallography, differential scanning calorimetry and nuclear magnetic resonance spectroscopy.ResultsWe could obtain detailed and comprehensive physicochemical characterization of 4-FPD and 4-MEAP—new cathinone derivatives available on the designer drugs market.ConclusionsDynamic growth in the number of psychoactive substances available on the designer drug markets makes it compulsory to obtain analytical data allowing unequivocal identification of these drugs in the fastest possible way. In this study we presented analytical data useful in quick identification of the investigated compounds.

Structural determinants influencing halogen bonding: a case study on azinesulfonamide analogs of aripiprazole as 5-HT 1A , 5-HT 7 , and D 2 receptor ligands

A series of azinesulfonamide derivatives of long-chain arylpiperazines with variable-length alkylene spacers between sulfonamide and 4-arylpiperazine moiety is designed, synthesized, and biologically evaluated. In vitro methods are used to determine their affinity for serotonin 5-HT1A, 5-HT6, 5-HT7, and dopamine D2 receptors. X-ray analysis, two-dimensional NMR conformational studies, and docking into the 5-HT1A and 5-HT7 receptor models are then conducted to investigate the conformational preferences of selected serotonin receptor ligands in different environments. The bent conformation of tetramethylene derivatives is found in a solid state, in dimethyl sulfoxide, and as a global energy minimum during conformational analysis in a simulated water environment. Furthermore, ligand geometry in top-scored complexes is also bent, with one torsion angle in the spacer (τ2) in synclinal conformation. Molecular docking studies indicate the role of halogen bonding in complexes of the most potent ligands and target receptors.

Spectroscopic characterization and crystal structures of two cathinone derivatives: 1-(4-chlorophenyl)-2-(1-pyrrolidinyl)-pentan-1-one (4-chloro-α-PVP) sulfate and 1-(4-methylphenyl)-2-(dimethylamino)-propan-1-one (4-MDMC) hydrochloride salts, seized on illicit drug market

PurposeTwo compounds newly found in the seizures by drug enforcement agencies were identified and characterized by various instrumental analytical methods.MethodsThe obtained powder samples were analyzed by gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometryn (LC–MSn), nuclear magnetic resonance (NMR) spectroscopy, infrared and Raman spectroscopy and X-ray crystallography.ResultsThe two compounds were tentatively identified as 4-chloro-α-PVP and 4-MDMC by GC–MS, and LC–MS/MS. The confirmation of the results was made by NMR spectroscopy. The X-ray crystallography gave information that 4-chloro-α-PVP and 4-MDMC were in salted forms with sulfate and hydrochloride, respectively; in addition, both compounds existed as racemic mixtures.ConclusionsWe could identify 4-chloro-α-PVP and 4-MDMC in the seizure powder samples by various analytical methods. X-ray crystallography was especially useful for identifying the salted forms and enantiomeric forms.

Crystal structures and other properties of ephedrone (methcathinone) hydrochloride, N-acetylephedrine and N-acetylephedrone

PurposeThree compounds obtained from ephedrine were identified and characterized by various instrumental analytical methods. Ephedrone (methcathinone) hydrochloride and its fundamental derivatives N-acetylephedrine and N-acetylephedrone were analyzed as precursors of a cathinone derivative.MethodsThe obtained samples were analyzed by gas chromatography coupled with mass spectrometry, nuclear magnetic resonance spectroscopy, infrared and Raman spectroscopy, and X-ray crystallography.ResultsThe three compounds were confirmed as: N-methyl-2-amino-1-phenylpropan-1-one (methcathinone) hydrochloride, N-acetyl-N-methyl-2-amino-1-phenylpropan-1-one (cathinone derivative), and N-acetyl-N-methyl-2-amino-1-phenylpropan-1-ol (acetyl derivative of ephedrine).ConclusionsX-ray crystallography is especially useful for identifying the new designer drugs and their different precursor forms.

Polymorphs of oxindole as the core structures in bioactive compounds

A new polymorph of oxindole (termed as “δ-form”) has been found and characterized by single-crystal X-ray diffraction. Its structural properties were compared with those of the previously reported polymorphs (the α-, β- and γ-forms). This polymorphic form was crystallized for the first time but could not be reproduced. Thus, the δ-form can serve as an example of a “disappearing polymorph”. As a result, the three previously reported α-, β- and γ-forms have now been characterized by powder X-ray diffraction, vibrational spectroscopy (infrared and Raman) and calorimetry (differential scanning calorimetry). In the structures of the earlier known α- and β-forms, N–H⋯O hydrogen bonds connect the molecules into dimers, while the crystals of the γ- and δ-forms contain hydrogen-bonded chains of associated molecules. An analysis of the Hirshfeld surfaces and fingerprint plots has also been performed to study the intermolecular interactions in the crystal network of each polymorph. The spectroscopic and thermal investigations showed that the polymorphs convert into the α-form, which indicates that the α-form is the most stable at ambient temperature. Additionally, the α- and β-forms are enantiotropically-related phases, whereas the γ-form is monotropically related to the α-form. Unexpectedly, the β- and γ-forms were found to be unstable under Cu Kα radiation and both gradually transformed into the α-form with the γ-phase being more stable.