Solid-state NMR Relaxation Research Articles

Allostery at a Protein-Protein Interface Harboring an Intermolecular Motional Network.

Motional properties of proteins govern recognition, catalysis, and regulation. The dynamics of tightly interacting residues can form intramolecular dynamic networks, dependencies fine-tuned by evolution to optimize a plethora of functional aspects. The constructive interaction of residues from different proteins to assemble intermolecular dynamic networks is a similarly likely case but has escaped thorough experimental assessment due to interfering association/dissociation dynamics. Here, we use fast-MAS solid-state 15N R1ρ NMR relaxation dispersion aided by molecular-dynamics simulations to mechanistically assess the hierarchy of individual μs timescale motions arising from a crystal-crystal contact, in the absence of translational motion. In contrast to the monomer, where particular mutations entail isolated perturbations, specific intermolecular interactions couple the motional properties between distant residues in the same protein. The mechanistic insights obtained from this conceptual work may improve our understanding on how intramolecular allostery can be tuned by intermolecular interactions via assembly of dynamic networks from previously isolated elements.

Carbon-detected deuterium solid-state NMR rotating frame relaxation measurements for protein methyl groups under magic angle spinning

Deuterium rotating frame solid-state NMR relaxation measurements (2H R1ρ) are important tools in quantitative studies of molecular dynamics. We demonstrate how 2H to 13C cross-polarization (CP) approaches under 10–40 kHz magic angle spinning rates can be combined with the 2H R1ρ blocks to allow for extension of deuterium rotating frame relaxation studies to methyl groups in biomolecules. This extension permits detection on the 13C nuclei and, hence, for the achievement of site-specific resolution. The measurements are demonstrated using a nine-residue low complexity peptide with the sequence GGKGMGFGL, in which a single selective −13CD3 label is placed at the methionine residue. Carbon-detected measurements are compared with the deuterium direct-detection results, which allows for fine-tuning of experimental approaches. In particular, we show how the adiabatic respiration CP scheme and the double adiabatic sweep on the 2H and 13C channels can be combined with the 2H R1ρ relaxation rates measurement. Off-resonance 2H R1ρ measurements are investigated in addition to the on-resonance condition, as they extent the range of effective spin-locking field.

Solid-state NMR spectroscopy uncovers internal dynamics of antiviral compounds.

In this study we analyzed the internal dynamics of antiviral compounds such as amantadine and rimantadine and the model compound hexamethylbenzene (HMB) using solid-state 2H NMR spectroscopy. Amantadine and rimantadine have been successfully used to treat influenza and dyskinesia, and their antiviral activity can be characterized using structural and dynamical information from solid-state 2H NMR relaxation. The relaxation data collected for a range of temperatures can be fit using analytical models for the internal dynamics of these compounds to yield physical parameters such as activation energies and diffusion constants that quantify the different modes of motion. Here, we performed quadrupolar-echo and relaxation experiments on powdered samples of deuterated amantadine, rimantadine, and HMB for temperatures between −150⁰C and 60⁰C. HMB displayed two rotational modes about its internal symmetry axes with vastly different timescales. Quadrupolar-echo spectra showed that rimantadine exhibits methyl rotation about its 3-fold axis with no rotation about the C-C axis linked to the cage, while amantadine undergoes slow rotation about the cage axis. The order parameters calculated from the residual quadrupolar couplings for all three compounds were large (>0.8), indicating restricted off-axial dynamics. Spin-lattice (T1Z) and quadrupolar-order relaxation times (T1Q) were calculated for different orientations within the polycrystalline samples. The temperature and angular dependences of these relaxation times were fit using three models: anisotropic rotational diffusion [1,2], axial diffusion, and discrete jumps, among which the anisotropic rotational diffusion model displayed universal applicability. Application of NMR relaxometry to these drugs within the membrane channel will further enable us to understand their activity and the effect of the lipid environment on their structural dynamics.

Exploring Molecular Dynamics of Adsorbed CO2 Species in Amine-Modified Porous Silica by Solid-State NMR Relaxation.

