NMR Quadrupole Research Articles

Detection of helical water flows in sub-nanometer channels

Nanoscale flows of liquids can be revealed in various biological processes and underlie a wide range of nanofluidic applications. Though the integral characteristics of these systems, such as permeability and effective diffusion coefficient, can be measured in experiments, the behaviour of the flows within nanochannels is still a matter of speculation. Herein, we used a combination of quadrupolar solid-state NMR spectroscopy, computer simulation, and dynamic vapour sorption measurements to analyse water diffusion inside peptide nanochannels. We detected a helical water flow coexisting with a conventional axial flow that are independent of each other, immiscible, and associated with diffusion coefficients that may differ up to 3 orders of magnitude. The trajectory of the helical flow is dictated by the screw-like distribution of ionic groups within the channel walls, while its flux is governed by external water vapour pressure. Similar flows may occur in other types of nanochannels containing helicoidally distributed ionic groups and be exploited in various nanofluidic lab-on-a-chip devices.

Quadrupolar NMR crystallography guided crystal structure prediction (QNMRX-CSP)

35Cl (I = 3/2) solid-state NMR data is used in a nascent quadrupolar NMR crystallographic protocol, dubbed QNMRX-CSP, for the structural prediction, refinement, and validation of organic HCl salts.

Characterization of ephedrine HCl and pseudoephedrine HCl using quadrupolar NMR crystallography guided crystal structure prediction

We report a quadrupolar guided NMR crystallography crystal structure prediction protocol as applied for pseudoephedrine HCl and ephedrine HCl. We explore the crystal structure prediction of pseudoephedrine HCl in the dosage form.

Superstructure and Correlated Na+ Hopping in a Layered Mg-Substituted Sodium Manganate Battery Cathode are Driven by Local Electroneutrality.

In this work, we present a variable-temperature 23Na NMR and variable-temperature and variable-frequency electron paramagnetic resonance (EPR) analysis of the local structure of a layered P2 Na-ion battery cathode material, Na0.67[Mg0.28Mn0.72]O2 (NMMO). For the first time, we elucidate the superstructure in this material by using synchrotron X-ray diffraction and total neutron scattering and show that this superstructure is consistent with NMR and EPR spectra. To complement our experimental data, we carry out ab initio calculations of the quadrupolar and hyperfine 23Na NMR shifts, the Na+ ion hopping energy barriers, and the EPR g-tensors. We also describe an in-house simulation script for modeling the effects of ionic mobility on variable-temperature NMR spectra and use our simulations to interpret the experimental spectra, available upon request. We find long-zigzag-type Na ordering with two different types of Na sites, one with high mobility and the other with low mobility, and reconcile the tendency toward Na+/vacancy ordering to the preservation of local electroneutrality. The combined magnetic resonance methodology for studying local paramagnetic environments from the perspective of electron and nuclear spins will be useful for examining the local structures of materials for devices.

Indirectly detected satellite-transition quadrupolar NMR via progressive saturation of the proton reservoir

Static satellite-transitions (ST) NMR line shapes from half-integer quadrupolar nuclei could be very informative: they can deliver insight about local motions over a wide range of timescales, and can report on small changes in the local electronic environments as reflected by variations in the quadrupolar parameters. Satellite transitions, however, are typically “invisible” for half-integer quadrupolar nuclei due to their sheer breadth, leading to low signal-to-noise ratio –especially for unreceptive low-gamma or dilute quadrupolar nuclei. Very recently we have introduced a method for enhancing the NMR sensitivity of unreceptive X nuclei in static solids dubbed PROgressive Saturation of the Proton Reservoir (PROSPR), which opens the possibility of magnifying the signals from such spins by repeatedly imprinting frequency-selective X-driven depolarizations on the much more sensitive 1H NMR signal. Here, we show that PROSPR's efficacy is high enough for enabling the detection of static ST NMR for challenging species like 35Cl, 33S and even 17O –all at natural-abundance. The ensuing ST-PROSPR NMR experiment thus opens new approaches to probe ultra-wideline (6–8 MHz wide) spectra. These highly pronounced anisotropies can in turn deliver new vistas about dynamic changes in solids, as here illustrated by tracking ST line shapes as a function of temperature during thermally-driven events.

