14N Nuclear Quadrupole Resonance Research Articles

Molecular motion of imidazolium cations and phase transitions in (ImH)2KCo(CN)6 with double perovskite structure

Temperature dependence of 1H nuclear magnetic resonance spin–lattice relaxation time T1 of (ImH)2KCo(CN)6, ImH+: imidazolium cation, is reported. The asymmetric T1 minimum observed in intermediate-temperature phase between 198 and 112 K is analyzed assuming the Cole-Davidson distribution of correlation time. Temperature dependences of 14N nuclear quadrupole resonance frequencies and spin–lattice relaxation times are also reported. The phase transitions at 198 and 112 K are shown to be of second and first order, respectively. The 14N relaxation is shown to be governed by the electric field gradient fluctuation due to the in-plane reorientational motion of the imidazolium cations.

The 1H [formula omitted] dispersion curve of fentanyl citrate to identify NQR parameters

We report the 1H T1 dispersion curve between 0 and 5 ​MHz for the synthetic opioid fentanyl citrate (C28H36N2O8). The structures in the curve can be used to estimate the 14N nuclear quadrupole resonance (NQR) frequencies of the material. Density functional theory predictions of the NQR parameters of several fentanyl citrate compounds are also reported. The predictions for the aniline nitrogen are consistent with structures in the observed T1 data. To help interpret the fentanyl citrate results the T1 dispersion curve for the explosive ammonium nitrate is also presented.

Nuclear Quadrupole Resonance (NQR)—A Useful Spectroscopic Tool in Pharmacy for the Study of Polymorphism

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.

14N NQR Quantification of Sodium Nitrite and Urotropin Using Singular Spectrum Analysis (SSA) for Data Filtering

An 14N nuclear quadrupole resonance (NQR) spectroscopy method has been developed using the singular spectrum analysis (SSA) based on the principal components concept. For the first time, it was demonstrated that this method can be used as a low cost and non-destructive quantitative method for analyses of small amounts (< 100 mg) of nitrogen containing solids. NQR technique is closely related to nuclear magnetic resonance, but without need for external magnetic field, applicable to solid compounds with quadrupolar nuclei. The hardware configuration using a broadband matching transformer was constructed and advanced algorithms for quantitative analyses of 14N NQR spectra were outlined. The calibration curves obtained, after optimization, for the model compounds, sodium nitrite and urotropin (hexamethylenetetramine), showed excellent linearity up to 500 mg for sodium nitrite at a frequency of 4642 kHz and up to 300 mg for urotropin at a frequency of 3307 kHz. The limits of detection were determined as 41 mg and 24 mg, respectively. The experimental and analytical procedure was simple enough to allow relatively easy practical implementation.

Motional freedom of dimethylammonium ions in a cyanoelpasolite, [(CH3)2NH2]2KCo(CN)6, which exhibits phase transition associated with a distinct change in dielectric property.

The temperature dependence of the 1H nuclear magnetic resonance spin-lattice relaxation time T1 of [(CH3)2NH2]2KCo(CN)6 and the partially deuterated analogue [(CD3)2NH2]2KCo(CN)6 has been reported. A change in the molecular motion of organic cations through the first-order phase transition at Tc = 246 K has been discussed. Although this first-order transition has been reported as an isosymmetric transition, in which the space group of the crystal does not change, the number of the 14N nuclear quadrupole resonance line changed from three in the high-temperature phase to twelve in the low-temperature phase indicating the lowering of crystal symmetry.

An optimized NQR spectrometer for detection of prohibited substances

Nuclear quadrupole resonance is a radio frequency spectroscopic technique which offers highly specific detection and is used in applications such as chemical analysis and security screening. This paper proposes a 14N nuclear quadrupole resonance system designed to detect prohibited substances in the frequency range of 0.4–6 MHz, using low-power and frequency sweeping excitation. The paper presents the system’s components and several technical solutions for noise reduction during data acquisition such as the use of fiber optic communication or battery-powered low-noise amplifiers. The detection system’s performance is evaluated using sodium nitrite and paracetamol, showing that the maximum detection distance for paracetamol is 2 cm and the minimum detection limit for sodium nitrite is 1 g at 7W transmitted power. Several solutions are proposed to further improve the detection system.