Previous studies on CO2 adsorbents have mainly addressed the identification and quantification of adsorbed CO2 species in amine-modified porous materials. Investigation of molecular motion of CO2 species in confinement has not been explored in depth yet. This work entails a comprehensive study of molecular dynamics of the different CO2 species chemi- and physisorbed at amine-modified silica materials through the determination of the rotating frame spin–lattice relaxation times (T1ρ) by solid-state NMR. Rotational correlation times (τC) were also estimated using spin relaxation models based on the Bloch, Wangsness, and Redfield and the Bloembergen–Purcell–Pound theories. As expected, the τC values for the two physisorbed CO2 species are considerably shorter (32 and 20 μs) than for the three identified chemisorbed CO2 species (162, 62, and 123 μs). The differences in molecular dynamics between the different chemisorbed species correlate well with the structures previously proposed. In the case of the physisorbed CO2 species, the τC values of the CO2 species displaying faster molecular dynamics falls in the range of viscous liquids, whereas the species presenting slower dynamics exhibit T1ρ and τC values compatible with a CO2 layer of weakly interacting molecules with the silica surface. The values for chemical shift anisotropy (CSA) and 1H–13C heteronuclear dipolar couplings have also been estimated from T1ρ measurements, for each adsorbed CO2 species. The CSA tensor parameters obtained from fitting the relaxation data agree with the experimentally measured CSA values, thus showing that the theories are well suited to study CO2 dynamics in silica surfaces.

Molecular Dynamics and Surface Interactions of Nickelocene Adsorbed on Silica: A Paramagnetic Solid-State NMR Study.

When grinding nickelocene with silica in the absence of a solvent at room temperature, it adsorbs on the surface within the pores. This has also been demonstrated visually by adsorbing green nickelocene in the pores of a large colorless silica gel specimen. While this dry adsorption and translational mobility of nickelocene within the pores is proven visually, the site-to-site mobility of the nickelocene molecules and their orientation toward the surface are not yet understood. In this contribution, mesoporous silica is used as the support material for a systematic solid-state NMR study of these issues. Paramagnetic 1H VT solid-state NMR and T1 relaxation times have been powerful tools for studying the dynamics of nickelocene on the silica surface. Herewith, the mobility of the surface-adsorbed nickelocene molecules in the pores could be quantified on the molecular scale. According to the obtained data, the nickelocene molecules move like a liquid on the surface. Isotropically moving molecules exchange places rapidly with surface-attached molecular states of nickelocene in a sample with submonolayer surface coverage. This finding is corroborated by a macroscopic visualization experiment. The states of the surface-attached horizontally oriented nickelocene molecules that are prevalent at temperatures below 200 K have been quantified. The temperature dependencies of the rate k in coordinates of ln(k) versus 1/T and ln(k/T) versus 1/T form ideal straight lines that allow the determination of the kinetic parameters Eact = 5.5 kcal/mol, A = 1.1 × 1010, ΔH‡ = 5.0 kcal/mol, and ΔS‡ = -15 eu. Investigating a sample with equal amounts of nickelocene and ferrocene in a submonolayer amount of 80% overall surface coverage shows that the different metallocenes mix on the molecular level on the silica surface.

Model-Free or Not?

Relaxation in nuclear magnetic resonance is a powerful method for obtaining spatially resolved, timescale-specific dynamics information about molecular systems. However, dynamics in biomolecular systems are generally too complex to be fully characterized based on NMR data alone. This is a familiar problem, addressed by the Lipari-Szabo model-free analysis, a method that captures the full information content of NMR relaxation data in case all internal motion of a molecule in solution is sufficiently fast. We investigate model-free analysis, as well as several other approaches, and find that model-free, spectral density mapping, LeMaster’s approach, and our detector analysis form a class of analysis methods, for which behavior of the fitted parameters has a well-defined relationship to the distribution of correlation times of motion, independent of the specific form of that distribution. In a sense, they are all “model-free.” Of these methods, only detectors are generally applicable to solid-state NMR relaxation data. We further discuss how detectors may be used for comparison of experimental data to data extracted from molecular dynamics simulation, and how simulation may be used to extract details of the dynamics that are not accessible via NMR, where detector analysis can be used to connect those details to experiments. We expect that combined methodology can eventually provide enough insight into complex dynamics to provide highly accurate models of motion, thus lending deeper insight into the nature of biomolecular dynamics.