A Complete Picture of Cation Dynamics in Hybrid Perovskite Materials from Solid-State NMR Spectroscopy.

The organic cations in hybrid organic-inorganic perovskites rotate rapidly inside the cuboctahedral cavities formed by the inorganic lattice, influencing optoelectronic properties. Here, we provide a complete quantitative picture of cation dynamics for formamidinium-based perovskites and mixed-cation compositions, which are the most widely used and promising absorber layers for perovskite solar cells today. We use 2H and 14N quadrupolar solid-state NMR relaxometry under magic-angle spinning to determine the activation energy (Ea) and correlation time (τc) at room temperature for rotation about each principal axis of a series of organic cations. Specifically, we investigate methylammonium (MA+), formamidinium (FA+), and guanidinium (GUA+) cations in current state-of-the-art single- and multi-cation perovskite compositions. We find that MA+, FA+, and GUA+ all have at least one component of rotation that occurs on the picosecond timescale at room temperature, with MA+ and GUA+ also exhibiting faster and slower components, respectively. The cation dynamics depend on the symmetry of the inorganic lattice but are found to be insensitive to the degree of cation substitution. In particular, the FA+ rotation is invariant across all compositions studied here, when sufficiently above the phase transition temperature. We further identify an unusual relaxation mechanism for the 2H of MA+ in mechanosynthesized FAxMA1-xPbI3, which was found to result from physical diffusion to paramagnetic defects. This precise picture of cation dynamics will enable better understanding of the relationship between the organic cations and the optoelectronic properties of perovskites, guiding the design principles for more efficient perovskite solar cells in the future.

Metal Binding to Sodium Heparin Monitored by Quadrupolar NMR.

Heparins and heparan sulfate polysaccharides are negatively charged glycosaminoglycans and play important roles in cell-to-matrix and cell-to-cell signaling processes. Metal ion binding to heparins alters the conformation of heparins and influences their function. Various experimental techniques have been used to investigate metal ion-heparin interactions, frequently with inconsistent results. Exploiting the quadrupolar 23Na nucleus, we herein develop a 23Na NMR-based competition assay and monitor the binding of divalent Ca2+ and Mg2+ and trivalent Al3+ metal ions to sodium heparin and the consequent release of sodium ions from heparin. The 23Na spin relaxation rates and translational diffusion coefficients are utilized to quantify the metal ion-induced release of sodium ions from heparin. In the case of the Al3+ ion, the complementary approach of 27Al quadrupolar NMR is employed as a direct probe of ion binding to heparin. Our NMR results demonstrate at least two metal ion-binding sites with different affinities on heparin, potentially undergoing dynamic exchange. For the site with lower metal ion binding affinity, the order of Ca2+ > Mg2+ > Al3+ is obtained, in which even the weakly binding Al3+ ion is capable of displacing sodium ions from heparin. Overall, the multinuclear quadrupolar NMR approach employed here can monitor and quantify metal ion binding to heparin and capture different modes of metal ion-heparin binding.

Cover Feature: Harnessing Water to Enhance Quadrupolar NMR Spectroscopy and Imaging (Chem. Eur. J. 58/2022)

17O and 14N are attractive targets for in vivo NMR spectroscopy and imaging, but low gyromagnetic ratios and fast spin relaxation complicate their observations. In their Research Article (DOI: 10.1002/chem.202201490), R. P. Martinho and L. Frydman explore indirect ways for detecting these sites with the help of proton detection, amplified by chemical exchanges with the abundant water 1H signal. These amplifications are mediated by spontaneous exchanges that the labile 1Hs bound to 17O or 14N undergo with the water protons, opening new avenues in spectroscopic MRI.

