Delving into theoretical and computational considerations for accurate calculation of chemical shifts in paramagnetic transition metal systems using quantum chemical methods.

The chemical shielding tensor for a paramagnetic system has been derived from the macroscopically observed magnetization using the perturbation theory. An approach to calculate the paramagnetic chemical shifts in transition metal systems based on the spin-only magnetic susceptibility directly evaluated from the ab initio Hilbert space of the electronic Zeeman Hamiltonian has been discussed. Computationally, several advantages are associated with this approach: (a) it includes the state-specific paramagnetic Curie (first-order) and Van Vleck (second-order) contributions of the paramagnetic ion to the paramagnetic chemical shifts; (b) thus it avoids the system-specific modeling and evaluating effectively in terms of the electron paramagnetic resonance (EPR) spin Hamiltonian parameters of the magnetic moment of the paramagnetic ion formulated previously; (c) it can be utilized both in the point-dipole (PD) approximation (in the long-range) and with the quantum chemical (QC) method based the hyperfine tensors (in the short-range). Additionally, we have examined the predictive performance of various density functional theory (DFT) functionals of different families and commonly used core-augmented basis sets for nuclear magnetic resonance (NMR) chemical shifts. A selection of transition metal ion complexes with and without first-order orbital contributions, namely the [M(AcPyOx)3(BPh)]+ complexes of M = Mn2+, Ni2+ and Co2+ ions and CoTp2 complex and their reported NMR chemical shifts are studied from QC methods for illustration.

Geometry and electronic structure of Yb(III)[CH(SiMe3)2]3 from EPR and solid-state NMR augmented by computations.

Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)[CH(SiMe3)2]3, a prototypical example, which contains notable structural features according to X-ray crystallography. Each of these techniques revealed specific information about the geometry and electronic structure of the complex. Taken together, both EPR and NMR, augmented by quantum chemical calculations, provide a detailed and complementary understanding of such paramagnetic compounds. In particular, the EPR and NMR signatures point to the presence of three-centre-two-electron Yb-γ-Me-ß-Si secondary metal-ligand interactions in this otherwise tri-coordinate metal complex, similarly to its diamagnetic Lu analogues. The electronic structure of Yb(III) can be described as a single 4f13 configuration, while an unusually large crystal-field splitting results in a thermally isolated ground Kramers doublet. Furthermore, the computational data indicate that the Yb-carbon bond contains some π-character, reminiscent of the so-called α-H agostic interaction.

Structure Determination and Refinement of Paramagnetic Materials by Solid-State NMR.

Paramagnetism in solid-state materials has long been considered an additional challenge for structural investigations by using solid-state nuclear magnetic resonance spectroscopy (ssNMR). The strong interactions between unpaired electrons and the surrounding atomic nuclei, on the one hand, are complex to describe, and on the other hand can cause fast decaying signals and extremely broad resonances. However, significant progress has been made over the recent years in developing both theoretical models to understand and calculate the frequency shifts due to paramagnetism and also more sophisticated experimental protocols for obtaining high-resolution ssNMR spectra. While the field is continuously moving forward, to date, the combination of state-of-the-art numerical and experimental techniques enables us to obtain high-quality data for a variety of systems. This involves the determination of several ssNMR parameters that represent different contributions to the frequency shift in paramagnetic solids. These contributions encode structural information on the studied material on various length scales, ranging from crystal morphologies, to the mid- and long-range order, down to the local atomic bonding environment. In this perspective, the different ssNMR parameters characteristic for paramagnetic materials are discussed with a focus on their interpretation in terms of structure. This includes a summary of studies that have explored the information content of these ssNMR parameters, mostly to complement experimental data from other methods, e.g., X-ray diffraction. The presented overview aims to demonstrate how far ssNMR has hitherto been able to determine and refine the structures of materials and to discuss where it currently falls short of its full potential. We attempt to highlight how much further ssNMR can be pushed to determine and refine structure to deliver a comprehensive structural characterization of paramagnetic materials comparable to what is to date achieved by the combined effort of electron microscopy, diffraction, and spectroscopy.

