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 O–H···N hydrogen bonds linking dimers and π–π 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 O–H···N bonds were characterized using 1H-17O and 1H-14N NQDR spectroscopies and QTAIM. The possibility of the existence of O–H···H–O 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 π···π stacking interactions

A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by 1H-14N NQDR and QTAIM/ DFT

A potential antileukemic and anticancer agent, 2-thiocytosine (2-TC), has been studied experimentally in the solid state by 1H-14N NMR-NQR double resonance (NQDR) and theoretically by the quantum theory of atoms in molecules (QTAIM)/density functional theory (DFT). Eighteen resonance frequencies on 14N were detected at 180 K and assigned to particular nitrogen sites (−NH2, –N=, and –NH–) in 2-thiocytosine. Factors such as the nonequivalence of molecules (connected to the duplication of sites) and possible prototropic tautomerism (capable of modifying the type of site due to proton transfer) were taken into account during frequency assignment. The result of replacing oxygen with sulfur, which leads to changes in the intermolecular interaction pattern and molecular aggregation, is discussed. This study demonstrates the advantages of combining NQDR and DFT to extract detailed information on the H-bonding properties of crystals with complex H-bonding networks. Solid-state properties were found to have a profound impact on the stabilities and reactivities of both compounds

Analysis of trees planted in vicinity of hospitals in Ljubljana as a source of pollen

The paper analyses woody plants growing in the vicinity of hospital buildings situated along Zalog Road, Korytko Street, Šlajmar Street, Bohorič Street and Njegoš Street in Ljubljana, Slovenia. Woody plants are an immediate potential source of allergenic pollen, affecting all park users such as patients, visitors and hospital employees. The most allergenic tree species in the park was found to be birch (Betula pendula Roth.), which accounts for 6.8% of all registered trees. The low allergenic maples (Acer sp.) and the low allergenic horse chestnut (Aesculus hippocastanum L.) account for 19.6% and 7.4%, respectively. Among the medium allergenic trees are ash (Fraxinus excelsior L.) (4.8%), plane (Platanus x hispanica Muenchh.) (4.2%), hornbeam (Carpinus betulus L.) (1.9%), and oak (Quercus sp.) and hazel (Corylus avellana L.) withless than 1%

Analiza drevja kot vira cvetnega prahu ob kliničnih bolnišnicah v Ljubljani

V prispevku so predstavljene lesnate rastline, ki rastejo v bližini bolnišničnih zgradb na Zaloški cesti ter na Korytkovi, Šlajmerjevi, Bohoričeviin Njegoševi ulici v Ljubljani. Lesnate rastline v parku so bližnji vir alergogenega cvetnega prahu, ki so mu izpostavljeni vsi uporabniki parka, bolniki, obiskovalci in zaposleno osebje. V parku je najbolj alergogena vrsta breza, ki predstavlja 6,8 % vseh dreves, 19,6 % je nizko alergogenih javorjev in 7,4 % nizko alergogenega divjega kostanja. Srednje visoko alergogeni so še jesen (4,8 %), platana (4,2 %), gaber (1,9 %) ter hrast in leska z manj kot 1-odstotno udeležbo.The paper analyses woody plants growing in the vicinity of hospital buildings situated along Zalog Road, Korytko Street, Šlajmar Street, Bohorič Street and Njegoš Street in Ljubljana, Slovenia. Woody plants are an immediate potential source of allergenic pollen, affecting all park users such as patients, visitors and hospital employees. The most allergenic tree species in the park was found to be birch (Betula pendula Roth.), which accounts for 6.8% of all registered trees. The low allergenic maples (Acer sp.) and the low allergenic horse chestnut (Aesculus hippocastanum L.) account for 19.6% and 7.4%, respectively. Among the medium allergenic trees are ash (Fraxinus excelsior L.) (4.8%), plane (Platanus x hispanica Muenchh.) (4.2%), hornbeam (Carpinus betulus L.) (1.9%), and oak (Quercus sp.) and hazel (Corylus avellana L.) withless than 1%

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 Alzheimer’s and Parkinson’s disease, and a promising drug for the treatment of post-COVID 2019 anosmia and ageusia, has been studied in the solid state and protein–ligand 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 resonance–nuclear 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 Pompeiu–Hausdorff 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 lines’ 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 Pompeiu–Hausdorff 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 protein–ligand complexes adopt the same methyl group conformation at N(7) as in the solid state. It was found that the cooperation–competition between the C-H⋯O hydrogen bonds and C-H⋯H-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 protein–ligand complexes

Nuclear Quadrupole Resonance (NQR)

Nuclear Quadrupole Resonance (NQR) spectroscopy has been known for 70 years. It is suitable for the study of measured (poly)crystalline chemical compounds containing quadrupole nuclei (nuclei with spin I ≥ 1) where the characteristic NQR frequencies represent the fingerprints of these compounds. In several cases, $^{14}$N NQR can distinguish between the polymorphic crystalline phases of active pharmaceutical ingredients (APIs). In order to further stimulate $^{14}$N NQR studies, we review here several results of API polymorphism studies obtained in Ljubljana laboratories: (a) In sulfanilamide, a clear distinction between three known polymorphs (α, β, γ) was demonstrated. (b) In famotidine, the full spectra of all seven different nitrogen positions were measuredtwo polymorphs were distinguished. (c) In piroxicam, the $^{14}$N NQR data helped in confirming the new polymorphic form V. (d) The compaction pressure in the tablet production of paracetamol, which is connected with linewidth change, can be used to distinguish between producers of paracetamol. We established that paracetamol in the tablets of six different manufacturers can be identified by $^{14}$N NQR linewidth. (e) Finally, in order to get an extremely sensitive $^{14}$N NQR spectrometer, the optical detection of the $^{14}$N NQR signal is mentioned