The many-body expansion approach to ab initio calculation of electric field gradients in molecular crystals.

Accurate calculation of electric field gradients (EFGs) in molecular crystals, despite big advances in ab initio techniques, is still a challenge. Here, we present a new approach to calculate the EFGs in molecular crystals by employing the many-body expansion (MBE) technique with electrostatic embedding. This allows for (i) a reduction in the computational cost or an alternative increase in the level of theory (we use the MP2/6-311++G) and (ii) the ability to monitor EFG convergence by progressively adding more surrounding molecules and/or adding higher many-body interactions. We focus on the 14N EFG and study four (model) compounds in more detail: solid nitrogen, ethylamine, methylamine, and ammonia. Solid nitrogen is rather insensitive to neighbors; for ethylamine and methylamine, the 3-body interactions are found sufficient for a converged EFG, whereas for ammonia, even the inclusion of 5-body interactions is insufficient although convergence is anticipated. We then validate our technique by comparing the experimental and ab initio14N EFGs for 116 organic compounds utilizing their known crystal structures and published EFG. Overall, we find a very good agreement, with a small EFG rms error, which is probably due to other sources, rather than the MBE approximation.

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.

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.

(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.

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.

Quantitative Analysis of Hydration Using Nitrogen-14 Nuclear Quadrupole Resonance.

Hydration is a quite common process in pharmaceutical solids. Sometimes it is desirable, as it stabilizes the crystal structure; in other cases it is unwanted, as it changes the physical and chemical properties of drugs. We here use (14)N NQR spectroscopy to quantitatively analyze hydration of a model compound, 5-aminotetrazole. (14)N NQR has some great advantages compared to other routinely used techniques to study hydration, like a very simple spectrum, single point calibration, and no need for special sample preparation, but the method's great disadvantage is a rather small sensitivity. Nevertheless, here we demonstrate that (14)N NQR, although being significantly less sensitive than XRD, NIR, and also (35)Cl NQR, is still capable of providing excellent quantitative accuracies. We can achieve errors <1% of the total amount, provided good temperature stabilization is implemented, which then allows long experimental times. We also present results obtained with a SLSE pulse sequence, which is a less robust approach but allows the use of much shorter measuring times (∼200×) and could be used for quantitative real time monitoring of hydration or dehydration.

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.

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.

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.

TNT detection with 14N NQR: multipulse sequences and matched filter.

Nuclear quadrupole resonance (NQR) has a distinct potential to verify the presence of nitrogen bearing substances based on the unequivocal signatures of their spectra. Therefore, this technique is especially suitable for remote detection of illicit substances and explosives. Unfortunately, the inherent signal-to-noise of the most abundant explosive trinitrotoluene (TNT) is very low. Here we present an NQR method with improved sensitivity for estimation of the probability of TNT presence in the investigated object. The method consists of a spin-lock spin-echo (SLSE) multipulse sequence for signal excitation and a time domain matched filter for signal detection. We find that the signal-to-noise increases by shortening the pulse spacings, even though this means a decrease in spectral resolution. In our case, the decrease of the pulse spacings from the typical 2 ms to 540 micros resulted in an increase of the signal-to-noise by 14 dB. A theory describing this enhancement is presented and compared to experimental results on TNT. Issues related to temperature and polymorphism variations are also discussed.

Relaxation during spin-lock spin-echo pulse sequence in (14)N nuclear quadrupole resonance.

In this work, we investigate off-resonance effect on the (14)N nuclear quadrupole resonance magnetization decay during the spin-lock spin-echo pulse sequence (SLSE). The compound chosen for this study is paranitrotoluene with a single (14)N site, which represents a suitable simplified model for the explosive trinitrotoluene with six nonequivalent (14)N sites. We find that the quasi-steady state magnetization exhibits dips at particular frequency offsets and more interestingly that its decay rate T(2 eff) (-1) exhibits similar dips (slower decay) at the same frequency offsets. The coexistence of dips is very important for applications where the primary use of the SLSE sequence is to increase the signal-to-noise ratio, as longer sampling times compensate for small magnetization values. A theory explaining both observations is presented which includes homonuclear dipolar interactions and spin coupling to the lattice. We show that the homonuclear dipolar interaction contributes only 20% to the total magnetization decay rate, while spin-lattice coupling is the dominant mechanism.

17O and 29Si NMR parameters of MgSiO3 phases from high-resolution solid-state NMR spectroscopy and first-principles calculations.

The 29Si and 17O NMR parameters of six polymorphs of MgSiO3 were determined through a combination of high-resolution solid-state NMR and first-principles gauge including projector augmented wave (GIPAW) formalism calculations using periodic boundary conditions. MgSiO3 is an important component of the Earth's mantle that undergoes structural changes as a function of pressure and temperature. For the lower pressure polymorphs (ortho-, clino-, and protoenstatite), all oxygen species in the 17O high-resolution triple-quantum magic angle spinning (MAS) NMR spectra were resolved and assigned. These assignments differ from those tentatively suggested in previous work on the basis of empirical experimental correlations. The higher pressure polymorphs of MgSiO3 (majorite, akimotoite, and perovskite) are stabilized at pressures corresponding to the Earth's transition zone and lower mantle, with perovskite being the major constituent at depths >660 km. We present the first 17O NMR data for these materials and confirm previous 29Si work in the literature. The use of high-resolution multiple-quantum MAS (MQMAS) and satellite-transition MAS (STMAS) experiments allows us to resolve distinct oxygen species, and full assignments are suggested. The six polymorphs exhibit a wide variety of structure types, providing an ideal opportunity to consider the variation of NMR parameters (both shielding and quadrupolar) with local structure, including changes in coordination number, local geometry (bond distances and angles), and bonding. For example, we find that, although there is a general correlation of increasing 17O chemical shift with increasing Si-O bond length, the shift observed also depends upon the exact coordination environment.