Butterfly Effect in Cytarabine: Combined NMR-NQR Experiment, Solid-State Computational Modeling, Quantitative Structure-Property Relationships and Molecular Docking Study.

Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA synthesis. The minor structural alteration (the inversion of hydroxyl at the 2' positions of the sugar) leads to change of the biological activity from anti-depressant and DNA/RNA block builder to powerful anti-cancer. Our study aimed to determine the molecular nature of this phenomenon. Three 1H-14N NMR-NQR experimental techniques, followed by solid-state computational modelling (Quantum Theory of Atoms in Molecules, Reduced Density Gradient and 3D Hirshfeld surfaces), Quantitative Structure-Property Relationships, Spackman's Hirshfeld surfaces and Molecular Docking were used. Multifaceted analysis-combining experiments, computational modeling and molecular docking-provides deep insight into three-dimensional packing at the atomic and molecular levels, but is challenging. A spectrum with nine lines indicating the existence of three chemically inequivalent nitrogen sites in the Ara-C molecule was recorded, and the lines were assigned to them. The influence of the structural alteration on the NQR parameters was modeled in the solid (GGA/RPBE). For the comprehensive description of the nature of these interactions several factors were considered, including relative reactivity and the involvement of heavy atoms in various non-covalent interactions. The binding modes in the solid state and complex with dCK were investigated using the novel approaches: radial plots, heatmaps and root-mean-square deviation of the binding mode. We identified the intramolecular OH···O hydrogen bond as the key factor responsible for forcing the glycone conformation and strengthening NH···O bonds with Gln97, Asp133 and Ara128, and stacking with Phe137. The titular butterfly effect is associated with both the inversion and the presence of this intramolecular hydrogen bond. Our study elucidates the differences in the binding modes of Ara-C and cytidine, which should guide the design of more potent anti-cancer and anti-viral analogues.

Elucidating the Role of Noncovalent Interactions in Favipiravir, a Drug Active against Various Human RNA Viruses; a 1H-14N NQDR/Periodic DFT/QTAIM/RDS/3D Hirshfeld Surfaces Combined Study.

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.

Observing short-range orientational order in small-molecule liquids.

Local molecular ordering in liquids has attracted a lot of interest from researchers investigating crystallization, but is still poorly understood on the molecular scale. Classical nucleation theory (CNT), a macroscopic thermodynamic description of condensation, has shortcomings when dealing with clusters consisting of tens of molecules. Cluster formation and local order fluctuations in liquid media are difficult to study due to the limited spatial resolution of electron- and photon-imaging methods. We used NMR relaxometry to demonstrate the existence of dynamic clusters with short-range orientational order in nominally isotropic liquids consisting of elongated molecules. We observed clusters in liquids where the local ordering is driven by polar, steric, and hydrogen-bond interactions between the molecules. In the case of a liquid crystal, measuring the local orientational order fluctuations allowed us to observe the size of these clusters diverging when approaching the phase transition from the isotropic to the nematic phase. These fluctuations are described in terms of rotational elasticity as a consequence of the correlated reorientations of the neighbouring molecules. Our quantitative observations of the dynamic clusters in liquids, numbering about ten or fewer molecules, indicate that this is a general phenomenon in various types of liquids.

Sensitivity of Proton NMR Relaxation and Proton NMR Diffusion Measurements to Olive Oil Adulterations with Vegetable Oils.

Olive oils and, in particular, extra-virgin olive oils (EVOOs) are one of the most frauded food. Among the different adulterations of EVOOs, the mixture of high-quality olive oils with vegetable oils is one of the most common in the market. The need for fast and cheap techniques able to detect extra-virgin olive oil adulterations was the main motivation for the present research work based on 1H NMR relaxation and diffusion measurements. In particular, the 1H NMR relaxation times, T1 and T2, measured at 2 and 100 MHz on about 60 EVOO samples produced in Italy are compared with those measured on four different vegetable oils, produced from macadamia nuts, linseeds, sunflower seeds, and soybeans. Self-diffusion coefficients on this set of olive oils and vegetable oil samples were measured by means of the 1H NMR diffusion ordered spectroscopy (DOSY) technique, showing that, except for the macadamia oil, other vegetable oils are characterized by an average diffusion coefficient sensibly different from extra-virgin olive oils. Preliminary tests based on both NMR relaxation and diffusometry methods indicate that eventual adulterations of EVOO with linseed oil and macadamia oil are the easiest and the most difficult frauds to be detected, respectively.

