NMR Diffusion Studies Research Articles

Ionosome single entity electrochemical detection at a micro water/alkylphosphonium ionic liquid interface

Ionic liquids (ILs) are composed of molecularly large organic ions that exist as supramolecular ion aggregates or contact ion pairs which contributes to their catalytic nature and control of metal nanoparticle growth. However, additions of small organic molecules may disrupt these aggregates. Herein, single entity electrochemistry (SEE) has been used to probe the formation of solvent microchannels that form in between IL and ion aggregates through the electrogeneration of ionosomes, i.e., water/ion-in-IL nanoclusters, at a micro water/IL (w|IL) immiscible interface. A concomitant increase in ionosome size was observed with increasing molecular solvent additions; however, diffusion NMR studies indicate that IL-ion aggregates do not shrink in size until a critical solvent level is achieved at ∼ 25% v/v solvent/IL indicating a ‘solvent tolerance’ limit. Thus, diffusion NMR and SEE paint two complementary pictures of the IL supramolecular system under solvent addition.

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 studies of adsorption and diffusion in porous carbonaceous materials

Porous carbonaceous materials have many important industrial applications including energy storage, water purification, and adsorption of volatile organic compounds. Most of their applications rely upon the adsorption of molecules or ions within the interior pore volume of the carbon particles. Understanding the behaviour and properties of adsorbate species on the molecular level is therefore key for optimising porous carbon materials, but this is very challenging owing to the complexity of the disordered carbon structure and the presence of multiple phases in the system. In recent years, NMR spectroscopy has emerged as one of the few experimental techniques that can resolve adsorbed species from those outside the pore network. Adsorbed, or “in-pore” species are shielded with respect to their free (or “ex-pore”) counterparts. This shielding effect arises primarily due to ring currents in the carbon structure in the presence of a magnetic field, such that the observed chemical shift differences upon adsorption are independent of the observed nucleus to a first approximation. Theoretical modelling has played an important role in rationalising and explaining these experimental observations. Together, experiments and simulations have enabled a large amount of information to be gained on the adsorption and diffusion of adsorbed species, as well as on the structural and magnetic properties of the porous carbon adsorbent. Here, we review the methodological developments and applications of NMR spectroscopy and related modelling in this field, and provide perspectives on possible future applications and research directions.

Synthesis of Cannabinoids: "In Water" and "On Water" Approaches: Influence of SDS Micelles.

We have proven that the biomimetic-like synthesis of cannabinoids from citral and the corresponding phenolic counterpart may well be carried out using water as a solvent. The influence of different additives such as surfactants was also analyzed. Rationalization of the reaction mode and regiochemistry of the processes were provided in terms of “on water” and “in water” reactions. The same reactions were conducted in organic media using Ga(III) salts as catalysts. Worthy of being underlined, an unprecedented formal [2+2+2] process was found to occur between two citral molecules and the corresponding phenolic species in both aqueous and organic environments. Computational studies were performed in order to gain a comprehensive mechanistic and energetic understanding of the different steps of this singular process. Finally, the influence of SDS micelles in the chemical behavior of olivetol and citral was also pursued using PGSE diffusion and NOESY NMR studies. These data permitted to tentatively propose the existence of a mixed micelle between olivetol and SDS assemblies.

Diffusion NMR and Rheology Study of a Model Polymer and a Disordered Protein in the Presence of Bacterial Cell Lysate Crowders

The intracellular milieu has a macromolecular concentration up to 400 mg/ml, making the environment crowded and heterogeneous. Macromolecular crowding has been traditionally studied in artificial crowders like Ficoll and Dextran. Macromolecular crowding can modify processes such as protein- protein interactions, protein folding, ligand binding and aggregation. It is not clear if the effects of artificial crowders on such phenomena are the same as the effect of biological crowders. Biological crowders, such as bacterial cell lysate, are heterogeneous biomolecules with different sizes, shapes and charges.

Locking mixed-lineage kinase domain-like protein in its auto-inhibited state prevents necroptosis.

As an alternative pathway of controlled cell death, necroptosis can be triggered by tumor necrosis factor via the kinases RIPK1/RIPK3 and the effector protein mixed-lineage kinase domain-like protein (MLKL). Upon activation, MLKL oligomerizes and integrates into the plasma membrane via its executioner domain. Here, we present the X-ray and NMR costructures of the human MLKL executioner domain covalently bound via Cys86 to a xanthine class inhibitor. The structures reveal that the compound stabilizes the interaction between the auto-inhibitory brace helix α6 and the four-helix bundle by stacking to Phe148. An NMR-based functional assay observing the conformation of this helix showed that the F148A mutant is unresponsive to the compound, providing further evidence for the importance of this interaction. Real-time and diffusion NMR studies demonstrate that xanthine derivatives inhibit MLKL oligomerization. Finally, we show that the other well-known MLKL inhibitor Necrosulfonamide, which also covalently modifies Cys86, must employ a different mode of action.