Probing the electronic structure and hydride occupancy in barium titanium oxyhydride through DFT-assisted solid-state NMR.

Perovskite-type oxhydrides such as BaTiO3-xHy exhibit mixed hydride ion and electron conduction and are an attractive class of materials for developing energy storage devices. However, the underlying mechanism of electric conductivity and its relation to the composition of the material remains unclear. Here we report detailed insights into the hydride local environment, the electronic structure and hydride conduction dynamics of barium titanium oxyhydride. We demonstrate that DFT-assisted solid-state NMR is an excellent tool for differentiating between the different feasible electronic structures in these solids. Our results indicate that upon reduction of BaTiO3 the introduced electrons are delocalized among all Ti atoms forming a bandstate. Furthermore, each vacated anion site is reoccupied by at most a single hydride, or else remains vacant. This single occupied bandstate structure persists at different hydrogen concentrations (y = 0.13-0.31) and a wide range of temperatures (∼100-300 K).

Half-integer-spin quadrupolar nuclei in magic-angle spinning paramagnetic NMR: The case of NaMnO2.

A combination of solid-state NMR methods for the extraction of 23Na shift and quadrupolar parameters in the as-synthesized, structurally complex NaMnO2 Na-ion cathode material, under magic-angle spinning (MAS) is presented. We show that the integration of the Magic-Angle Turning experiment with Rotor-Assisted Population transfer (RAPT) can be used both to identify shifts and to extract a range of magnitudes for their quadrupolar couplings. We also demonstrate the applicability of the two-dimensional one pulse (TOP) based double-sheared Satellite Transition Magic-Angle Spinning (TOP-STMAS) showing how it can yield a spectrum with separated shift and second-order quadrupolar anisotropies, which in turn can be used to analyze a quadrupolar lineshape free of anisotropic bulk magnetic susceptibility (ABMS) induced shift dispersion and determine both isotropic shift and quadrupolar products. Combining all these experiments, the shift and quadrupolar parameters for all observed Na environments were extracted and yielded excellent agreement with the density functional theory (DFT) based models that were reported in previous literature. We expect these methods to open the door for new possibilities for solid-state NMR to probe half-integer quadrupolar nuclei in paramagnetic materials and other systems exhibiting large shift dispersion.

1H-Detected Biomolecular NMR under Fast Magic-Angle Spinning.

Since the first pioneering studies on small deuterated peptides dating more than 20 years ago, 1H detection has evolved into the most efficient approach for investigation of biomolecular structure, dynamics, and interactions by solid-state NMR. The development of faster and faster magic-angle spinning (MAS) rates (up to 150 kHz today) at ultrahigh magnetic fields has triggered a real revolution in the field. This new spinning regime reduces the 1H-1H dipolar couplings, so that a direct detection of 1H signals, for long impossible without proton dilution, has become possible at high resolution. The switch from the traditional MAS NMR approaches with 13C and 15N detection to 1H boosts the signal by more than an order of magnitude, accelerating the site-specific analysis and opening the way to more complex immobilized biological systems of higher molecular weight and available in limited amounts. This paper reviews the concepts underlying this recent leap forward in sensitivity and resolution, presents a detailed description of the experimental aspects of acquisition of multidimensional correlation spectra with fast MAS, and summarizes the most successful strategies for the assignment of the resonances and for the elucidation of protein structure and conformational dynamics. It finally outlines the many examples where 1H-detected MAS NMR has contributed to the detailed characterization of a variety of crystalline and noncrystalline biomolecular targets involved in biological processes ranging from catalysis through drug binding, viral infectivity, amyloid fibril formation, to transport across lipid membranes.