Analysis of Extra Virgin Olive Oils from Two Italian Regions by Means of Proton Nuclear Magnetic Resonance Relaxation and Relaxometry Measurements.

The interest in development of new non-destructive methods for characterization of extra virgin olive oils (EVOOs) has been increasing in the recent years. Among different experimental techniques, nuclear magnetic resonance (NMR) relaxation measurements are very promising in the field of food characterization and authentication. In this study, we focused on relaxation times T1 and T2 measured at different magnetic field strengths (namely, 2, 100, and 400 MHz) and 1H NMR T1 relaxometry dispersions directly on olive oil samples without any chemical/physical treatments. A large set of EVOO samples produced in two regions of Italy, Tuscany and Apulia, were investigated by means of 1H NMR relaxation techniques. The relaxation studies reported here show several common features between the two sets of EVOO samples, thus indicating that relaxation properties, namely, the ranges of values of T1 and T2 at 2 and 100 MHz, are characteristic of EVOOs, independently from the cultivars, climate, and geographic origin. This is a promising result in view of quality control and monitoring.

NMR and NQR study of polymorphism in carbamazepine.

Four polymorphic forms of carbamazepine have been simultaneously investigated by 1H NMR and 14N NQR. The results show that the proton spin-lattice relaxation time and the 14N NQR spectra can be used to differentiate between various polymorphic forms. Spontaneous transformations from Form II to Form III and from Form IV to Form III have been investigated through their influence on the 14N NQR spectrum and the proton NMR signal and spin-lattice relaxation. The 14N NQR spectra prove that in the observed polymorphic forms of carbamazepine the hydrogen bonded dimers of carbamazepine molecules are the basic elements of the crystal structure. The dimers are centrosymmetric in Forms III and IV and in metastable polymorphic form occurring during the transformation of Form IV to Form III. Two non-equivalent molecular positions are observed in Form II with the occupation ratio 1:1 and in Form I with the occupation ratio either 2:1 or 3:1. The 14N NQR data are related to the published crystal structures. Possible reasons for the mismatch of the X-ray and NQR data for Forms I and II are discussed.

Dynamics of water and xanthan chains in hydrogels studied by NMR relaxometry and their influence on drug release.

The dynamic properties of water and polymer molecules in xanthan hydrogels at different polymer mass fractions were investigated through the combination of conventional and fast-field cycling NMR relaxation to obtain the information about dynamics in different time scales. The results showed that water dynamics were faster in diluted than in concentrated hydrogels. However, the type of polymer-chain dynamics did not change for xanthan fractions from 0.1 to 0.5, although they slowed at higher xanthan fractions as the system approached transition to the glass state. The addition of the nonionic small drug molecules pentoxifylline did not change the dynamics in the hydrogels, but they were affected by the medium pH. The water and polymer-chain dynamics were faster in the hydrogels for the neutral than the acid medium. These differences resulted in slower swelling and thinner and more rigid hydrogel layer of the matrix tablet in the acid medium that was less susceptible to erosion. Consequently, pentoxifylline release from xanthan tablets in acid medium is dominated by drug diffusion. At neutral pH, the molecular mobility is greater, which resulted in rapid and extensive swelling of the hydrogel, leading to erosion-dominated drug release.

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.

Molecular dynamics of 1-ethyl-3-methylimidazolium triflate ionic liquid studied by 1H and 19F nuclear magnetic resonances.

The molecular dynamics of an ionic liquid (IL) composed of a 1-ethyl-3-methylimidazolium cation and a triflate (trifluoromethanesulfonate) anion, abbreviated as [Emim][TfO], were studied by NMR spectroscopy. By measuring the temperature-dependent high-field 1H and 19F spin-lattice relaxation (SLR) rates, the frequency-dependent 1H and 19F SLR dispersion curves using fast-field-cycling relaxometry, and the temperature-dependent 1H and 19F diffusion constants, and by utilizing the fact that the primary NMR-active nucleus on the Emim cation is 1H, whereas on the TfO anion it is 19F, the cationic and anionic dynamics were studied separately. A single theoretical relaxation model successfully reproduced all the experimental data of both types of resonant nuclei by fitting all the data simultaneously with the same set of fit parameters. Upon cooling, [Emim][TfO] exhibited a supercooled liquid phase between TSL = 256 K and the crystallization temperature TCr ≈ 227-222 K, as confirmed by differential scanning calorimetry (DSC) experiments. Theoretical analysis revealed that within the liquid and the supercooled liquid states of [Emim][TfO], the 1H and 19F relaxation rates are affected by both the rotational and translational diffusional processes with no discontinuous change at TSL. While the rotational diffusion is well described as an Arrhenius thermally activated process, the translational diffusion undergoes strong freezing dynamics that are well described by the Vogel-Fulcher model assuming a freezing temperature of T0 = 157 K. The existence of the supercooled liquid region in the [Emim][TfO] IL should be taken into account when using this IL for a specific application.