Membrane Deformation Modulated by Hydration and Cholesterol Unveiled by Solid-State 2H NMR Spectroscopy

Phospholipid membranes are biological liquid crystals in which intermolecular interactions at mesoscopic length scales play key roles in the emergence of membrane physical properties like structure and rigidity. Such interactions modulated by membrane hydration [1] and cholesterol [2] have been investigated using solid-state 2H NMR spectroscopy. The average structure is manifested by the lineshapes through principal values of static or residual coupling tensors due to quadrupolar interactions. The residual quadrupolar couplings (RQCs) yield segmental order parameters for the individual acyl segments (i), providing average membrane properties such as bilayer thickness, area/lipid, and spontaneous curvature [3]. We show that membrane dehydration and increased cholesterol content result in greater RQCs, indicative of membrane thickening. Elastic membrane deformations are exhibited as collective order-director fluctuations (ODF) contributing to the nuclear magnetic relaxation. At mesoscopic length scales the thermal fluctuations connect to membrane mechanical properties via the fluctuation-dissipation theorem. Model-free interpretation of the functional dependence of spin-lattice relaxation rates, R1Z, on segmental order parameters (square-law) reveals emergent material properties in the liquid-crystalline state. The R1Z relaxation dispersion and temperature dependence of square-law plots indicate a nematic-like membrane hydrocarbon core. Solid-state 2H NMR relaxation studies demonstrate that both dehydration and increased cholesterol content in the membrane lead to decreased slopes of square-law plots, indicating an increase in membrane bending rigidity, consistent with neutron spin-echo (NSE) measurements. Analogous 2H NMR studies with various membrane lipid compositions and peptide-reconstituted membranes have addressed lipid-mediated cell signaling and lipid-protein interactions. Molecular dynamics simulations provide further insights on the correspondence of the solid-state NMR and NSE results. [1] K.J. Mallikarjunaiah et al. (2019) Phys. Chem. Chem. Phys. 21, 18422. [2] S. Chakraborty et al. (2020) Proc. Natl. Acad. Sci. 117, 21896. [3] Mallikarjunaiah et al. (2011) Biophys. J. 100, 98.

Correlative analysis between solid-state NMR and morphology for blends of poly(lactic acid) and poly(butylene adipate-co-butylene terephthalate)

Morphological changes in polymer blending process were investigated using integrated analyses by solid-state NMR and magnetic relaxation. The study examined previous reported mechanical properties of polymer blends incorporating poly(lactic acid) (PLA) and poly(butylene adipate-co-butylene terephthalate) (PBAT) over a range of compositions, along with a crosslinking reagent. The X-ray diffraction (XRD) and the differential scanning calorimeter (DSC) results showed that the crystallinity of PLA decreased with increasing the PBAT content. According to the integrated analysis data and imaging by micro-focus X-ray computed tomography (CT), polymer tensile properties were dominated by interfacial affinity between the molecular mobilities of PLA and PBAT; depending on the blending ratio, the polymer morphology changed from a discontinuous “sea-island” form to a bicontinuous morphology. Addition of a crosslinking reagent was observed via X-ray CT to homogenize the PLA and PBAT blend at the micron length scale, even though both polymers were still heterogeneous at the nanoscale as elucidated by NMR analysis. As well as the morphological change in micro scale, the molecular mobility changes of the total polymer blend system, which could be evaluated by the integrated solid-state NMR analyses, brought about greater elongation at the break point in dynamic tensile testing.