Separation of quadrupolar and paramagnetic shift interactions in high-resolution nuclear magnetic resonance of spinning powders.

Separation and correlation of the shift anisotropy and the first-order quadrupolar interaction of spin I = 1 nuclei under magic-angle spinning (MAS) are achieved by the phase-adjusted spinning sideband (PASS) nuclear magnetic resonance (NMR) experiment. Compared to methods for static samples, this approach has the benefit of higher sensitivity and resolution. Moreover, the PASS experiment has the advantage over previous MAS sequences in the ability to completely separate the shift anisotropy and first-order quadrupolar interactions. However, the main drawback of the pulse sequence is the lower excitation bandwidth. The sequence is comprehensively evaluated using theoretical calculations and numerical simulations and applied experimentally to the 2H NMR of a range of paramagnetic systems: deuterated nickel(II) acetate tetrahydrate, deuterated copper(II) chloride dihydrate, and two forms of deuterated oxyhydride ion conductor BaTiO3-xHy. Our results show that despite the issue with broadband excitation, the extracted shift and quadrupolar interaction tensors and the Euler angles relating the two tensors match well with the NMR parameters obtained with static NMR methods. Therefore, the new application of the PASS experiment is an excellent addition to the arsenal of NMR experiments for 2H and potentially 14N in paramagnetic solids.

Crystal and electronic facet analysis of ultrafine Ni2P particles by solid-state NMR nanocrystallography.

Structural and morphological control of crystalline nanoparticles is crucial in the field of heterogeneous catalysis and the development of "reaction specific" catalysts. To achieve this, colloidal chemistry methods are combined with ab initio calculations in order to define the reaction parameters, which drive chemical reactions to the desired crystal nucleation and growth path. Key in this procedure is the experimental verification of the predicted crystal facets and their corresponding electronic structure, which in case of nanostructured materials becomes extremely difficult. Here, by employing 31P solid-state nuclear magnetic resonance aided by advanced density functional theory calculations to obtain and assign the Knight shifts, we succeed in determining the crystal and electronic structure of the terminating surfaces of ultrafine Ni2P nanoparticles at atomic scale resolution. Our work highlights the potential of ssNMR nanocrystallography as a unique tool in the emerging field of facet-engineered nanocatalysts.

Indium(III) in the "Periodic Table" of Di(2-pyridyl) Ketone: An Unprecedented Transformation of the Ligand and Solid-State 115In NMR Spectroscopy as a Valuable Structural Tool.

Reactions of di(2-pyridyl) ketone, (py)2CO, with indium(III) halides in CH3NO2 have been studied, and a new transformation of the ligand has been revealed. In the presence of InIII, the C═O bond of (py)2CO is subjected to nucleophilic attack by the carbanion -:CH2NO2, yielding the dinuclear complexes [In2X4{(py)2C(CH2NO2)(O)}2] (X = Cl, 1; X = Br, 2; X = I, 3) in moderate to good yields. The alkoxo oxygens of the two η1:η2:η1-(py)2C(CH2NO2)(O)- ligands doubly bridge the InIII centers and create a {In2(µ2-OR)2}4+ core. Two pyridyl nitrogens of different organic ligands and two terminal halogeno ions complete a distorted-octahedral stereochemistry around each In(III) ion. After maximum excitation at 360 or 380 nm, the solid chloro complex 1 emits blue light at 420 and 440 nm at room temperature, the emission being attributed to charge transfer within the coordinated organic ligand. Solid-state 115In NMR spectra, in combination with DFT calculations, of 1-3 have been studied in detail at both 9.4 and 14.1 T magnetic fields. The nuclear quadrupolar and chemical shift parameters provide valuable findings concerning the electric field gradients and magnetic shielding at the nuclei of indium, respectively. The experimentally derived CQ values are 40 ± 3 MHz for 1, 46 ± 5 MHz for 2, and 50 ± 10 and 64 ± 7 MHz for the two crystallographically independent InIII sites for 3, while the δiso values fall in the range 130 ± 30 to -290 ± 60 ppm. The calculated CQ and asymmetry parameter (ηQ) values are fully consistent with the experimental values for 1 and 2 and are in fairly good agreement for 3. The results have been analyzed and discussed in terms of the known (1, 3) and proposed (2) structural features of the complexes, demonstrating that 115In NMR is an effective solid-state technique for the study of indium(III) complexes.