Polymorphism in Sulfanilamide: 14N Nuclear Quadrupole Resonance Study

To demonstrate the selectivity of 14N nuclear quadrupole resonance (14N NQR) spectroscopy in chemistry and pharmacy, a study of sulfanilamide polymorphism was undertaken. We studied 3 known polymorphs of sulfanilamide by 14N NQR. We found at room temperature 2 sets of 3 14N NQR transition frequencies, corresponding to 2 different nitrogen sites in the crystal structure for each of 3 polymorphs. We measured the temperature dependence of all quadrupole frequencies ν+, ν−. In each set, only 1 of the 3 14N NQR frequencies is enough to characterize the polymorph. Spin-lattice relaxation time (T1) measurement is supplemental information. We also measured the transition temperature between polymorphs and estimated the ratio of polymorphs after thermal treatment of sample.

A study of donor-acceptor interaction in halogen bonded complexes of N-iodosuccinimide by 14N NQR

Some halogen bonded complexes of N-iodosuccinimide (NIS) with the nitrogen atoms at the donor and acceptor positions have been investigated by 14N nuclear quadrupole resonance (NQR) spectroscopy. The data are analyzed in view of the change of the principal values of the quadrupole coupling tensor produced by halogen bonding. The results show that the deformation of the nitrogen electron orbitals is in the presently studied halogen bonded systems comparable to the one observed in strong hydrogen bonded systems. The order in which the strength of the halogen bond acceptor increases is determined. A possible iodine displacement to a position, which is closer to the acceptor nitrogen atom than to the donor nitrogen atom may occur in the complex NIS-(3-picoline). In all studied complexes the deformation of the nitrogen electron orbitals caused by the halogen bond decreases with increasing temperature at both the donor and acceptor nitrogen positions.

14N NQR spectroscopy reveals the proton position in N-HN bonds: a case study with proton sponges.

The position of protons in hydrogen bonds is often uncertain to some degree, as the technique most often used for structure determination, X-ray diffraction, is sensitive to electron density, which is not particularly abundant around protons. In hydrogen bonds, protons introduce an additional problem: the potential for proton motion is inherently anharmonic and thus requires the consideration of nuclear quantum effects (NQEs). Here, we demonstrate that 14N NQR spectroscopy is able to rather accurately determine proton positions in N-HN bonds, in certain cases with an accuracy comparable to that of X-ray and neutron diffraction at room temperature. We first derive, using ab initio calculations considering also the NQEs, a relation between the proton distance from the bond midpoint and the difference between the quadrupole coupling constants for the two nitrogen sites. The found relation is linear with a proportionality constant of 0.108 Å MHz-1 for tertiary amine nitrogens. Then, we validate our theoretical calculations experimentally, using several 1,8-bis(dimethylamino)naphthalene (DMAN) complexes.

An automated instrument for polarization-enhanced broadband nuclear quadrupole resonance (NQR) spectroscopy.

An automated instrument for improving the sensitivity of nuclear quadrupole resonance (NQR) spectroscopy is presented. The device is capable of pre-polarizing samples within a custom Halbach-type permanent magnet and then moving them into an external probe for zero-field NQR detection. Polarization transfer between protons and nitrogen (14N) nuclei in the sample occurs during demagnetization, thus increasing the amplitude of the detected NQR signals. The sample motion profile is completely programmable, thus providing a high level of control over the sample position and velocity for optimizing the polarization transfer process for various samples. Moreover, the magnet and motion controller are combined with a shielded sample probe and ultra-broadband front-end electronics (both designed in-house) to realize a complete scientific instrument for 14N NQR experiments. Compared with previous work in the field, the system is designed to be programmable, robust, and easy to use. Experimental results from several samples are also presented.

14N NQR lineshape in nanocrystals: An ab initio investigation of urea.

14N nuclear quadrupole resonance (NQR) lineshapes mostly contain information of low interest, although in nanocrystals they may display some unexpected behaviour. In this work, we present an ab initio computational study of the 14N NQR lineshapes in urea nanocrystals as a function of the nanocrystal size and geometry, focusing on the surface induced broadening of the lineshapes. The lineshapes were obtained through a calculation of the electric field gradient for each nitrogen site in the nanocrystal separately, taking into account the individual crystal field by embedding the molecule of interest in a suitable lattice of point multipoles representing other urea molecules in the nanocrystal. The small influence of distant molecules is found with a series expansion, using the in-crystal Sternheimer shieldings which we also calculated ab initio. We have considered nanocrystals with two geometries: a sphere and a cube, with characteristic sizes between 5 and 100 nm. Our calculations suggest that there is a dramatic difference between the linewidths for the two geometries. For spheres, we find a steep drop in linewidths at ∼10 nm; at 5 nm the linewidth is ∼11 kHz, whereas for sizes above 20 nm the linewidth is practically negligible (<100 Hz). For cubes, on the other hand, we find a steady 1/size decrease, from 12 kHz at 10 nm to 1.2 kHz at 100 nm. This analysis is important for 14N NQR spectroscopy of crystalline pharmaceuticals, where nanoparticles are increasingly more often embedded in some sort of matrix. Although this is only a theoretical analysis, we believe that this work can serve as a guidance for the forthcoming experimental analysis.