Anomalously High Fluorine Mobility in Tysonite-Like LaF3:ScF3 Nanocrystals: NMR Diffusion Data

Nanosized La0.93Sc0.07F3 superionic conductor with tysonite structure was obtained at the gas–solution interface after interaction of aqueous salt solution with gaseous HF. NMR diffusion studies show that homovalent substitution of La3+ by Sc3+ with a smaller ionic radius leads to around four orders of magnitude faster fluorine diffusion as compared with crystalline LaF3 and faster as in all previously studied nanosized LaF3 and heterovalent-doped nanosized La0.95Sr0.05F2.95. The homovalent doping is a new route to improve the conductivity of tysonite-structured nanomaterials.

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.

Hydrogen Bonding in a l-Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation.

This paper reports on synthesis, acid–base properties, and self-structuring in water of a chiral polyamidoamino acid, M-l-Gln, obtained from the polyaddition of N,N′-methylenebisacrylamide with l-glutamine, with the potential of establishing hydrogen bonds through its prim-amide pendants. The M-l-Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents. The NMR diffusion studies were consistent with a population of unimolecular nanoparticles thus excluding aggregation. The M-l-Gln had the highest molecular weight and hydrodynamic radius among all polyamidoamino acids described. Possibly, transient hydrogen bonds between l-glutamine molecules and M-l-Gln growing chains facilitated the polyaddition reaction. Theoretical modeling showed that M-l-Gln assumed pH-dependent self-ordered coil conformations with main chain transoid arrangements reminiscent of the protein hairpin motif owing to intramolecular dipole moments and hydrogen bonds. The latter were most numerous at the isoelectric point (pH 4.5), where they mainly involved even topologically distant main chain amide N–H and side chain amide C=O brought to proximity by structuring. Hydrogen bonds at pH 4.5 were also suggested by variable temperature NMR. The 2D NOESY experiments at pH 4.5 confirmed the formation of compact structures through the analysis of the main chain/side chain hydrogen contacts, in line with MD simulations.

Diffusion NMR Studies on the Self-Aggregation of Ru-Arene CAP Complexes: Evidence for the Formation of H-Bonded Dicationic Species in Acetonitrile

The self-aggregation of neutral [RuCl2(η6-p-cymene)(CAP)] (2; p-cymene = 1-methyl-4-(propan-2-yl)benzene) and ionic [RuCl(η6-p-cymene)(L)(CAP)](PF6) (3, L = CAP; 4, L = MeCN) and [RuCl2(η6-p-cymene...

NMR diffusion studies of proton-exchange membranes in wide temperature range

The diffusion coefficients in proton-exchange perfluorosulfonated membranes fabricated by different techniques have been analyzed in the temperature range from 200 K to 300 K using NMR diffusometry in a static magnetic gradient field. The influence of the water content as well as the effects of the membrane thickness and the side-chain length on the diffusion coefficient was analyzed. It is found that the fabrication by the extrusion cast method leads to faster diffusion as compared to the solution cast fabrication method. Shorter side chains are also preferable for faster diffusion. Both the decrease of the temperature and the water content leads to a reduced diffusion coefficient, affecting the transport micromechanism in a similar way by increasing the role of the water on the pore walls with respect to proton transport. The model of confined water in Nafion pores has been applied to analyze the results. It is proposed that both conductivity and diffusion at low temperatures are determined by protonic transport of the surface water via bond defects in contrast to the bulk water or ice, where the ionic defects are responsible for the mass transport.

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...

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.

Reaction Chemistry of Silver(I) Trifluoromethanesulfonate Complexes of Nitrogen-Confused C-Scorpionates.

Two new C-scorpionate ligands with a bis(3,5-dimethylpyrazol-1-yl)methyl group bound to the 3 position of either an N-tosyl (TsL*) or an N-H pyrazole (HL*) ring have been prepared. The silver(I) complexes of these new ligands and the two previously reported analogous ligands with unsubstituted bis(pyrazol-1-yl)methyl groups (TsL and HL) in both 1:1 and 2:1 ligand/metal ratios were investigated to explore the effects of ligand sterics on their physical and chemical properties. The structurally characterized derivatives of the type [Ag(L)2](OTf) are four-coordinate, where the confused pyrazolyl is not bound to the metal. On the other hand, three 1:1 complexes [Ag(L)](OTf) had all pyrazolyls bound, while the μ-κ1,κ1-TsL derivative had an unbound confused pyrazolyl. The molecularity of the latter four ranged from polymeric to dimeric to monomeric in the solid with increasing steric bulk of the ligand. The utility of these complexes in stoichiometric ligand-transfer reactions and in styrene aziridination was demonstrated. Thus, tricarbonylmanganese(I) complexes were prepared as kinetically inert models for comparative solution diffusion NMR studies. Also, [Fe(HL)2](OTf)2 was prepared for similar reasons and to compare the effects of anion on spin-crossover properties.

Realization of a stable, monodisperse water-in-oil droplet system with micro-scale and nano-scale confinement for tandem microscopy and diffusion NMR studies.

