Pulsed Field Gradient NMR Diffusion Research Articles

Nonstoichiometric Protic Ionic Liquids: The Role of Excess Acid in Charge Transport Mechanisms.

A study of charge transport mechanisms in an electric field was conducted on nonstoichiometric protic ionic liquids (PIL) based on triethylamine (TEA), in combination with an excess of either trifluoroacetic acid (TFA) or trifluoromethanesulfonic acid (TfO). The addition of excess precursor acid adds proton-donor sites to the system to support potential structural proton transport, which could, for example, enable the use in fuel cells. Transport measurements by pulsed field gradient (PFG) NMR diffusion and, in particular, electrophoretic NMR (eNMR) are supported by NMR chemical shifts and Raman spectroscopy, where the latter techniques elucidate the local solvation structures. Migration of the acidic proton of the excess acid in the electric field occurs toward the cathode with a velocity larger than that of the anions. This intriguing feature of a rapid drift of a neutral molecule is explained by the interplay of strong correlations between anion and cation as well as between anion and acid. The neutral acid is subject to vehicular transport with the anion, while the anion is partitioning between anion-acid and anion-cation clusters, resulting in a lower average drift velocity. The negative drift direction of the neutral acid and its proton is superimposed to and thus counteracts the vehicular transport of protons with the cation. The study sheds light on the role of excess acid in PIL and reveals the versatile interactions between anion, cation, and excess acid within a PIL determining its charge transport properties.

Assessment of models for calculating the hydrodynamic radius of intrinsically disordered proteins

Diffusion measurements by pulsed-field gradient NMR and fluorescence correlation spectroscopy can be used to probe the hydrodynamic radius of proteins, which contains information about the overall dimension of a protein in solution. The comparison of this value with structural models of intrinsically disordered proteins is nonetheless impaired by the uncertainty of the accuracy of the methods for computing the hydrodynamic radius from atomic coordinates. To tackle this issue, we here build conformational ensembles of 11 intrinsically disordered proteins that we ensure are in agreement with measurements of compaction by small-angle x-ray scattering. We then use these ensembles to identify the forward model that more closely fits the radii derived from pulsed-field gradient NMR diffusion experiments. Of the models we examined, we find that the Kirkwood-Riseman equation provides the best description of the hydrodynamic radius probed by pulsed-field gradient NMR experiments. While some minor discrepancies remain, our results enable better use of measurements of the hydrodynamic radius in integrative modeling and for force field benchmarking and parameterization.

Investigation of domain structures in monomethoxy poly(ethylene glycol)‐b‐poly(caprolactone) grafted poly(acrylic acid) by NMR diffusion studies

AbstractAssociating polymers developed by grafting a block copolymer of monomethoxy poly(ethylene glycol)‐b‐poly(caprolactone) (MPEG‐b‐PCL) onto poly(acrylic acid) undergo an irreversible sol–gel transition on heating. The influence of various physicochemical parameters on the thermoresponsive behaviour was examined by rheology and NMR studies. Pulsed field gradient NMR diffusion studies were performed to probe the mechanism of thermally induced gelation. Analysis of the diffusion data reveals the presence of loosely and strongly associated structures which respond differently to variation in temperature. It is observed that the polymer solution, which is visibly homogeneous, is heterogeneous on a mesoscopic scale with a distribution of domains. Detailed investigation of the thermally induced sol–gel transition shows that the mechanism of gelation involves irreversible alterations in the domain structure and size. © 2022 Society of Industrial Chemistry.

NMR investigation of the thermogelling properties, anomalous diffusion, and structural changes in a Pluronic F127 triblock copolymer in the presence of gold nanoparticles

We studied the thermogelation of a triblock copolymer Pluronic F127 (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)) in an aqueous solvent in the presence of gold nanoparticles, using pulsed field gradient diffusion, NMR temperature experiments, relaxation measurements, and 2D heteronuclear NMR experiments. Pulsed field gradient diffusion NMR is a powerful technique to study the transition between diffusive regimes in a polymer mesh which are modulated by phase transitions in the polymeric network. In the isotropic phase, the triblock copolymer diffusion is a classical Fickian process. As the onset of gelation occurs, diffusion in the system becomes anomalous and the mean square displacement in the direction of the applied magnetic field gradient shows a power law dependence. Our experiments show that the introduction of gold nanoparticles leads to a disruption of gelation and the shifting of the formation of the ordered phase of the triblock copolymer to a higher temperature.

