12 research outputs found
Introductory Chapter: Caffeine, a Major Component of Nectar of the Gods and Favourite Beverage of Kings, Popes, Artists and Revolutionists, a Drug or a Poison?
Introductory Chapter: Having a Brain is Not Necessary to Get Cancer⊠but Indispensable to Fight It
Supramolecular synthon pattern in solid clioquinol and cloxiquine (APIs of antibacterial, antifungal, antiaging and antituberculosis drugs) studied by 35Cl NQR, 1H-17O and 1H-14N NQDR and DFT/QTAIM
The quinolinol derivatives clioquinol (5-chloro-7-iodo-8-quinolinol, Quinoform) and cloxiquine (5-chloro-8-quinolinol) were studied experimentally in the solid state via 35Cl NQR, 1H-17O and 1H-14N NQDR spectroscopies, and theoretically by density functional theory (DFT). The supramolecular synthon pattern of OâH···N hydrogen bonds linking dimers and ÏâÏ stacking interactions were described within the QTAIM (quantum theory of atoms in molecules) /DFT (density functional theory) formalism. Both proton donor and acceptor sites in OâH···N bonds were characterized using 1H-17O and 1H-14N NQDR spectroscopies and QTAIM. The possibility of the existence of OâH···HâO dihydrogen bonds was excluded. The weak intermolecular interactions in the crystals of clioquinol and cloxiquine were detected and examined. The results obtained in this work suggest that considerable differences in the NQR parameters for the planar and twisted supramolecular synthons permit differentiation between specific polymorphic forms, and indicate that the more planar supramolecular synthons are accompanied by a greater number of weaker hydrogen bonds linking them and stronger ÏÂ·Â·Â·Ï stacking interactions
WyobraĆŒenia studentĂłw medycyny o przyszĆym zawodzie a model lekarza podstawowej opieki zdrowotnej
W niniejszej pracy skoncentrowano siÄ na prĂłbie okreĆlenia czynnikĂłw sprzyjajÄ
cych ksztaĆtowaniu siÄ wĆaĆciwych wyobraĆŒeĆ o zawodzie lekarza u studentĂłw medycyny, czyli takich, ktĂłre w sferze postulowanych cech lekarza byĆyby bliskie aktualnemu modelowi lekarza, natomiast w sferze postrzegania realiĂłw zawodu stanowiĆyby ich odzwierciedlenie. Celem poĆrednim byĆo poznanie wyobraĆŒeĆ studentĂłw medycyny o zawodzie lekarza
Exploring Partial Structural Disorder in Anhydrous Paraxanthine through Combined Experiment, Solid-State Computational Modelling, and Molecular Docking
Paraxanthine (PX), a major metabolite of caffeine, a protective agent against Alzheimerâs and Parkinsonâs disease, and a promising drug for the treatment of post-COVID 2019 anosmia and ageusia, has been studied in the solid state and proteinâligand complex. Partial disorder in PX, caused by the methyl group at the N(7) position, has been modelled and discussed. The relationship between the unusual structural disorder and the propensity to form a specific system of non-covalent bonds was analyzed. Three 1H-14N NMR-NQR (nuclear magnetic resonanceânuclear quadrupole resonance) experimental techniques were used, namely multiple frequency sweeps, Larmor frequency scanning, and the two-frequency irradiation, followed by solid-state computational modelling (density functional theory, supplemented by quantum theory of atoms in molecules, 3D Hirshfeld surfaces, and reduced density gradient), and molecular docking approaches. New quantitative methods for estimating changes in the global pattern of interactions under the influence of rotation of the methyl group in N(7) based on the PompeiuâHausdorff and Bhattacharayya metrics and the Wasserstein distance have been proposed and applied. A spectrum consisting of 12 lines, indicating the presence of 4 chemically inequivalent nitrogen sites in the PX molecule, was recorded, and the linesâ assignment to particular sites was made. The influence of the methyl rotation on the eigenvalues and eigenvectors of the electric field gradient tensor, NQR parameters, and resonance line positions was modelled in the solid (GGA/RPBE, m-GGA/RSCAN) and cluster (Minnesota M062X hybrid). Three factors have been found to determine structural disorder in PX: larger crystal voids near the methyl at N(7) than at N(1) (opening the path for the disorder), hyperconjugation strongly affecting the density distribution in the five-membered ring, and the involvement of the methyl group at N(7) in many non-covalent bonds that intercept (capture) subsequent jumping protons. The PompeiuâHausdorff and Bhattacharayya metrics and the Wasserstein distance confirmed the changes in the distribution and strength of non-covalent interactions throughout the molecule as a result of methyl rotation. This effect is clearly visible regardless of the type of metric, and its order of magnitude is consistent with the modulation effect of the NQR spectra (experimental and calculated). Through molecular docking, it was discovered that the PX moiety in proteinâligand complexes adopt the same methyl group conformation at N(7) as in the solid state. It was found that the cooperationâcompetition between the C-HâŻO hydrogen bonds and C-HâŻH-C dispersion interactions is the crucial factor that impedes methyl rotation and induces structural disorder, as well as being an important factor in the formation of the proteinâligand complexes