Broadband quantitative NQR for authentication of vitamins and dietary supplements

We describe hardware, pulse sequences, and algorithms for nuclear quadrupole resonance (NQR) spectroscopy of medicines and dietary supplements. Medicine and food safety is a pressing problem that has drawn more and more attention. NQR is an ideal technique for authenticating these substances because it is a non-invasive method for chemical identification. We have recently developed a broadband NQR front-end that can excite and detect 14N NQR signals over a wide frequency range; its operating frequency can be rapidly set by software, while sensitivity is comparable to conventional narrowband front-ends over the entire range. This front-end improves the accuracy of authentication by enabling multiple-frequency experiments. We have also developed calibration and signal processing techniques to convert measured NQR signal amplitudes into nuclear spin densities, thus enabling its use as a quantitative technique. Experimental results from several samples are used to illustrate the proposed methods.

Optical detection of low frequency NQR signals: a step forward from conventional NQR

In searching for the more sensitive 14N nuclear quadrupole resonance (NQR) detecting system for illicit substances, a promising combination of a classic RF pulse NQR spectrometer and a K optically pumped magnetometer was tested. The initial results are encouraging. The principles of such a combination are described, and the detection limits in the low frequency RF region, where the 14N pulse NQR frequencies are usually positioned, are presented. Several illicit substances which are difficult to detect with a classic pulse NQR spectrometer were detected with both types of spectrometers. We noticed that with the proposed combination of classic RF excitation of 14N nuclei, using a pulse NQR spectrometer and subsequent optical detection of the sample’s response, a gain in S/N of up to a factor of 10 was possible.

Nuclear Quadrupole Resonance Study of Proton and Deuteron Migration in Short Strong Hydrogen Bonds Formed in Molecular Complex 3,5-Dinitrobenzoic Acid–Nicotinic Acid and in Deuterated 3,5-Pyridinedicarboxylic Acid

Temperature dependences of the 14N nuclear quadrupole resonance (NQR) frequencies have been measured in molecular complex 3,5-dinitrobenzoic acid–nicotinic acid (35DBNA) and in deuterated 3,5-pyridinedicarboxylic acid (DPDA). In deuterated DPDA, the temperature dependences of the deuterium quadrupole coupling constants and asymmetry parameters η have also been measured. In 35DBNA, the magnitude of the quadrupole coupling constant of the pyridine nitrogen agrees with the experimentally observed proton transfer. No proton exchange (O–H···N ↔ O–···H–N+) is observed. The temperature dependence of the 14N quadrupole coupling constant is analyzed in a model of a resonance hybrid of two extreme electron configurations of the molecules. The energy difference of the two extreme electron configurations is determined. In the same model, we analyzed previously published 14N NQR data of the NHO hydrogen bond in nondeuterated 3,5-pyridinedicarboxylic acid. The 14N NQR data in DPDA show the presence of a quasi-continuou...

14N Nuclear Quadrupole Resonance Study of Piroxicam: Confirmation of New Polymorphic Form V

A new polymorphic crystal form of piroxicam was discovered while preparing crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR) analysis. The new crystal form, designated as V, was prepared by evaporative recrystallization from dichloromethane. Three known polymorphic forms (I, II, and III) were also prepared. Our aim was to apply (14) N NQR to characterize the new polymorphic form of piroxicam and compare the results with those of the other known polymorphic forms. Additional analytical methods used for characterization were X-ray powder diffraction (XRPD), thermal analysis, and vibrational spectroscopy. For the first time, a complete set of nine characteristic (14) N NQR frequencies was found for each prepared polymorph of piroxicam. The consistent set of measured frequencies and calculated characteristic quadrupole parameters found for the new polymorphic form V is a convincing evidence that we are dealing with a new form. The already known piroxicam polymorphic forms were characterized similarly. The XRPD results were in accordance with the conclusions of (14) N NQR analysis. The performed study clearly demonstrates a strong potential of (14) N NQR method to be applied as a highly discriminative spectroscopic analytical tool to characterize polymorphic forms.