Multifunctional Gadolinium-Doped Mesoporous TiO2 Nanobeads: Photoluminescence, Enhanced Spin Relaxation, and Reactive Oxygen Species Photogeneration, Beneficial for Cancer Diagnosis and Treatment.

Materials with controllable multifunctional abilities for optical imaging (OI) and magnetic resonant imaging (MRI) that also can be used in photodynamic therapy are very interesting for future applications. Mesoporous TiO2 sub-micrometer particles are doped with gadolinium to improve photoluminescence functionality and spin relaxation for MRI, with the added benefit of enhanced generation of reactive oxygen species (ROS). The Gd-doped TiO2 exhibits red emission at 637 nm that is beneficial for OI and significantly improves MRI relaxation times, with a beneficial decrease in spin-lattice and spin-spin relaxation times. Density functional theory calculations show that Gd3+ ions introduce impurity energy levels inside the bandgap of anatase TiO2 , and also create dipoles that are beneficial for charge separation and decreased electron-hole recombination in the doped lattice. The Gd-doped TiO2 nanobeads (NBs) show enhanced ability for ROS monitored via • OH radical photogeneration, in comparison with undoped TiO2 nanobeads and TiO2 P25, for Gd-doping up to 10%. Cellular internalization and biocompatibility of TiO2 @xGd NBs are tested in vitro on MG-63 human osteosarcoma cells, showing full biocompatibility. After photoactivation of the particles, anticancer trace by means of ROS photogeneration is observed just after 3 min irradiation.

(1)H-(14)N cross-relaxation spectrum analysis in sildenafil and sildenafil citrate.

Here we describe a method for the extraction of (14)N quadrupole parameters from a (1)H-(14)N cross-relaxation spectrum by fitting the lineshapes of the (14)N quadrupole transitions. The procedures used typically to fit quadrupole lineshapes are not directly applicable to fit the (1)H-(14)N cross-relaxation spectrum, because the presence of proton homonuclear dipolar interaction broadens the lineshapes considerably and prevents a reliable determination of Cq and η from a single lineshape. Instead, one must fit two or even three lineshapes originating from the same nitrogen site simultaneously. The problem is to identify which lineshapes belong together when many are observed due to the existence of several nitrogen sites. We solve this problem by fitting the spectrum for all possible combinations and find the best-fitting one. This combination then most likely correctly identifies lineshapes belonging to the same nitrogen site. There are two main advantages of our method compared to the typically used method, which relies only on lineshape singularities: (i) the method is "automatic" and does not require knowledge of nitrogen quadrupole parameters in similar environments to aid dip pairing and (ii) the accuracy of quadrupole parameters is better, as proton linewidth is included in the fits. We use sildenafil and sildenafil citrate as model compounds, each with six non-equivalent nitrogen sites.

Dry-cured ham tissue characterization by fast field cycling NMR relaxometry and quantitative magnetization transfer.

Fast field cycling (FFC) and quantitative magnetization transfer (qMT) NMR methods are two powerful tools in NMR analysis of biological tissues. The qMT method is well established in biomedical NMR applications, while the FFC method is often used in investigations of molecular dynamics on which longitudinal NMR relaxation times of the investigated material critically depend. Despite their proven analytical potential, these two methods were rarely used in NMR studies of food, especially when combined together. In our study, we demonstrate the feasibility of a combined FFC/qMT-NMR approach for the fast and nondestructive characterization of dry-curing ham tissues differing by protein content. The characterization is based on quantifying the pure quadrupolar peak area (area under the quadrupolar contribution of dispersion curve obtained by FFC-NMR) and the restricted magnetization pool size (obtained by qMT-NMR). Both quantities correlate well with concentration of partially immobilized, nitrogen-containing and proton magnetization exchanging muscle proteins. Therefore, these two quantities could serve as potential markers for dry-curing process monitoring. Copyright © 2016 John Wiley & Sons, Ltd.