Application of solid-state 13C relaxation time to prediction of the recrystallization inhibition strength of polymers on amorphous felodipine at low polymer loading.

The potential for inhibiting recrystallization with Eudragit® L (EUD-L), hypromellose acetate succinate (HPMC-AS), and polyvinylpyrrolidone-co-vinylacetate (PVP-VA) on amorphous felodipine (FLD) at low polymer loading was investigated in this study. The physical stabilities of the FLD/polymer amorphous solid dispersions (ASDs) were investigated through storage at 40°C. The HPMC-AS and PVP-VA strongly inhibited FLD recrystallization, although EUD-L did not effectively inhibit the FLD recrystallization. The rotating frame 1H spin-lattice relaxation time (1H-T1ρ) measurement clarified that EUD-L was not well mixed with FLD in the ASD, which resulted in weak inhibition of recrystallization by EUD-L. In contrast, the HPMC-AS and PVP-VA were well mixed with the FLD in the ASDs. Solid-state 13C spin-lattice relaxation time (13C-T1) measurements at 40°C showed that the molecular mobility of the FLD was strongly suppressed when mixed with polymer. The reduction in the molecular mobility of FLD was in the following order, starting with the least impact: FLD/EUD-L ASD, FLD/HPMC-AS ASD, and FLD/PVP-VA ASD. FLD mobility at the storage temperature, evaluated by 13C-T1, showed a good correlation with the physical stability of the amorphous FLD. The direct investigation of the molecular mobility of amorphous drugs at the storage temperature by solid-state NMR relaxation time measurement can be a useful tool in selecting the most effective crystallization inhibitor at low polymer loading.

Fast Microsecond Dynamics of the Protein-Water Network in the Active Site of Human Carbonic Anhydrase II Studied by Solid-State NMR Spectroscopy.

Protein-water interactions have widespread effects on protein structure and dynamics. As such, the function of many biomacromolecules can be directly related to the presence and exchange of water molecules. While the presence of structural water sites can be easily detected by X-ray crystallography, the dynamics within functional water-protein network architectures is largely elusive. Here we use solid-state NMR relaxation dispersion measurements with a focus on those active-site residues in the enzyme human carbonic anhydrase II (hCAII) that constitute the evolutionarily conserved water pocket, key for CAs' enzymatic catalysis. Together with chemical shifts, peak broadening, and results of molecular dynamics (MD) and DFT shift calculations, the relaxation dispersion data suggest the presence of a widespread fast μs-time-scale dynamics in the pocket throughout the protein-water network. This process is abrogated in the presence of an inhibitor which partially disrupts the network. The time scale of the protein-water pocket motion coincides both with the estimated residence time of Zn-bound water/OH- in the pocket showing the longest lifetimes in earlier magnetic relaxation dispersion experiments as well as with the rate-limiting step of catalytic turnover. As such, the reorganization of the water pocket:enzyme architecture might constitute an element of importance for enzymatic activity of this and possibly other proteins.

Integrated analysis of modified Japanese cypress using solid-state NMR spectra and nuclear magnetic relaxation times

Acetylation and resin impregnation of Japanese cypress and subsequent heating of these modified cypresses were examined using an integrated analysis of solid-state NMR spectra and relaxation times. The 1H magic angle spinning NMR showed altered moisture balance after chemical and thermal modifications because of changed hydrophobicity. The 13C cross-polarization/magic angle spinning (CP-MAS) NMR spectra showed that acetylation predominately occurred for carbohydrates while phenol formaldehyde (PF) and melamine formaldehyde (MF) resins permeated all biomass constituents in cypress samples. Spin–lattice relaxation times in the laboratory frame, T1H and T1C, increased with chemical modifications although T1C decreased with the curing of both resins. In contrast, 1H spin–lattice relaxation in the rotation frame, T1ρH, increased with the curing as well as acetylation. The tendencies of relaxation times with curing suggested that faster molecular motions were suppressed in the MHz frequency range, and slower molecular motions were enhanced in the kHz frequency range, which generally matched with the signal changes in the 13C pulse saturation transfer/magic angle spinning NMR spectra. Scanning electron microscope observation showed different adhesion distribution between PF and MF resins, affecting the cellulose signals of 13C CP-MAS NMR and T1H change due to the curing.