14N NQR and relaxation in ammonium nitrate

The complete 14N nuclear quadrupole resonance (NQR) spectrum of ammonium nitrate is presented recorded using two double resonance techniques – double contact cross relaxation and zero field NQR. The spectra gave the quadrupole coupling constant (Qcc) and asymmetry parameter (η) values for the nitro of 611 kHz, 0.229 and that for the ammonium nitrogen of 242 kHz, 0.835. The three relaxation transition probabilities have been determined for both the nitro and ammonium nitrogen atoms. The bi-exponential relaxation times (T 1) were measured at 295 K. The values for nitro are 16.9 s and 10.5 s and that of the ammonium are 23.0 s and 16.4 s.

14 N NQR spectrum of sildenafil citrate

The 14N nuclear quadrupole resonance (NQR) spectrum of sildenafil citrate tablets has been recorded allowing the quadrupole coupling constants and asymmetry parameters of all six unique nitrogen atoms in its structure to be determined. A density function calculation gives results that are largely in agreement with the experimental values.

14N Nuclear Quadrupole Resonance Study of Polymorphism in Famotidine

(14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine was measured. At room temperature, seven quadrupolar sets of transition frequencies (ν(+), ν(-), and ν(0)) corresponding to seven different nitrogen sites in the crystal structure of each of the two polymorphs were found. This confirms the expected ability of NQR to distinguish polymorph B from its analog A. NQR can also measure their ratio in a solid mixture and in the final dosage form, that is, a tablet. The NQR frequencies, line shapes, and tentative assignation to all seven molecular (14)N atoms were obtained. Unravelment of these two entangled NQR spectra presents a valuable contribution to the NQR database and enables studies of some possible correlations therein. Moreover, nondestructive (14)N NQR studies of commercial famotidine tablets can reveal some details of the drug fabrication process connected with compression.

Theoretical 14N and 17O nuclear quadrupole resonance parameters for tirapazamine and related metabolites

Density functional theory (DFT) calculations were performed to realize the effects of the N–O group on the reactivity and electronic properties of 3-amino-1,2,4-benzotriazines. The electric field gradient, EFG, tensors of 14N and 17O nuclei and natural bond orbital (NBO) analysis in the tirapazamine (TPZ) and its four derivatives were calculated at the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) method in the gas phase. The NBO analysis reveal that the bond strength, proton affinity and position of N–O group in the heterocyclic ring have major influence on the reactivity of considered molecules. Accordingly, we suggest that the TPZ and 4-oxide (d) structures due to having a weaker N–O bond with larger negative charge on the oxygen atom at the 4-position are more active than the other ones. Calculated 14N and 17O EFG tensors were used to evaluate nuclear quadrupole coupling tensors, χ, and asymmetry parameters, η Q . Results showed that oxidation of a nitrogen atom at any position have significant influence on its 14N nuclear quadrupole resonance (NQR) parameters. Also, the occupancy of nitrogen lone pair plays an important role in determination of the q zz and χ values of mentioned nuclei. It is found that the η Q and χ are appropriate parameters to study the contribution of lone pair electrons of nitrogen atom in the formation of chemical bond or conjugation with the aromatic system. Finally, a linear correlation is observed between the χ(14N) and χ(17O) values in the N–O bond which may be associated with the reactivity of these compounds.

Nuclear Quadrupole Resonance Investigation of Hydrogen Bonding in Some Cocrystals of 2,3,5,6-Tetramethylpyrazine and Carboxylic Acids

Cocrystals of 2,3,5,6-tetramethylpyrazine and several carboxylic acids have been prepared, and the complete (14)N nuclear quadrupole resonance spectra have been measured. The (14)N nuclear quadrupole resonance spectra have been used to check whether the cocrystals are indeed formed and to investigate the hydrogen bonding scheme of 2,3,5,6-tetramethylpyrazine molecules. Since a 2,3,5,6-tetramethylpyrazine molecule has two hydrogen bond acceptors, it may form either 1:1 or 1:2 cocrystals with carbocylic acids. (14)N nuclear quadrupole resonance is used to distinguish between these two possibilities. Rather large (14)N quadrupole coupling constants in the investigated cocrystals show that in these systems proton transfer O-H···N → O(-)···H-N(+) does not occur. The quadrupole coupling tensor in 2,3,5,6-tetramethylpyrazine cocrystals has been analyzed in terms of the deformation of the electron lone pair orbital and population of the π-electron orbital. The analysis shows that the two effects are correlated.