Potentials and challenges of high-field PFG NMR diffusion studies with sorbates in nanoporous media

High magnetic fields (up to 17.6 T) in combination with large magnetic field gradients (up to 25 T/m) were successfully utilized in pulsed field gradient (PFG) NMR studies of gas and liquid diffusion in nanoporous materials. In this mini-review, we present selected examples of such studies demonstrating the ability of high field PFG NMR to gain unique insights and differentiate between various types of diffusion. These examples include identifying and explaining an anomalous relationship between molecular size and self-diffusivity of gases in a zeolitic imidazolate framework (ZIF), as well as revealing and explaining an influence of mixing different linkers in a ZIF on gas self-diffusion. Different types of normal and restricted self-diffusion were quantified in hybrid membranes formed by dispersing ZIF crystals in polymers. High field PFG NMR studies of such membranes allowed observing and explaining an influence of the ZIF crystal confinement in a polymer on intra-ZIF self-diffusion of gases. This technique also allowed measuring and understanding anomalous single-file diffusion (SFD) of mixed sorbates. Furthermore, the presented examples demonstrate a high potential of combining high field PFG NMR with single-crystal infrared microscopy (IRM) for obtaining greater physical insights into the studied diffusion processes.

Protein structural changes characterized by high-pressure, pulsed field gradient diffusion NMR spectroscopy

Pulsed-field gradient NMR spectroscopy is widely used to measure the translational diffusion and hydrodynamic radius (Rh) of biomolecules in solution. For unfolded proteins, the Rh provides a sensitive reporter on the ensemble-averaged conformation and the extent of polypeptide chain expansion as a function of added denaturant. Hydrostatic pressure is a convenient and reversible alternative to chemical denaturants for the study of protein folding, and enables NMR measurements to be performed on a single sample. While the impact of pressure on the viscosity of water is well known, and our water diffusivity measurements agree closely with theoretical expectations, we find that elevated pressures increase the Rh of dioxane and other small molecules by amounts that correlate with their hydrophobicity, with parallel increases in rotational friction indicated by 13C longitudinal relaxation times. These data point to a tighter coupling with water for hydrophobic surfaces at elevated pressures. Translational diffusion measurement of the unfolded state of a pressure-sensitized ubiquitin mutant (VA2-ubiquitin) as a function of hydrostatic pressure or urea concentration shows that Rh values of both the folded and the unfolded states remain nearly invariant. At ca 23 Å, the Rh of the fully pressure-denatured state is essentially indistinguishable from the urea-denatured state, and close to the value expected for an idealized random coil of 76 residues. The intrinsically disordered protein (IDP) α-synuclein shows slight compaction at pressures above 2 kbar. Diffusion of unfolded ubiquitin and α-synuclein is significantly impacted by sample concentration, indicating that quantitative measurements need to be carried out under dilute conditions.

NMR Investigation into the Influence of Surface Interactions on Liquid Diffusion in a Mesoporous Catalyst Support

Pulsed field gradient NMR diffusion measurements provide a non-invasive measure of the mass transport (self-diffusion) characteristics of liquids confined to porous catalyst materials. Here we explore the ability of this technique to probe the diffusive behaviour of a series of short-chain primary alcohols within a mesoporous catalyst support material; through the comparison of our results with highly surface-sensitive NMR relaxation data, we show that the evaluation of bulk-pore diffusion dynamics may provide a simple and indirect method to access and explore surface interaction phenomena occurring at the catalyst-liquid interface.