In this work we generate stable and monodisperse water-in-oil emulsions using a co-flowing geometry that produced droplet sizes between 13 μm and 250 μm. The drops survived transfer to NMR tubes and were stable for at least 26 hours, enabling the performance of pulsed-field-gradient NMR experiments in addition to microscopy. The drops sizes achieved as a function of flow rate agree well with a simple model for droplet generation: this yields a precise measure of the interfacial tension. The design of a cell mimetic environment with nano-scale confinement has also been demonstrated with diffusion measurements on macromolecules (PEG and Ficoll70) within droplets that are further structured internally using agarose gel networks. Containing the agarose gel in droplets appears to provide very reproducible and homogeneous network environments, enabling quantitative agreement of Ficoll70 dynamics with a theoretical model, with no fit parameters, and, with PEG, yielding a systematic polymer-size dependent slowing down in the network. This is in contrast with bulk agarose, where identical macromolecular diffusion measurements indicate the presence of heterogeneities with water pockets.

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.

C-Terminal Modification and Multimerization Increase the Efficacy of a Proline-Rich Antimicrobial Peptide.

Two series of branched tetramers of the proline-rich antimicrobial peptide (PrAMP), Chex1-Arg20, were prepared to improve antibacterial selectivity and potency against a panel of Gram-negative nosocomial pathogens including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. First, tetramerization was achieved by dithiomaleimide (DTM) conjugation of two C-terminal-cysteine bearing dimers that also incorporated C-terminal peptide chemical modification. DTM-linked tetrameric peptides containing a C-terminal hydrazide moiety on each dimer exhibited highly potent activities in the minimum inhibitory concentration (MIC) range of 0.49-2.33 μm. A second series of tetrameric analogues with C-terminal hydrazide modification was prepared by using alternative conjugation linkers including trans-1,4-dibromo-2-butene, α,α'-dibromo-p-xylene, or 6-bismaleimidohexane to determine the effect of length on activity. Each displayed potent and broadened activity against Gram-negative nosocomial pathogens, particularly the butene-linked tetrameric hydrazide. Remarkably, the greatest MIC activity is against P. aeruginosa (0.77 μm/8 μg mL-1 ) where the monomer is inactive. None of these peptides showed any cytotoxicity to mammalian cells up to 25 times the MIC. A diffusion NMR study of the tetrameric hydrazides showed that the more active antibacterial analogues were those with a more compact structure having smaller hydrodynamic radii. The results show that C-terminal PrAMP hydrazidation together with its rational tetramerization is an effective means for increasing both diversity and potency of PrAMP action.

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.

PIM-1 as a Solution-Processable "Molecular Basket" for CO2 Capture from Dilute Sources.

Rising atmospheric CO2 levels have triggered recent research into the science of amine materials supported on hard, porous materials such as mesoporous silica or alumina. While such materials can give high CO2 uptakes and good sorption kinetics, they are difficult to utilize in practical applications due to difficulty in contacting large volumes of CO2-laden gases with powder materials without significant pressure drops or sorbent attrition. Here, we describe a simple approach based on the impregnation of a permanently microporous polymer, PIM-1, with poly(ethylene imine) (PEI), removing the need for use of the hard oxide. PEI/PIM-1 composites demonstrate comparable performance to more traditionally studied oxide sorbents, with the benefit that PIM-1 is soluble in common solvents, making it eminently more viable for processing into morphologies that can facilitate heat and mass transfer and fabrication into low pressure drop contactors. In addition to adsorption studies performed on a variety of PEI/PIM-1 architectures, spin diffusion NMR studies were performed to suggest that PEI is well-dispersed within the PIM-1, allowing for rapid CO2 adsorption.

Pulsed-field gradient 1H NMR study of diffusion and self-aggregation of long-chain imidazolium-based ionic liquids

Diffusion and self-aggregation (micellization) processes of the neat 1-decyl-3-methyl-imidazolium chloride ([C10mim][Cl]) and its aqueous solutions have been studied using pulsed-field gradient 1H NMR. Different from many RTILs, whose temperature dependencies of the diffusion coefficient in log D vs. 1/T plot exhibit curved profiles and thus obey the Vogel–Fulcher–Tammann (VFT) equation, those in the neat [C10mim][Cl] have been found to be perfect Arrhenius-type. This finding has been discussed in terms of the classification of compounds into ‘fragile’-, ‘intermediate’- and ‘strong glass formers’. The Arrhenius-type behavior can be explained by the presence of the long and flexible alkyl chains, which soften the system making it more plastic and less ‘fragile’. The obtained activation energy values can be compared with those available in the literature for other RTILs and for some long-chain fatty acids (e.g. heptadecanoic (C17) and nonadecanoic (C19)) close to the melting point in the orientationally disordered solid phases. It can be assumed that the diffusion processes in the neat long-chain RTILs, similar to other long-chain molecular systems, go through the vacancies and the boundaries of highly dynamic mesoscopic structures. The critical aggregation concentration and the aggregation number have been determined from the dependence of diffusion coefficient on concentration in an aqueous solution.