Variable temperature solid-state NMR spectral and relaxation analyses of the impregnation of polyethylene glycol (PEG) into coniferous wood.

To investigate the behaviours of polyethylene glycol (PEG) and its interaction with biomass constituents in coniferous wood (Japanese cypress), variable temperature solid-state NMR spectra and relaxation times were measured from 20–80 °C. Signal intensities in the 1H and 13C PST-MAS NMR spectra changed depending on both the measurement temperature and the melting point of the impregnated PEG. In the 13C CP-MAS NMR spectra with increasing temperature, although the signal intensities of biomass constituents slightly decreased, signal intensities of PEG molecules in the cypress maximized at 80 °C. PEG impregnation into cypress decreased the T1H values at 80 °C for short to medium chain PEG in the liquid phase while it decreased T1H values at ambient temperature for long chain PEG in the solid phase because the interactions of PEG molecules and the biomass constituents of coniferous wood were different for different chain lengths of the PEG. These variable temperature measurements of both solid-state NMR spectra and relaxation time indicated that impregnation of longer chain PEG molecules produced higher hydrophobicity because of the increased steric hinderance of PEG attached to carbohydrates. The variable temperature measurements also showed that long chain PEG molecules were restricted to the lumen while short to medium chain length PEG molecules infiltrated into the intercellular region of the cell wall in addition to the lumen. These results obtained from the variable temperature NMR measurements were also supported by ATR-IR spectroscopy analyses.

Dynamics of Alanine Methyl Groups in Alanine Oligopeptides and Spider Dragline Silks with Different Packing Structures As Studied by 13C Solid-State NMR Relaxation

The dynamics of alanine methyl groups in alanine oligopeptides and polyalanine regions in Nephila clavata dragline and recombinant silks changed remarkably depending on the different packing arrangements. In particular, a notable difference in the 13C spin–lattice relaxation time T1 of Ala Cβ peaks was observed in the solid-state NMR between (Ala)6 and (Ala)7, which have rectangular and staggered packing arrangements, respectively. Moreover, the remarkably longer T1 value of the lowest field peak in Ala Cβ carbons clearly indicated the presence of staggered packing structure. Then, the relaxation behavior of polyalanine regions in spider dragline silks with mixed packing arrangements were clarified in both dry and hydrated states. The partial appearance of the staggered packing structure in (Ala)6 with rectangular packing structure was detected from the changes in line shapes of Ala 13Cβ peaks for the three kinds of 13C single-labeled (Ala)6 samples together with the change in their relaxation behavior.

Instrumental analyses of nanostructures and interactions with bound water of superheated steam treated plant materials

Using multi-scale instrumental analyses, nanostructural changes due to superheated steam treatments were compared between Japanese cedar (Cryptomeria japonica) and bamboo (Phyllostachys pubescens Mazel). The lower amounts of aromatic carboxylic acids contained in lignin and hemicellulose/lignin in Japanese cedar suppressed not only the formation of pyrolysis products from hemicellulose but also fragmentation of cell walls. Variable temperature solid-state NMR spectra and relaxation time analyses were carried out on the nanostructures of the plant materials in order to examine molecular motions and interaction with bound water for the biomass constituents of the plant materials. The untreated and steam treated bamboos strongly interacted with bound water to change the 1H spin-lattice relaxation time (T1H) values depending on the content of bound water. Because the interaction between the biomass constituents and bound water in Japanese cedar was weaker than that in bamboo, the T1H values of Japanese cedar were reduced less than those of bamboo in the humid conditions. The difference in the interaction with bound water between bamboo and Japanese cedar also affected the amount of the pyrolysis products and the decomposition rate of hemicellulose in the superheated steam treated materials. Furthermore, the pyrolysis products caused little change in the molecular mobility of Japanese cedar although they restrained that of bamboo.