Harnessing Water to Enhance Quadrupolar NMR Spectroscopy and Imaging.

17 O and 14 N are attractive targets for in vivo NMR spectroscopy and imaging, but low gyromagnetic ratios γ and fast spin relaxation complicate observations. This work explores indirect ways of detecting some of these sites with the help of proton-detected double resonance techniques. As standard coherence transfer methods are of limited use for such indirect detection, alternative routes for probing the quadrupolar spectra on 1 H were tested. These centered on modulating the broadening effects imparted onto protons adjacent to the low-γ species through J couplings through either continuous wave or spin-echo double-resonance decoupling/recoupling sequences. As in all cases, the changes imparted by these double-resonance strategies were small due to the fast relaxation undergone by the quadrupoles, the sensitivity of these approaches was amplified by transferring their effects onto the abundant water 1 H signal. These amplifications were mediated by the spontaneous exchanges that the labile 1 Hs bound to 17 O or 14 N undergo with the water protons. In experiments designed on the basis of double-resonance spin echoes, these enhancements were imparted by looping the transverse encodings together with multiple longitudinal storage periods, leading to decoupling-recoupling with exchange (D-REX) sequences. In experiments designed on the basis of continuous on/off quadrupolar decoupling, these solvent exchanges were incorporated into chemical-exchange saturation transfer schemes, leading to decoupling-recoupling with saturation transfer (D-REST) sequences. Both of these variants harnessed sizable proportions of the easily detectable water signals, in order to characterize the NMR spectra and/or to image with atomic-site specificity the 17 O and 14 N species.

Analysis and information content of quadrupolar NMR in glasses: 25Mg NMR in vitreous MgSiO3 and CaMgSi2O6

The static wideline and high-resolution magic angle spinning (MAS) 25Mg NMR lineshapes measured for isotopically enriched enstatite and diopside glasses indicate a wide distribution of the electric-field gradient (EFG) components at the 25Mg position caused by disorder. The correct characterization of this distribution requires simulations with special attention paid to the experimental parameters. Here, both the static spectra obtained by wideband excitation and the MAS-NMR spectra obtained via rotor-synchronized Hahn spin echo acquisition were successfully simulated with the Czjzek distribution model, using one consistent set of parameters. Average nuclear electric quadrupole coupling constants near 8 MHz and a distribution width around 4 MHz were obtained for both materials, which suggests that earlier results on these glasses need to be re-examined. The results of this study outline a general strategy for characterizing the local environments of strongly coupled quadrupolar nuclei in amorphous and glassy materials. Despite the discrepancies between the interaction parameters extracted from our data and those published in earlier NMR work, the best fit to the data indicate an average isotropic chemical shift near 13 ppm (vs. aqueous MgCl2 solution) for both the enstatite and diopside glasses. Assuming the applicability of the current database relating the 25Mg chemical shifts with coordination numbers in crystalline compounds, this value suggests that the Mg2+ ions are six-coordinated. This conclusion, however, is based on the simplifying assumption that the 25Mg spectrum comprises a Czjzek distribution centered at a single isotropic chemical shift value and stands in contrast to the results of recent isotope-selective neutron diffraction studies which give an average Mg-O coordination number of 4.4–4.5 for both glasses. However, reasonable fits to the MAS-NMR spectra can also be obtained when constraining the average isotropic chemical shift to 50 ppm, a value typical of four-coordinated Mg. We conclude that multiple Mg sites with different coordination numbers may well be present and that, in the present glasses, 25Mg NMR at typically used spinning rates and magnetic field strengths (20 kHz, 14.1 T) is not capable of resolving them due to excessive broadening by quadrupolar interactions.

Accurate detection of perchlorate in epoxy resins via chlorine-35 quantitative quadrupolar NMR (qQNMR).

