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, ¹⁴N NQR can distinguish between the polymorphic crystalline phases of active pharmaceutical ingredients (APIs). In order to further stimulate ¹⁴N 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 measured; two polymorphs were distinguished. (c) In piroxicam, the ¹⁴N 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 ¹⁴N NQR linewidth. (e) Finally, in order to get an extremely sensitive ¹⁴N NQR spectrometer, the optical detection of the ¹⁴N NQR signal is mentioned.

The ${}_{}{}^{39}{}_{}{}^{}\mathrm{K}$ electric field gradient (EFG) and chemical-shift tensors have been determined in KSCN above and below ${\mathit{T}}_{\mathit{c}}$. Whereas all the data below ${\mathit{T}}_{\mathit{c}}$ are compatible with the site symmetry of the ${\mathrm{K}}^{+}$ ions given by the space group ${\mathit{D}}_{2\mathit{h}}^{11}$ (Pbcm) of the low-temperature orthorhombic phase, this is not the case for the EFG data above ${\mathit{T}}_{\mathit{c}}$. The symmetry of the paraelectric phase is broken on the quadrupole-coupling time scale but not on the chemical-shift-tensor time scale, allowing for an interesting insight into the dynamics of the ${\mathrm{SCN}}^{\mathrm{-}}$ head-tail disordering process. The transition is of the order-disorder type for the ${\mathrm{SCN}}^{\mathrm{-}}$ groups and of a displacive type for the ${\mathrm{K}}^{+}$ ions.

Combination of proton-nitrogen level crossing polarization transfer and pulsed spin-locking sequence makes ${}^{14}\mathrm{N}$ nuclear quadrupole resonance (NQR) in trinitrotoluene fast and sensitive enough to be used in routine detection of explosives. Enhancement factors for all three ${}^{14}\mathrm{N}$ NQR lines (the case with $\eta \ne 0$ ) were calculated and compared with experimental values. Good agreement between measured and calculated signal enhancement factors was observed. ${}^{14}\mathrm{N}$ NQR signals in a $15\mathrm{g}$ trinitrotoluene sample of predominantly monoclinic modification were measured in $15\mathrm{s}$ in different polarization magnetic fields. The conditions for optimal proton-nitrogen level crossing were determined.

In this work, we report a study of two thermotropic liquid crystalline samples showing a not common mesophase behavior. The samples, namely a di-benzyloxy biphenyl derivative labelled 9/2 RS/RS, and a bimesogenic liquid crystal labelled L1, show a direct transition between two isotropic phases followed, at lower temperatures, by the optically isotropic, 3D structured, cubic phase. These systems have been investigated by means of ¹H NMR diffusometry and ¹H NMR relaxometry in order to characterize their isotropic–isotropic’–cubic mesophase behavior, mainly on the dynamic point of view. In particular, the temperature trend of the self-diffusion coefficients measured for both samples allowed us to significantly distinguish between the two isotropic phases, while the temperature dependence of the ¹H spin-lattice relaxation time (T₁) did not show significant discontinuities at the isotropic–isotropic’ phase transition. A preliminary analysis of the frequency-dependence of ¹H T₁ at different temperatures gives information about the main motional processes active in the isotropic mesophases.

Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely ¹H-¹⁴N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied. The complete NQR spectrum consisting of nine lines indicating the presence of three chemically inequivalent nitrogen sites in the FPV molecule was detected, and the assignment of lines to particular sites was performed. The description of the nearest vicinity of all three nitrogen atoms was used to characterize the nature of the intermolecular interactions from the perspective of the local single atoms and to draw some conclusions on the nature of the interactions required for effective recognition and binding. The propensity to form the electrostatic N−H···O, N−H···N, and C−H···O intermolecular hydrogen bonds competitive with two intramolecular hydrogen bonds, strong O−H···O and very weak N−H···N, closing the 5-member ring and stiffening the structure, as well as π···π and F···F dispersive interactions, were analysed in detail. The hypothesis regarding the similarity of the interaction pattern in the solid and the RNA template was verified. It was discovered that the -NH₂ group in the crystal participates in intermolecular hydrogen bonds N–H···N and N–H···O, in the precatalytic state only in N–H···O, while in the active state in N–H···N and N–H···O hydrogen bonds, which is of importance to link FVP to the RNA template. Our study elucidates the binding modes of FVP (in crystal, precatalytic, and active forms) in detail and should guide the design of more potent analogues targeting SARS-CoV-2. Strong direct binding of FVP-RTP to both the active site and cofactor discovered by us suggests a possible alternative, allosteric mechanism of FVP action, which may explain the scattering of the results of clinical trials or the synergistic effect observed in combined treatment against SARS-CoV-2.