Framework vs. side-chain amphidynamic behaviour in oligo-(ethylene oxide) functionalised covalent-organic frameworks.

We present a family of covalent organic frameworks that have been functionalized with oligo-(ethylene oxide) chains of varying lengths. Because of the open structure of the COFs, the side chains do not interfere with their crystallization obtaining materials with predictable crystal structure. The difference in length of the side-chains allowed for the determination of amphidynamic behaviour with the use of 13C solid-state NMR relaxation methods. Computational calculations further contribute to understanding the atomistic dynamic behaviour of the different atoms. This study demonstrates the ability to design complex behaviour in organic crystals.

Solvent-Driven Dynamical Crossover in the Phenylalanine Side-Chain from the Hydrophobic Core of Amyloid Fibrils Detected by 2H NMR Relaxation.

Aromatic residues are important markers of dynamical changes in proteins' hydrophobic cores. In this work we investigated the dynamics of the F19 side-chain in the core of amyloid fibrils across a wide temperature range of 300 to 140 K. We utilized solid-state 2H NMR relaxation to demonstrate the presence of a solvent-driven dynamical crossover between different motional regimes, often also referred to as the dynamical transition. In particular, the dynamics are dominated by small-angle fluctuations at low temperatures and by π-flips of the aromatic ring at high temperatures. The crossover temperature is more than 43 degrees lower for the hydrated state of the fibrils compared to the dry state, indicating that interactions with water facilitate π-flips. Further, crossover temperatures are shown to be very sensitive to polymorphic states of the fibrils, such as the 2-fold and 3-fold symmetric morphologies of the wild-type protein as well as D23N mutant protofibrils. We speculate that these differences can be attributed, at least partially, to enhanced interactions with water in the 3-fold polymorph, which has been shown to have a water-accessible cavity. Combined with previous studies of methyl group dynamics, the results highlight the presence of multiple dynamics modes in the core of the fibrils, which was originally believed to be quite rigid.

31P Solid-State NMR Relaxation in the Zirconium Phosphate Network in the Presence of Paramagnetic Centers: A Detailed Relaxation Study in Static and Rotating Samples of Layered Zirconium Phosphate Materials

The careful study of MAS effects on the spin–lattice and spin–spin phosphorus NMR relaxation in two layered zirconium phosphate materials, α-ZrP and m-PEG-PO3/Zr(IV)/DOX/ZrP, has clearly shown that the fast spin-diffusion and limited spin-diffusion mechanisms are completely negligible in spite of the presence of paramagnetic centers detected in these materials by EPR. The 31P T1 relaxation is always nonexponential in static and spinning samples as well. The 31P T1 relaxation in α-ZrP follows a stretched exponential law to show the presence of a 31P T1 distribution. The 31P T1 time remarkably depends on spinning rates only in a 7 mm NMR probe head due to the frictional heating effects in 7 mm rotors but not due to the spin-diffusion mechanism. In accord, the 31P T1 and T2 times are independent of MAS rates in the experiments performed with 2.5 mm rotors. All the 31P T1 and T2 relaxation data support well the interpretation of the 31P T1 times in the zirconium phosphate network by dipolar proton–phosphorus interactions and justify the application of the 31P T1 and 31P T1/T2 approaches to probing molecular mobility in zirconium phosphate materials.