A method to calculate the NMR spectra of paramagnetic species using thermalized electronic relaxation.

For paramagnetic species, it has been long understood that the hyperfine interaction between the unpaired electrons and the nucleus results in a nuclear magnetic resonance (NMR) peak that is shifted by a paramagnetic shift, rather than split by the coupling, due to an averaging of the electronic magnetic moment caused by electronic relaxation that is fast in comparison to the hyperfine coupling constant. However, although this feature of paramagnetic NMR has formed the basis of all theories of the paramagnetic shift, the precise theory and mechanism of the electronic relaxation required to predict this result has never been discussed, nor has the assertion been tested. In this paper, we show that the standard semi-classical Redfield theory of relaxation fails to predict a paramagnetic shift, as does any attempt to correct for the semi-classical theory using modifications such as the inhomogeneous master equation or Levitt-di Bari thermalization. In fact, only the recently-introduced Lindbladian theory of relaxation in magnetic resonance [J.Magn.Reson., 310, 106645 (2019)] is able to correctly predict the paramagnetic shift tensor and relaxation-induced linewidth in pNMR. Furthermore, this new formalism is able to predict the NMR spectra of paramagnetic species outside the high-temperature and weak-order limits, and is therefore also applicable to dynamic nuclear polarization. The formalism is tested by simulations of five case studies, which include Fermi-contact and spin-dipolar hyperfine couplings, g-anisotropy, zero-field splitting, high and low temperatures, and fast and slow electronic relaxation.

Frequency-swept adiabatic pulses for broadband solid-state MAS NMR.

We present a complete description of frequency-swept adiabatic pulses applied to isolated spin-1/2 nuclei with a shift anisotropy in solid materials under magic-angle spinning. Our theoretical framework unifies the existing descriptions of adiabatic pulses in the high-power regime, where the radiofrequency (RF) amplitude is greater than twice the spinning frequency, and the low-power regime, where the RF power is less than the spinning frequency, and so links the short high-powered adiabatic pulse (SHAP) and single-sideband-selective adiabatic pulses (S3AP) schemes used in paramagnetic solid-state NMR. We also identify a hitherto unidentified third regime intermediate between the low- and high-power regimes, and separated from them by rotary resonance conditions. We show that the prevailing benchmark of inversion performance based on (super) adiabatic factors is only applicable in the high- and intermediate-power regimes, but fails to account both for the poor performance at rotary resonance, and the impressive inversion seen in the low-power regime. For low-power pulses, which are non-adiabatic according to this definition of (super) adiabaticity, the effective Floquet Hamiltonian in the jolting frame reveals "hidden" (super) adiabaticity. The theory is demonstrated using a combination of simulation and experiment, and is used to refine the practical recommendations for the experimentalist who wishes to use these pulses.

Proton-detected fast-magic-angle spinning NMR of paramagnetic inorganic solids.

Fast (60 kHz) magic angle spinning solid-state NMR allows very sensitive proton detection in highly paramagnetic organometallic powders. We showcase this technique with the complete assignment of 1H and 13C resonances in a high-spin Fe(ii) polymerisation catalyst with less than 2 mg of sample at natural abundance.

Low-power synchronous helical pulse sequences for large anisotropic interactions in MAS NMR: Double-quantum excitation of 14N.