(1)H NMR Relaxometric Study of Molecular Dynamics in a "de Vries" Liquid Crystal.

Liquid crystals that exhibit de Vries smectic A phases are promising materials for new generations of ferroelectric liquid crystal displays and other electro-optical devices. We investigated the molecular dynamic properties of a rod-like de Vries liquid crystal compound, namely the 9HL, a (S)-hexyl lactate derivative, in the whole mesophasic range. This is the first molecular dynamics' investigation on a de Vries phase, and the interest of this system is related to the understanding of the structural and supramolecular organization of de Vries SmA phases, which has been a subject of a broad scientific debate in the last years. Proton NMR spin-lattice relaxation times, T1, were measured in the range 100 MHz to 5 kHz, thus covering a very wide range of motional regimes. (1)H NMR dispersion curves and temperature-dependent relaxation rates were analyzed with a global minimum target fitting approach and the main molecular motions, namely reorientational diffusion, translational self-diffusion, layer undulation, and tilting director fluctuations were fully characterized. The molecular dynamics' behavior observed across the SmA-SmC* phase transitions of 9HL was consistent with the proposed cluster diffuse cone model for the de Vries SmA phase.

Polymorphism and disorder in natural active ingredients. Low and high-temperature phases of anhydrous caffeine: Spectroscopic ((1)H-(14)N NMR-NQR/(14)N NQR) and solid-state computational modelling (DFT/QTAIM/RDS) study.

The polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) has been studied by (1)H-(14)N NMR-NQR (Nuclear Magnetic Resonance-Nuclear Quadrupole Resonance) double resonance and pure (14)N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form ß) and metastable (phase I, form α) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT. The shifts of the NQR frequencies, quadrupole coupling constants and asymmetry parameters at each nitrogen site due to polymorphic transition were evaluated. The strongest shifts were observed at N(3) site, while the smallest at N(9) site. The commercial pharmaceutical sample was found to contain approximately 20-25% of phase I and 75-80% of phase II. The orientational disorder in phase II with a local molecular arrangement mimics that in phase I. Substantial differences in the intermolecular interaction phases I and II of caffeine were analysed using computational (DFT/QTAIM/RDS) approach. The analysis of local environment of each nitrogen nucleus permitted drawing some conclusions on the topology of interactions in both polymorphs. For the most stable orientations in phase I and phase II the maps of the principal component qz of EFG tensor and its asymmetry parameter at each point of the molecular system were calculated and visualized. The relevant maps calculated for both phases I and II indicates small variation in electrostatic potential upon phase change. Small differences between packings in phases slightly disturb the neighbourhood of the N(1) and N(7) nitrogens, thus are meaningless from the biological point of view. The composition of two phases in pharmaceutical material should not be any obstacle, which is relevant from the pharmaceutical industry point of view.

WURST-QCPMG sequence and "spin-lock" in ¹4N nuclear quadrupole resonance.

¹4N nuclear quadrupole resonance (NQR) is a promising method for the analysis of pharmaceuticals or for the detection of nitrogen based illicit compounds, but so far, the technique is still not widely used, mostly due to the very low sensitivity. This problem is already acute in the preliminary NQR stage, when a compound is being examined for the first time and the NQR frequencies are being searched for, by scanning a wide frequency range step-by-step. In the present work, we experimentally show how to increase the efficiency of this initial stage by using a combination of a wideband excitation achieved with frequency swept pulses (WURST) and a "spin-lock" state obtained with a quadrupolar-CPMG (QCPMG) sequence. In the first part we show that WURST pulses provide a much larger excitation bandwidth compared to common rectangular pulses. This increased bandwidth allows to increase the frequency step and reduces the total number of steps in a scanning stage. In the second part we show that the "spin-lock" decay time T2eff obtained with the WURST-QCPMG combination is practically identical with the T2eff obtained with the most common "spin-lock" sequence, the SLSE, despite a very different nature and length of excitation pulses. This allows for a substantial S/N increase through echo averaging in every individual step and really allows to exploit all the advantages of the wider excitation in the NQR frequency scanning stage. Our experimental results were obtained on a sample of trinitrotoluene, but identical behavior is expected for all compounds where a "spin-lock" state can be created.