Fast Motions of Key Methyl Groups in Amyloid-β Fibrils

Amyloid-β (Aβ) peptide is the major component of plaques found in Alzheimer’s disease patients. Using solid-state 2H NMR relaxation performed on selectively deuterated methyl groups, we probed the dynamics in the threefold symmetric and twofold symmetric polymorphs of native Aβ as well as the protofibrils of the D23N mutant. Specifically, we investigated the methyl groups of two leucine residues that belong to the hydrophobic core (L17 and L34) as well as M35 residues belonging to the hydrophobic interface between the cross-β subunits, which has been previously found to be water-accessible. Relaxation measurements performed over 310–140 K and two magnetic field strengths provide insights into conformational variability within and between polymorphs. Core packing variations within a single polymorph are similar to what is observed for globular proteins for the core residues, whereas M35 exhibits a larger degree of variability. M35 site is also shown to undergo a solvent-dependent dynamical transition in which slower amplitude motions of methyl axes are activated at high temperature. The motions, modeled as a diffusion of methyl axis, have activation energy by a factor of 2.7 larger in the twofold compared with the threefold polymorph, whereas D23N protofibrils display a value similar to the threefold polymorph. This suggests enhanced flexibility of the hydrophobic interface in the threefold polymorph. This difference is only observed in the hydrated state and is absent in the dry fibrils, highlighting the role of solvent at the cavity. In contrast, the dynamic behavior of the core is hydration-independent.

The Li-Ion and Na-Ion Diffusion Mechanism in Halogen Substituted Solid Sulfide Electrolytes Studied by Solid State NMR and DFT Based Molecular Dynamics Simulations

Both Li-ion and Na-ion all solid state batteries are under development, where the absence of an liquid electrolyte potentially leads to improved safety and higher energy densities. Both the bulk ionic conductivity, as well as the conductivity over the electrolyte-electrolyte and electrolyte-electrode interfaces are prerequisites for efficient charge transport in solid state batteries. In many solid electrolytes the bulk mobility can be improved by introducing dopants that control the site occupancies by charge compensation. On the other hand the impact of solid-solid interfaces is anticipated to be one of the major bottlenecks towards high performance solid state batteries, making it of large importance to characterize the transport in detail. The present study provides detailed insight in the Na-ion and Li-ion conductivity in Na3PS4 1 and Li6PS5Cl2 sulfide solid electrolytes. The relative contribution of the bulk conductivity versus the conductivity over the solid-solid electrolyte and solid-solid electrolyte-electrode interfaces is revealed by comparing solid state NMR relaxation experiments with impedance spectroscopy. In addition X-ray and Neutron diffraction is performed to characterize the structures in detail. The structure and self diffusion measured by NMR is compared to DFT based Molecular Dynamics (MD) simulations that reveal the diffusion mechanism and the impact of halogen substitution in both cubic/tetragonal Na3PS4 (Na3-yPS4-yXy, X=Cl,Br,…) and argyrodite Li7PS6 (Li6PS5X, X=Cl,Br,…) structures. Solid state NMR relaxation experiments, shown in Figure 1c for Li6PS5Br, have the ability to directly probe the atomic scale Li-ion mobility in solid electrolytes and electrode materials3-6offering a non-destructive method to probe the self-diffusion coefficients. Conversion to solid state conductivities allows complementary information to impedance spectroscopy, for instance giving insight in the role of grain boundaries on the overall conductivity, as illustrated in Figure 1d. DFT MD-simulations, shown for Li6PS5Br in Figure 1a and 1b, allow to develop understanding of the diffusion mechanism of Li-ions and Na-ions in solid electrolytes and how these structures may be optimized to yield higher bulk conductivities. By systematically varying the halogen element to introduce Na-ion vacancies in both cubic/tetragonal Na3PS4 (Na3-yPS4-yXy, X=Cl,Br,…) and in argyrodite Li7PS6 (Li6PS5X, X=Cl,Br,…) structures, the simulations reveal the impact of vacancies and the host structure on the conductivity. This gives insight why and what halogen dopant results in optimal structural conditions to improve the Na-ion and Li-ion conductivity. By combining solid state NMR, Impedance, XRD and ND with DFT MD simulations, this study provides detailed insight in the Na-ion and Li-ion diffusion mechanism in in both cubic/tetragonal Na3PS4 (Na3-yPS4-yXy, X=Cl,Br,…) and argyrodite Li7PS6 (Li6PS5X, X=Cl,Br,…) solid electrolytes and potential routes to improve its performance in all solid state batteries. (1) Hayashi, A.; Noi, K.; Sakuda, A.; Tatsumisago, M. Nature Communications 2012, 3. (2) Deiseroth, H.-J.; Kong, S.-T.; Eckert, H.; Vannahme, J.; Reiner, C.; Zaiss, T.; Schlosser, M. Angewandte Chemie-International Edition 2008, 47, 755. (3) Wagemaker, M.; van Eck, E. R. H.; Kentgens, A. P. M.; Mulder, F. M. Journal of Physical Chemistry B 2009, 113, 224. (4) Wagemaker, M.; Kentgens, A. P. M.; Mulder, F. M. Nature 2002, 418, 397. (5) Schmidt, W.; Bottke, P.; Sternad, M.; Gollob, P.; Hennige, V.; Wilkening, M. Chemistry of Materials 2015, 27, 1740. (6) Epp, V.; Gun, O.; Deiseroth, H.-J.; Wilkening, M. Journal of Physical Chemistry Letters 2014, 4, 2118. (7) Tanibata, N.; Noi, K.; Hayashi, A.; Kitamura, N.; Idemoto, Y.; Tatsumisago, M. Chemelectrochem 2014, 1, 1130. Figure 1. (a) The Li-density and (b) Li-ion jumps for Li6PS5Br at 600 K from DFT molecular dynamics simulations. (c) 7Li NMR spin-lattice relaxation rates 1/T1 (at 155.506MHz) of Li6PS5Br which allows to deduce the hopping rate and activation energy for Li-ion self-diffusion. (d) Temperature-dependence of Li jump rates of Li6PS5Br obtained from MD calculations and deduced from 7Li static SLR NMR measurements. The dash line in the figure shows an Arrhenius activation energy of 0.18 eV for bulk self-diffusion and s indicates the macroscopic conductivity measured with impedance spectroscopy. The lower value of s implies that diffusion over the grain boundary between different Li6PS5Br grains is limiting the conductivity of Li6PS5Br electrodes. Figure 1