Anomalous Relationship between Molecular Size and Diffusivity of Ethane and Ethylene inside Crystals of Zeolitic Imidazolate Framework-11

Multinuclear pulsed field gradient (PFG) NMR was used to study the self-diffusion of ethane and ethylene inside loosely packed beds of zeolitic imidazolate framework-11 (ZIF-11) crystals. Diffusion measurements were performed at different temperatures under conditions where the length scales of displacements were smaller than or comparable with the mean size of the ZIF-11 crystals. For the crystal beds loaded with a single sorbate, these studies showed a larger intracrystalline diffusivity for ethane than that for ethylene under the same or comparable experimental conditions, an unexpected result due to the larger size of ethane compared to that of ethylene. PFG NMR diffusion studies of ZIF-11 beds loaded with ethane/ethylene mixtures revealed that substituting a fraction of ethane molecules by ethylene molecules decreases the intracrystalline diffusivity of ethane. These results in combination with an observation of a higher-for-ethylene-than-for-ethane activation energy of intracrystalline self-diffusio...

Structural and dynamical aspects of PEG/LiClO4 in solvent mixtures via NMR spectroscopy.

Motivated by the potential usefulness of polyethylene glycol (PEG)/Li+ salt mixtures in several industrial applications, we investigated the structure and dynamics of PEG/LiClO4 mixtures in D2 O and its mixtures with CD3 CN and DMSO-d6 , in a series of PEG-based polymers with a wide variation in their molecular weights. 1 H NMR chemical shifts, T1 /T2 relaxation rates, pulsed-field gradient NMR diffusion experiments, and 2D HOESY NMR studies have been performed to understand the structural and dynamical aspects of these mixtures. Increasing the temperature of the medium results in a significant perturbation in the H-bonded structure of PEG in its PEG/LiClO4 /D2 O mixtures as observed from the increase in chemical shifts. On the other hand, the addition of molecular cosolvents has a negligible effect. The hydrodynamic structure of PEG shows a pronounced variation at low temperature with increasing molecular weight, which, however, disappears at higher temperatures. Increasing the temperature leads to a decrease in the hydrodynamic structure of PEG, which can be explained on the basis of solvation-desolvation phenomena. The 2D HOESY NMR spectra reveal a new finding of Li+ -water binding in the PEG/LiClO4 /D2 O mixtures with the addition of molecular solvents, suggesting that the Li+ cation diffuses freely in the D2 O mixtures of polymers as compared with the polymer mixtures with DMSO or CD3 CN.

Tracing compartment exchange by NMR diffusometry: Water in lithium-exchanged low-silica X zeolites

The two-region model for analyzing signal attenuation in pulsed field gradient (PFG) NMR diffusion studies with molecules in compartmented media implies that, on their trajectory, molecules get from one region (one type of compartment) into the other one with a constant (i.e. a time-invariant) probability. This pattern has proved to serve as a good approach for considering guest diffusion in beds of nanoporous host materials, with the two regions (“compartments”) identified as the intra- and intercrystalline pore spaces. It is obvious, however, that the requirements of the application of the two-region model are not strictly fulfilled given the correlation between the covered diffusion path lengths in the intracrystalline pore space and the probability of molecular “escape” from the individual crystallites. On considering water diffusion in lithium-exchanged low-silica X zeolite, we are now assuming a different position since this type of material is known to offer “traps” in the trajectories of the water molecules. Now, on attributing the water molecules in the traps and outside of the traps to these two types of regions, we perfectly comply with the requirements of the two-region model. We do, moreover, benefit from the option of high-resolution measurements owing to the combination of magic angle spinning (MAS) with PFG NMR. Data analysis via the two-region model under inclusion of the influence of nuclear magnetic relaxation yields satisfactory agreement between experimental evidence and theoretical estimates. Limitations in accuracy are shown to result from the fact that mass transfer outside of the traps is too complicated for being adequately reflected by simple Fick’s laws with but one diffusivity.