We develop a theoretical framework for a class of pulse sequences in the nuclear magnetic resonance (NMR) of rotating solids, which are applicable to nuclear spins with anisotropic interactions substantially larger than the spinning frequency, under conditions where the radiofrequency amplitude is smaller than or comparable to the spinning frequency. The treatment is based on average Hamiltonian theory and allows us to derive pulse sequences with well-defined relationships between the pulse parameters and spinning frequency for exciting specific coherences without the need for any detailed calculations. This framework is applied to the excitation of double-quantum spectra of 14N and is used both to evaluate the existing low-power pulse schemes and to predict the new ones, which we present here. It is shown that these sequences can be designed to be γ-encoded and therefore allow the acquisition of sideband-free spectra. It is also shown how these new double-quantum excitation sequences are incorporated into heteronuclear correlation NMR, such as 1H-14N dipolar double-quantum heteronuclear multiple-quantum correlation spectroscopy. The new experiments are evaluated both with numerical simulations and experiments on glycine and N-acetylvaline, which represent cases with "moderate" and "large" quadrupolar interactions, respectively. The analyzed pulse sequences perform well for the case of a "moderate" quadrupolar interaction, however poorly with a "large" quadrupolar interaction, for which future work on pulse sequence development is necessary.

Picometer Resolution Structure of the Coordination Sphere in the Metal-Binding Site in a Metalloprotein by NMR.

Most of our understanding of chemistry derives from atomic-level structures obtained with single-crystal X-ray diffraction. Metal centers in X-ray structures of small organometallic or coordination complexes are often extremely well-defined, with errors in the positions on the order of 10-4-10-5 Å. Determining the metal coordination geometry to high accuracy is essential for understanding metal center reactivity, as even small structural changes can dramatically alter the metal activity. In contrast, the resolution of X-ray structures in proteins is limited typically to the order of 10-1 Å. This resolution is often not sufficient to develop precise structure-activity relations for the metal sites in proteins, because the uncertainty in positions can cover all of the known ranges of bond lengths and bond angles for a given type of metal complex. Here we introduce a new approach that enables the determination of a high-definition structure of the active site of a metalloprotein from a powder sample, by combining magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, tailored radio frequency (RF) irradiation schemes, and computational approaches. This allows us to overcome the "blind sphere" in paramagnetic proteins, and to observe and assign 1H, 13C, and 15N resonances for the ligands directly coordinating the metal center. We illustrate the method by determining the bond lengths in the structure of the CoII coordination sphere at the core of human superoxide dismutase 1 (SOD) with 0.7 pm precision. The coordination geometry of the resulting structure explains the nonreactive nature of the CoII/ZnII centers in these proteins, which allows them to play a purely structural role.

Resolving Dirac electrons with broadband high-resolution NMR.

Detecting the metallic Dirac electronic states on the surface of Topological Insulators (TIs) is critical for the study of important surface quantum properties (SQPs), such as Majorana zero modes, where simultaneous probing of the bulk and edge electron states is required. However, there is a particular shortage of experimental methods, showing at atomic resolution how Dirac electrons extend and interact with the bulk interior of nanoscaled TI systems. Herein, by applying advanced broadband solid-state 125Te nuclear magnetic resonance (NMR) methods on Bi2Te3 nanoplatelets, we succeeded in uncovering the hitherto invisible NMR signals with magnetic shielding that is influenced by the Dirac electrons, and we subsequently showed how the Dirac electrons spread inside the nanoplatelets. In this way, the spin and orbital magnetic susceptibilities induced by the bulk and edge electron states were simultaneously measured at atomic scale resolution, providing a pertinent experimental approach in the study of SQPs.

Separation of quadrupolar and paramagnetic shift interactions with TOP-STMAS/MQMAS in solid-state lighting phosphors.