Elastic Deformation and Collective Dynamics in Lipid Membranes: A Solid-State 2H NMR Relaxation Study

Biomembrane functioning is significantly influenced by the composition and structure of the liquid-crystalline lipid bilayer [1]. Solid-state 2H NMR spectroscopy provides information about atomistic interactions among the membrane constituents by simultaneously probing structure and dynamics [2]. Here we examine the effect of water, osmolytes, cholesterol, and detergents on the liquid-crystalline properties of lipid membranes using NMR relaxation methods. We performed 2H NMR longitudinal (R1Z) and transverse quadrupolar-echo decay (R2QE) experiments on DMPC-d54 bilayers to study membrane lipid dynamics over the time scale ranging from nanoseconds to milliseconds. Plots of R1Z rates or transverse relaxation rates versus squared segmental order parameters (SCD2) show the emergence of collective lipid dynamics [3]. Such a functional behavior characterizes 3-D order-director fluctuations, due to the onset of membrane elasticity [3]. Yet at high hydration, a further R2QE enhancement and confinement of the functional square-law to the segments deeper in the bilayer is seen. Additional contributions from slower dynamics involving water-mediated membrane deformation are evident over mesoscopic length scales on the order of bilayer thickness. Such structural deformations are also evident from bilayer structural parameters calculated using a statistical mean-torque model [4]. The slow dynamics at high hydration or correspondingly low cholesterol or osmolyte concentration are due to modulation of elastic properties of the lipid bilayer. Analysis of the frequency dispersion of the transverse relaxation as a function of such external parameters reveals viscoelastic properties of the liquid-crystalline membranes. Such studies give insights into lipid rafts and membrane composition relevant for biomembrane function. [1] A. Leftin et al. (2014) Biophys. J. 107, 2274[2] K.J. Mallikarjuniah et al. (2011) Biophys. J.100, 98. [3] A. Leftin et al. (2014) eMagRes 4, 199. [4] J.J. Kinnun et al. (2015) BBA 1848, 246.