Inhibitory effect of oxygenated heterocyclic compounds in mesoporous catalytic materials: A pulsed-field gradient NMR diffusion study

Oxygenated heterocyclic compounds are often used as solvents in liquid-phase catalytic reactions, such as hydrogenation and oxidation over porous oxide-based catalysts. It has often been reported that such compounds inhibit catalyst activity relative to the use of hydrocarbons as the solvent media. In this work we use 1H pulsed-field gradient (PFG) NMR diffusion studies to study diffusion properties of binary mixtures 1,4-dioxane/cyclohexane in mesoporous TiO2 over the whole composition range in order to understand the effect of the solid surface on molecular transport and molecular interactions within the pore space. The results reveal that whilst the diffusion of the hydrocarbon is only affected by geometrical restrictions, the diffusion profile of 1,4-dioxane is highly influenced by interactions within the catalyst pore, which is thought to be due to the presence of lone electron pairs on the oxygen atoms of 1,4-dioxane, allowing the molecule to act as a Lewis base when in contact with the solid surface. This agrees with findings on the inhibitory capacity of oxygenated heterocyclic compounds when used either as solvent in catalysis or present as impurities in some chemical feedstocks. The work shows that it is possible to use 1H PFG NMR in order to characterise the effect of surfaces on molecular transport and hence understand catalytic behaviour in liquid-phase catalytic reactions.

Differentiating brown and white adipose tissues by high-resolution diffusion NMR spectroscopy

There are two types of fat tissues, white adipose tissue (WAT) and brown adipose tissue (BAT), which essentially perform opposite functions in whole body energy metabolism. There is a large interest in identifying novel biophysical properties of WAT and BAT by a quantitative and easy-to-run technique. In this work, we used high-resolution pulsed field gradient diffusion NMR spectroscopy to study the apparent diffusion coefficient (ADC) of fat molecules in rat BAT and WAT samples. The ADC of fat in BAT and WAT from rats fed with a chow diet was compared with that of rats fed with a high-fat diet to monitor how the diffusion properties change due to obesity-associated parameters such as lipid droplet size, fatty acid chain length, and saturation. Feeding a high-fat diet resulted in increased saturation, increased chain lengths, and reduced ADC of fat in WAT. The ADC of fat was lower in BAT relative to WAT in rats fed both chow and high-fat diets. Diffusion of fat was restricted in BAT due to the presence of small multilocular lipid droplets. Our findings indicate that in vivo diffusion might be a potential way for better delineation of BAT and WAT in both lean and obese states.

Diffusion in complementary pore spaces

The rate of mass transfer is among the key numbers determining the efficiency of nanoporous materials in their use for matter upgrading by heterogeneous catalysis or mass separation. Transport enhancement by pore space optimization is, correspondingly, among the main strategies of efficiency promotion. Any such activity involves probing and testing of the appropriate routes of material synthesis and post-synthesis modification just as the exploration of the transport characteristics of the generated material. Modelling and molecular simulation is known to serve as a most helpful tool for correlating these two types of activities and their results. The present paper reports about a concerted research activity comprising these three types of activities. Recent progress in producing pore space replicas enabled focusing, in these studies, on “complementary” pore spaces, i.e. on pairs of material, where the pore space of one sample did just coincide with the solid space of the other. We report about the correlations in mass transfer as observable, in this type of material, by pulsed field gradient NMR diffusion studies, with reference to the prediction as resulting from a quite general, theoretical treatment of mass transfer in complementary pore spaces.

Hydrodynamic radii of solubilized high amylose native and modified starches by pulsed field gradient NMR diffusion measurements