A qQNMR methodology using chlorine-35 as the employed quadrupolar nucleus has been introduced for the first time as a robust and validated method to determine and quantify perchlorate in epoxy resins. The quantification has been carried out by using a calibration curve of lithium perchlorate. The method was validated at seven concentration levels in the range of 0.16 to 2.0 mg mL-1 (1.6 to 20 mM in perchlorate), affording intra- and inter-day accuracies lower than 0.66% (expressed in CV), robustness towards pH, temperature, resin concentration and recycle delay, a limit of detection (LOD) of 0.08 mg mL-1 (0.8 mM in perchlorate), a limit of quantification (LOQ) of 0.16 mg mL-1 (1.6 mM in perchlorate) and probably most important in such applications, having no matrix effect. The method was applied on epoxy resins containing three different types of perchlorate precursors (lithium, potassium and tetramethylammonium), affording excellent quantifications with relative errors below 2.3% compared to the spiked concentrations.

Quantitative Quadrupolar NMR (qQNMR) via nitrogen-14 for the accurate control of L-carnitine in food supplements

A qQNMR methodology using nitrogen-14 as the quadrupolar nucleus of choice has been introduced for the first time as a robust and validated method to determine and quantify L-carnitine in food supplements. The quantification has been carried out by the alternative use of a calibration curve or by addition of ammonium chloride as internal standard. The method was validated at seven concentration levels in the range of 5.58–99.26 mM, affording intra- and inter day accuracies lower than 6.84% (expressed in CV), robustness towards temperature and recycle delay, limit of detection (LOD) of 2.48 mM, limit of quantification (LOQ) of 5.58 mM and remarkably with absence of matrix effect.

Recent developments in deuterium solid-state NMR for the detection of slow motions in proteins

Slow timescale dynamics in proteins are essential for a variety of biological functions spanning ligand binding, enzymatic catalysis, protein folding and misfolding regulations, as well as protein–protein and protein–nucleic acid interactions. In this review, we focus on the experimental and theoretical developments of 2H static NMR methods applicable for studies of microsecond to millisecond motional modes in proteins, particularly rotating frame relaxation dispersion (R1ρ), quadrupolar Carr–Purcell–Meiboom–Gill (QCPMG) relaxation dispersion, and quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST). With applications chosen from amyloid-β fibrils, we show the complementarity of these approaches for elucidating the complexities of conformational ensembles in disordered domains in the non-crystalline solid state, with the employment of selective deuterium labels. Combined with recent advances in relaxation dispersion backbone measurements for 15N/13C/1H nuclei, these techniques provide powerful tools for studies of biologically relevant timescale dynamics in disordered domains in the solid state.

A Practical Review of NMR Lineshapes for Spin-1/2 and Quadrupolar Nuclei in Disordered Materials.

NMR is a powerful spectroscopic method that can provide information on the structural disorder in solids, complementing scattering and diffraction techniques. The structural disorder in solids can generate a dispersion of local magnetic and electric fields, resulting in a distribution of isotropic chemical shift δiso and quadrupolar coupling CQ. For spin-1/2 nuclei, the NMR linewidth and shape under high-resolution magic-angle spinning (MAS) reflects the distributions of isotropic chemical shift, providing a rich source of disorder information. For quadrupolar nuclei, the second-order quadrupolar broadening remains present even under MAS. In addition to isotropic chemical shift, structural disorder can impact the electric field gradient (EFG) and consequently the quadrupolar NMR parameters. The distributions of quadrupolar coupling and isotropic chemical shift are superimposed with the second-order quadrupolar broadening, but can be potentially characterized by MQMAS (multiple-quantum magic-angle spinning) spectroscopy. We review analyses of NMR lineshapes in 2D DQ–SQ (double-quantum single-quantum) and MQMAS spectroscopies, to provide a guide for more general lineshape analysis. In addition, methods to enhance the spectral resolution and sensitivity for quadrupolar nuclei are discussed, including NMR pulse techniques and the application of high magnetic fields. The role of magnetic field strength and its impact on the strategy of determining optimum NMR methods for disorder characterization are also discussed.