A new approach for processing satellite-transition magic-angle spinning (STMAS) and multiple-quantum magic-angle spinning (MQMAS) data, based on the two-dimensional one-pulse (TOP) method, which separates the second-rank quadrupolar anisotropy and paramagnetic shift interactions via a double shearing transformation, is described. This method is particularly relevant in paramagnetic systems, where substantial inhomogeneous broadening may broaden the lineshapes. Furthermore, it possesses an advantage over the conventional processing of MQMAS and STMAS spectra because it overcomes the limitation on the spectral width in the indirect dimension imposed by rotor synchronization of the sampling interval. This method was applied experimentally to the 27 Al solid-state nuclear magnetic resonance of a series of yttrium aluminum garnets (YAGs) doped with different lanthanide ions, from which the quadrupolar parameters of paramagnetically shifted and bulk unshifted sites were extracted. These parameters were then compared with density functional theory calculations, which permitted a better understanding of the local structure of Ln substituent ions in the YAG lattice.

Mysterious SiB3: Identifying the Relation between α- and ß-SiB3.

Binary silicon boride SiB3 has been reported to occur in two forms, as disordered and nonstoichiometric α-SiB3-x , which relates to the α-rhombohedral phase of boron, and as strictly ordered and stoichiometric ß-SiB3. Similar to other boron-rich icosahedral solids, these SiB3 phases represent potentially interesting refractory materials. However, their thermal stability, formation conditions, and thermodynamic relation are poorly understood. Here, we map the formation conditions of α-SiB3-x and ß-SiB3 and analyze their relative thermodynamic stabilities. α-SiB3-x is metastable (with respect to ß-SiB3 and Si), and its formation is kinetically driven. Pure polycrystalline bulk samples may be obtained within hours when heating stoichiometric mixtures of elemental silicon and boron at temperatures 1200-1300 °C. At the same time, α-SiB3-x decomposes into SiB6 and Si, and optimum time-temperature synthesis conditions represent a trade-off between rates of formation and decomposition. The formation of stable ß-SiB3 was observed after prolonged treatment (days to weeks) of elemental mixtures with ratios Si/B = 1:1-1:4 at temperatures 1175-1200 °C. The application of high pressures greatly improves the kinetics of SiB3 formation and allows decoupling of SiB3 formation from decomposition. Quantitative formation of ß-SiB3 was seen at 1100 °C for samples pressurized to 5.5-8 GPa. ß-SiB3 decomposes peritectoidally at temperatures between 1250 and 1300 °C. The highly ordered nature of ß-SiB3 is reflected in its Raman spectrum, which features narrow and distinct lines. In contrast, the Raman spectrum of α-SiB3-x is characterized by broad bands, which show a clear relation to the vibrational modes of isostructural, ordered B6P. The detailed composition and structural properties of disordered α-SiB3-x were ascertained by a combination of single-crystal X-ray diffraction and 29Si magic angle spinning NMR experiments. Notably, the compositions of polycrystalline bulk samples (obtained at T ≤ 1200 °C) and single crystal samples (obtained from Si-rich molten Si-B mixtures at T > 1400 °C) are different, SiB2.93(7) and SiB2.64(2), respectively. The incorporation of Si in the polar position of B12 icosahedra results in highly strained cluster units. This disorder feature was accounted for in the refined crystal structure model by splitting the polar position into three sites. The electron-precise composition of α-SiB3-x is SiB2.5 and corresponds to the incorporation of, on average, two Si atoms in each B12 icosahedron. Accordingly, α-SiB3-x constitutes a mixture of B10Si2 and B11Si clusters. The structural and phase stability of α-SiB3-x were explored using a first-principles cluster expansion. The most stable composition at 0 K is SiB2.5, which however is unstable with respect to the decomposition ß-SiB3 + Si. Modeling of the configurational and vibrational entropies suggests that α-SiB3-x only becomes more stable than ß-SiB3 at temperatures above its decomposition into SiB6 and Si. Hence, we conclude that α-SiB3-x is metastable at all temperatures. Density functional theory electronic structure calculations yield band gaps of similar size for electron-precise α-SiB2.5 and ß-SiB3, whereas α-SiB3 represents a p-type conductor.