Phase transition and ring-puckering motion in a metal-organic perovskite [(CH2)3NH2][Zn(HCOO)3].

Phase transitions in a metal-organic perovskite with an azetidinium cation, which exhibits giant polarizability, were investigated using differential scanning calorimetry (DSC) and (1)H nuclear magnetic resonance (NMR) measurements. The DSC results indicated successive phase transitions at 254 and 299 K. The temperature dependence of the spin-lattice relaxation time T(1) determined by NMR indicated that the activation energy for cation ring-puckering motion was 25 kJ mol(-1) in phase I (T > 299 K). The potential energy at the transition state of puckering is expected to decrease when the potential for the motion becomes asymmetric with decreasing temperature in phases II and III. A possible mechanism for the onset of an extraordinarily large dielectric anomaly is discussed.

Capacitor-based detection of nuclear magnetization: nuclear quadrupole resonance of surfaces.

We demonstrate excitation and detection of nuclear magnetization in a nuclear quadrupole resonance (NQR) experiment with a parallel plate capacitor, where the sample is located between the two capacitor plates and not in a coil as usually. While the sensitivity of this capacitor-based detection is found lower compared to an optimal coil-based detection of the same amount of sample, it becomes comparable in the case of very thin samples and even advantageous in the proximity of conducting bodies. This capacitor-based setup may find its application in acquisition of NQR signals from the surface layers on conducting bodies or in a portable tightly integrated nuclear magnetic resonance sensor.

1H NMR relaxometry study of a rod-like chiral liquid crystal in its isotropic, cholesteric, TGBA*, and TGBC* phases.

The molecular dynamics of a chiral liquid crystal showing a rich variety of frustrated mesophases has been investigated by means of 1H NMR relaxometry. The interest in this lactate derivative, HZL 7/*, is related to a large range of thermal stabilities of the twist grain boundary (TGB) phases. Dispersions of the 1H spin-lattice relaxation times, T1, in the frequency range from 300 MHz to 5 kHz were measured and consistently analyzed in the isotropic, chiral nematic, TGBA*, and two TGBC* phases. In the isotropic and N* phases, a three-exponential magnetization decay was observed and assigned to three specific molecular groups of the HZL 7/* (molecular core, methyl, and methylene groups). In the TGB phases, all T1 components merge into a single one. The analysis of the T1 dispersion in the TGBA* phase shows that the translational self-diffusion relaxation mechanism dominates over a broad frequency range and that layer undulations are less relevant than the relaxation contribution associated with the diffusion process across the TGB structure. In the TGBC1* phase, the T1 dispersion presents a strong contribution of in-layer tilt direction fluctuations (T1(-1) proportional to ν(-1/2)), while, in the TGBC2* phase, the linear frequency dependence of T1 could be associated with a much stronger contribution of layer undulations than for the other TGB phases. This is at present the first molecular dynamics investigation on several TGB phases by means of 1H NMR relaxometry.

Aplicability of TNT "super-Q detection" to multipulse sequences.

The use of high-Q probes to increase the sensitivity in NMR and NQR is a well-known technique, however very high Q values are associated with several limitations. This paper explores the (14)N NQR multipulse detection of trinitrotoluene (TNT) signal-to-noise ratio as a function of the pickup coil Q factor, with a particular emphasis on the "super-Q" regime, where probe bandwidth becomes narrower than the NQR linewidths. We have used a mixed experimental-theoretical approach to find the TNT Q-dependent signal-to-noise value which avoided the inconvenient construction of a probe at every Q. The process has been repeated for a range of excitation/detection frequencies and a 2D sensitivity map was obtained. Our analysis suggests, that sensitivity is maximum and practically Q-independent when 400

Improving 14N nuclear quadrupole resonance detection of trinitrotoluene using off-resonance effects.

The off-resonance dependence of the amplitudes of the six dominant (14)N nuclear quadrupole resonance (NQR) lines in commercial polymorphic trinitrotoluene (TNT) sample were experimentally determined for a wide range of experimental parameters when irradiated with the spin-lock spin-echo (SLSE) pulse sequence. We find that the amplitudes off-resonance dependence follows a sinc-like function with an additional modulation due to the spacing between the RF pulses. This dependence can be very well modeled with expressions we have derived for a single site (14)N NQR in paranitrotoluene (PNT). The results can be immediately used for the reduction of the number of free parameters used in the robust signal processing models for the TNT NQR detectors.