Quadrupolar NMR Relaxation of Aqueous 127I-, 131Xe, and 133Cs+: A First-Principles Approach from Dynamics to Properties.

Quadrupolar NMR relaxation rates were computed for aqueous 133Cs+, 131Xe, and 127I- via Kohn-Sham (KS) density functional theory-based ab initio molecular dynamics and KS calculations of the electric field gradient (EFG) tensors along the trajectories. The resulting rates are within a factor of 1-3 of the experimental values and can be compared to available results from classical dynamics and EFGs from electrostatic models with corrections via Sternheimer antishielding factors. Relativistic effects are shown to have an enhancing effect on the magnitude of the EFGs. An analysis of the EFGs was carried out in terms of localized molecular orbitals to elucidate contributions from the solvent versus solute polarization and assess the validity of the Sternheimer approximation for these systems.

Estimation of solid-liquid interfacial potential enabled by quantitative analysis and relaxation observation of quadrupolar NMR

Relaxation time measurements and quantitative analyses of quadrupolar nuclei via NMR were effective for the estimation of the interfacial potential at the solid-liquid interface. Moreover, quantitative nuclear magnetic resonance (qNMR) spectroscopy experiments for 23Na and 35Cl nuclei were performed. The calibration curve of the external standard aqueous NaCl solution showed excellent linearity over a considerably wide concentration range from 4 × 10−4 to 2 mol L−1 (an increase in concentration of 5000 times), with a simple experimental and analytical procedure. The relaxation time and detection rate of Cl– ions in the 35Cl NMR spectrum of a 0.10 mol L–1 NaCl aq. solution with 10 vol% α-Al2O3 drastically decreased as the zeta potential of the solid phase (ζs) of α-Al2O3 approximated a negative value. Such a result was due to the decrease in both the mobility of Cl– ions and the symmetry of the electrostatic field around 35Cl nuclei caused by the electrostatic interactions between Cl– ions and the solid surface. In the case of Na+ ions, which have a charge opposite to that of Cl– ions, the ζs dependences of the relaxation time and detection rate of Na+ ions of 23Na NMR were also opposite to those of 35Cl NMR. Particularly, such values were almost constant when ζs > 0 mV but decreased monotonically when ζs < 0 mV. It was also clarified that the counterions condensed around the vicinity of the solid phase wherein the concentration of the counterions was approximately several tens of times higher than that in the bulk phase. The estimation of electrostatic field intensities not only at solid-liquid interfaces but also at liquid-liquid interfaces and various interfaces, including those in non-aqueous solvents, can thus be performed through the proposed method.

Enhanced Rotation by Ground State Destabilization in Amphidynamic Crystals of a Dipolar 2,3-Difluorophenylene Rotator as Established by Solid State 2H NMR and Dielectric Spectroscopy

We report the synthesis and rotational dynamics of the pillared metal–organic framework Zn2(F2BDC)2(DABCO) where F2BDC = 2,3-difluorobenzene-1,4-dicarboxylate acts as a rotating dipolar linker and DABCO = 1,4-diazabicyclo[2.2.2]octane acts as a spacer (F2MOF 1). The pillared structure of F2MOF 1 was confirmed by X-ray diffraction and CP-MAS 13C NMR analyses. Using variable temperature solid state 2H NMR and broadband dielectric spectroscopy, we characterized the rotational dynamics of the dipolar F2BDC linker in the solid state. Variable temperature (VT) quadrupolar echo 2H NMR measurements revealed a rotational activation energy of Ea = 6.8 ± 0.1 kcal/mol, which agreed well with temperature- and frequency-dependent dielectric measurements, indicating a barrier of Ea = 7.1 ± 0.5 kcal/mol. Structural data from single crystal X-ray diffraction and quantum mechanical calculations (DFT) suggest that the rotational potential is determined by steric interactions between the dipolar rotator and the stator linkers such that fluorine atoms in the F2BDC linker reduce the activation energy by destabilization of the coplanar BDC ground state.