Insights into the Exfoliation Process of V2O5·nH2O Nanosheet Formation Using Real-Time 51V NMR.

Nanostructured hydrated vanadium oxides (V2O5·nH2O) are actively being researched for applications in energy storage, catalysis, and gas sensors. Recently, a one-step exfoliation technique for fabricating V2O5·nH2O nanosheets in aqueous media was reported; however, the underlying mechanism of exfoliation has been challenging to study. Herein, we followed the synthesis of V2O5·nH2O nanosheets from the V2O5 and VO2 precursors in real time using solution- and solid-state 51V NMR. Solution-state 51V NMR showed that the aqueous solution contained mostly the decavanadate anion [H2V10O28]4- and the hydrated dioxovanadate cation [VO2·4H2O]+, and during the exfoliation process, decavanadate was formed, while the amount of [VO2·4H2O]+ remained constant. The conversion of the solid precursor V2O5, which was monitored with solid-state 51V NMR, was initiated when VO2 was in its monoclinic forms. The dried V2O5·nH2O nanosheets were weakly paramagnetic because of a minor content of isolated V4+. Its solid-state 51V signal was less than 20% of V2O5 and arose from diamagnetic V4+ or V5+.This study demonstrates the use of real-time NMR techniques as a powerful analysis tool for the exfoliation of bulk materials into nanosheets. A deeper understanding of this process will pave the way to tailor these important materials.

When Do Anisotropic Magnetic Susceptibilities Lead to Large NMR Shifts? Exploring Particle Shape Effects in the Battery Electrode Material LiFePO4.

Materials used as electrodes in energy storage devices have been extensively studied with solid-state NMR spectroscopy. Due to the almost ubiquitous presence of transition metals, these systems are also often magnetic. While it is well known that the presence of anisotropic bulk magnetic susceptibility (ABMS) leads to broadening of resonances under magic angle spinning, we show that for monodisperse and nonspherical particle morphologies the ABMS can also lead to considerable shifts, which vary substantially as a function of particle shape. This, on one hand, complicates the interpretation of the NMR spectrum and means that different samples of the same nominal material may no longer give rise to the same measured shift. On the other hand, the ABMS shift provides a mechanism with which to derive the particle shape from the NMR spectrum. In this work, we present a methodology to model the ABMS shift and relate it to the shape of the studied particles. The approach is tested on the 7Li NMR spectra of single crystals and powders of LiFePO4. The results show that the ABMS shift can be a major contribution to the total NMR shift in systems with large magnetic anisotropies and small hyperfine shifts, 7Li shifts for typical LiFePO4 morphologies varying by as much as 100 ppm. The results are generalized to demonstrate that the approach can be used as a means with which to probe the aspect ratio of particles. The work has implications for the analysis of NMR spectra of all materials with anisotropic magnetic susceptibilities, including diamagnetic materials such as graphite.

Observing an Antisense Drug Complex in Intact Human Cells by in-Cell NMR Spectroscopy.

Gaining insight into the uptake, trafficking and target engagement of drugs in cells can enhance understanding of a drug's function and efficiency. However, there are currently no reliable methods for studying untagged biomolecules in macromolecular complexes in intact human cells. Here we have studied an antisense oligonucleotide (ASO) drug in HEK 293T and HeLa cells by NMR spectroscopy. Using a combination of transfection, cryoprotection and dynamic nuclear polarization (DNP), we were able to detect the drug directly in intact frozen cells. Activity of the drug was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). By applying DNP NMR to frozen cells, we overcame limitations both of solution-state in-cell NMR spectroscopy (e.g., size, stability and sensitivity) and of visualization techniques, in which (e.g., fluorescent) tagging of the ASO decreases its activity. The capability to detect an untagged, active drug, interacting in its natural environment, represents a first step towards studying molecular mechanisms in intact cells.