Over the last decade, there has been an increase in the application of pulsed field gradient nuclear magnetic resonance (PFG NMR) to characterize food materials. In this work, PFG NMR was used to examine the impact of chemical modification on properties of solubilized high amylose starches obtained from heated (121 °C for 15 min) starch suspensions (0.5% w/w). The starches examined were high amylose maize starch (HAMS) and high amylose maize starch chemically modified with acetate (HAMSA), propionate (HAMSP) and butyrate (HAMSB) at degree of substitution (DS) of 0.2. The hydrothermal treatment solubilized 3.36–4.96% of the starch in all samples, corresponding to concentrations of 10.36–10.91 μM on glucose equivalents basis. The hydrodynamic radii of the starches were 30 Å (HAMS), 45 Å (HAMSB), 60–70 Å (HAMSA & HAMSP). Contrary to expectations, the radii did not increase with the molecular weight of the fatty acid attached to the starch. Rather, the trend in the observed hydrodynamic radii was related to the physical organization of the starch molecules in higher DS granular dried starch (DS = 0.32–0.40) as observed by others using X-ray diffraction and small angle X-ray scattering, suggesting the preservation of the nano-structure of starch molecules upon solubilization. Upon storage (7 days at 25 °C), there was retrogradation of HAMS but not of modified HAMS. Given the correlation between retrogradation and food spoilage, the inhibition of retrogradation in the soluble fraction of modified HAMS may increase the stability of starch containing foods.

Diffusion of ethane and ethylene in carbon molecular sieve membranes by pulsed field gradient NMR

Carbon molecular sieve (CMS) membranes are promising new materials which have potential applications in light paraffin/olefin gas separations. Despite the importance of mass transport in these materials there have been no reported diffusion studies of C2 (or larger) hydrocarbons in CMS membranes using microscopic techniques. In this work, a pulsed field gradient (PFG) NMR technique employing high magnetic field and large magnetic field gradients enabled the measurement of microscopic self-diffusion of ethane and ethylene in selected CMS membranes. For the studied Matrimid CMS membranes, the results of PFG NMR diffusion studies are compared with corresponding data obtained from macroscopic permeation measurements reported in the literature. It was found that although the ratios of ethane and ethylene diffusivities measured by these two techniques were the same within the experimental uncertainty, the diffusivities obtained by PFG NMR were several times larger than those obtained from permeation. The reasons for such difference are discussed.

Effects of a polar amino acid substitution on helix formation and aggregate size along the detergent-induced peptide folding pathway

Membrane proteins constitute a significant fraction of the proteome and are important drug targets. While the transmembrane (TM) segments of these proteins are primarily composed of hydrophobic residues, the inclusion of polar residues—either naturally occurring or as a consequence of a disease-related mutation—places a significant folding burden in this environment, potentially impacting bilayer insertion and/or association of neighboring TM helices. Here we investigate the role of an anionic detergent, sodium dodecylsulfate (SDS), and a zwitterionic detergent, dodecylphosphocholine (DPC), in the folding process, and the effects induced by a single polar substitution, on structure and topology of model α-helical TM segments. The peptides, represented by KK-YAAAIAAIAWAXAAIAAAIAA-KKK-NH2, where X is I or N, are designed with high aqueous solubilities, through poly-lysine tags. Circular dichroism (CD) and NMR were used to monitor peptide secondary structure and diffusional mobility of both peptide and the detergent hosts. For both peptides, SDS binding commenced at a concentration below its CMC, due to Coulombic attraction of anionic SDS to cationic Lys residues. Increasing SDS binding correlated with increasing peptide helicity. Pulsed field gradient (PFG) NMR diffusion measurements revealed that the Asn-containing peptide bound four fewer detergent molecules, corresponding to ca. 20% less SDS than bound by the Ile peptide. Conversely, zwitterionic DPC binding to either peptide was not observed until the DPC concentration approached its CMC. Our findings confirm quantitatively that a single polar residue within a TM segment may have a significant influence on its local membrane environment.

Identification of Multiple Diffusion Rates in Mixed Solvent Anion Exchange Membranes Using High Resolution MAS NMR

High resolution magic angle spinning (HRMAS) 1H NMR in combination with 2D exchange NOESY and pulsed field gradient (PFG) NMR diffusion experiments have been used to characterize 1 N methanol swollen polymer anion exchange membranes (AEM) presently being developed for alkaline fuel cells. Standard static 1H NMR experiments on these materials have proven unsuccessful due to severe signal broadening. New experimental methods for increased resolution are needed to determine distinct solvent environments and transport properties. Using HRMAS NMR, resonances from water and methanol in both a free (bulk-like) environment and membrane-associated environment within the AEM were observed. 1H HRMAS PFG NMR experiments identified different molecular diffusion environments in the solvent, while 1H 2D NOESY exchange NMR experiments confirmed spatial contacts between membrane-associated species and the membrane. These results demonstrate that 1H HRMAS is an ideal technique for the characterization of individual environments and diffusion rates in polymer membranes with mixed solvent systems.