Deuteron Quadrupolar Chemical Exchange Saturation Transfer (Q-CEST) Solid-State NMR for Static Powder Samples: Approach and Applications to Amyloid-β Fibrils.

We provide an experimental and computational framework for 2 H quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST) under static solid-state conditions for the quantification of dynamics on μs-ms timescales. Simulations using simple 2-site exchange models provide insights into the relation between spin dynamics and motions. Biological applications focus on two sites of amyloid-β fibrils in the 3-fold symmetric polymorph. The first site, the methyl group of A2 of the disordered N-terminal domain, undergoes diffusive motions and conformational exchange due to transient interactions. Earlier 2 H rotating frame relaxation and quadrupolar CPMG measurements are combined with the Q-CEST approach to characterize the multiple conformational states of the domain. The second site, the methyl group of M35, spans the water-accessible cavity inside the fibrils' core and undergoes extensive rotameric exchange. Q-CEST permits us to refine the rotameric exchange model for this site and allows the more precise determination of populations and rotameric exchange rate constants than line shape analysis.

Fluorescence and Rotational Dynamics of a Crystalline Molecular Rotor Featuring an Aggregation-Induced Emission Fluorophore.

Recent studies have shown that "crystal fluidity" in the form of fast conformational motions is critical for large-amplitude rotational motion in crystals. To explore this concept, we designed a crystalline assembly featuring two diethynylbenzene (DEB) molecular rotators linked to tetraphenylethylene (TPE), a fluorophore known to emit with intensities that depend on the rigidity of the medium. We envisioned that an increase in crystal fluidity as a function of increasing temperature would facilitate rotational motion of the DEB while diminishing the fluorescence intensity of the TPE. The aggregation-induced emission of the TPE moiety was confirmed when its fluorescence intensity increased by the addition of water to a THF solution. While bulk solids showed a relatively strong TPE emission with a lifetime of 4 ± 1 ns, no significant changes were observed between measurements carried out from 77 to 298 K, indicating that the crystal environment has limited motion within the excited-state lifetime. This conclusion was confirmed by the quadrupolar echo 2H NMR line-shape analysis of a deuterium-labeled sample between 198 and 298 K, which revealed rotational correlation times in the microsecond regime, suggesting that rotational fluidity is 3 orders of magnitude too slow to affect fluorescence emission.

First-Order Metal–Semiconductor Transition Triggered by Rattling Transition in Tetrahedrite Cu12Sb4S13: Cu-Nuclear Magnetic Resonance Studies

Tetrahedrite Cu12Sb4S13 shows a metal–semiconductor transition (MST) at TMST = 85 K. We have studied the mechanism of the MST by measurements of Cu-NMR. Above TMST, the Cu-NMR spectrum consists of signals from a tetrahedral Cu(1) 12d site and a trigonally coordinated Cu(2) 12e site. Analyses of the spectra at 95 and 20 K yield NMR and nuclear quadrupole resonance (NQR) parameters above and below TMST. The Cu(1) signal does not show clear quadrupole splitting, which remains unchanged on cooling across TMST. On the other hand, the Cu(2) signal at T > TMST clearly shows the quadrupole splitting characterized by a quadrupole frequency νQ(2) ≈ 18.6 MHz and an asymmetry parameter η(2) ≈ 0.03. Below TMST, the values of νQ(2) and η(2) change markedly. Such marked changes in NQR parameters provide evidence of a remarkable change in the local electronic structure around the Cu(2) site. Together with νQ from NMR spectra and that from first-principles calculation, we conclude that the Cu(2) atoms are displaced from the sulfur triangles below TMST. We also found that the NMR Knight shift and the spin–lattice relaxation rate divided by temperature, 1/T1T, for the Cu(1) signal markedly change below TMST, which is ascribable to the reduction in the electronic density of states at the Fermi level. We further discuss the relationship among the MST, structural transformation, and crystal structure below TMST.