X-Nuclei NMR Self-Diffusion Studies in Mesoporous Silica Foam and Microporous MOF CuBTC.

A standard X-observe NMR probe was equipped with a z-gradient coil to enable high-sensitivity pulsed field gradient NMR diffusion studies of and cations of aqueous salt solutions in a high-porosity mesocellular silica foam (MCF) and of adsorbed in metal-organic frameworks (MOF). The coil design and the necessary probe modifications, which yield pulsed field gradients of up to , are introduced. The system was calibrated at resonance frequency and successfully applied for diffusion studies at , , and frequencies. Significant reductions of the diffusivities of the cations in and solution introduced into MCFs are observed. By comparison of the diffusion behavior with the bulk solutions, a tortuosity of the silica foam of was derived. Single component self-diffusion of and (measured by NMR) as well as self-diffusion of the individual components in / mixtures was studied in the MOF CuBTC. The experimental results confirm high mobilities of the adsorbed gases and trends for diffusion separation factors predicted by MD simulations.

Diffusion NMR and bicelle morphology

This minireview focuses on diffusion NMR studies in bicelles. Following a discourse on diffusion fundamentals, and a comparative overview of fluorescence and NMR-based techniques for measuring diffusion, the pulsed field gradient (PFG) NMR diffusion method is introduced, emphasizing its specific advantages and limitations when applied to diffusion measurements in macroscopically oriented lamellar systems such as magnetically aligned bicelles. The utility of PFG NMR diffusion measurements in bicellar model membrane systems for examining lateral diffusion of membrane-bound molecular species is demonstrated, along with certain features of lateral diffusion that such studies illuminate. Further, those aspects of bicelle morphology that have been resolved using PFG NMR diffusion studies of various molecular weight soluble polymeric species are reviewed. The discussion concludes with an outline of future prospects for diffusion NMR studies in bicelles.

Temperature Driven Annealing of Perforations in Bicellar Model Membranes

Bicellar model membranes composed of 1,2-dimyristoylphosphatidylcholine (DMPC) and 1,2-dihexanoylphosphatidylcholine (DHPC), with a DMPC/DHPC molar ratio of 5, and doped with the negatively charged lipid 1,2-dimyristoylphosphatidylglycerol (DMPG), at DMPG/DMPC molar ratios of 0.02 or 0.1, were examined using small angle neutron scattering (SANS), (31)P NMR, and (1)H pulsed field gradient (PFG) diffusion NMR with the goal of understanding temperature effects on the DHPC-dependent perforations in these self-assembled membrane mimetics. Over the temperature range studied via SANS (300-330 K), these bicellar lipid mixtures exhibited a well-ordered lamellar phase. The interlamellar spacing d increased with increasing temperature, in direct contrast to the decrease in d observed upon increasing temperature with otherwise identical lipid mixtures lacking DHPC. (31)P NMR measurements on magnetically aligned bicellar mixtures of identical composition indicated a progressive migration of DHPC from regions of high curvature into planar regions with increasing temperature, and in accord with the "mixed bicelle model" (Triba, M. N.; Warschawski, D. E.; Devaux, P. E. Biophys. J.2005, 88, 1887-1901). Parallel PFG diffusion NMR measurements of transbilayer water diffusion, where the observed diffusion is dependent on the fractional surface area of lamellar perforations, showed that transbilayer water diffusion decreased with increasing temperature. A model is proposed consistent with the SANS, (31)P NMR, and PFG diffusion NMR data, wherein increasing temperature drives the progressive migration of DHPC out of high-curvature regions, consequently decreasing the fractional volume of lamellar perforations, so that water occupying these perforations redistributes into the interlamellar volume, thereby increasing the interlamellar spacing.