1H Relaxation Research Articles

Cl- and Na+ ions binding in slag and fly ash cement paste during early hydration as studied by 1H, 35Cl and 23Na NMR

Lacking effective and in particular direct methods, the study on Cl- and Na+ ion binding during hydration has rarely been reported. In this study, a specially developed Nuclear Magnetic Resonance setup was employed to study the Cl- and Na+ ion binding of cement pastes during hydration. Influence factors, such as slag and fly ash replacement, on the 1H, 35Cl and 23Na relaxation of the cement paste made with 1 mol/L NaCl solutions were investigated. It was found that the increase of slag in the cement gives rise to bigger pores during hydration, and the fly ash resulted in less water being consumed. The Cl- signals would first be stable then gradually decrease as a function of time. The slag in cement has minor impacts on the Cl- ions binding, and the fly ash replacement in the cement would result in less Cl- ions binding during the hydration. Results also suggest that the slag could result in later Na+ binding, and the fly ash in the cement will significantly reduce the Na+ binding. Besides, the Cl- ions will bind earlier compared to the Na+ ions, which is probably related to the characteristics of the hydrates. The normalized 35Cl and 23Na signal intensity, in general, decrease with water consumption reflecting the hydration. Furthermore, the early formed hydrates would consume relatively less water but bind more Cl- and Na- ions.

Polar/apolar domains' dynamics in alkylimidazolium ionic liquids unveiled by the dual receiver NMR 1H and 19F relaxation experiment

The dual receiver 1H/19F inversion-recovery NMR method is applied to measure simultaneously the spin-lattice relaxation times, T1, of both cation and anion forming ionic liquid (ILs) materials. Two representative classes of ILs comprising 1-alkyl-3-methylimidazolium [CnMIm]+ (n = 2, 12) as cation and bis(trifluoromethylsulfonyl)imide [TFSI]− or tetrafluoroborate [BF4]− as anions have been considered. The experimental data, acquired on a wide range of temperature (278–333 K), have been analysed according to the Bloembergen, Purcell, and Pound model and provide the rotational dynamic parameters, such as the activation energy and the correlation time τc of the rotational segmental motion. The overall dynamic behaviour is dictated by the length of the alkyl chain and the capability of the anion to disrupt or stabilize the apolar domain structure.

Probing relaxation models by means of Fast Field-Cycling relaxometry, NMR spectroscopy and molecular dynamics simulations: Detailed insight into the translational and rotational dynamics of a protic ionic liquid

A combination of temperature dependent Fast Field-Cycling (FFC) relaxometry and high-resolution NMR spectroscopy provides more than five orders of magnitude in frequency range for studying translational and rotational dynamics of ionic liquids. However, to make use of this broad frequency range, certain requirements have to be met: The viscosity of the liquid has to be of the right order of magnitude, and the material has to exhibit a sufficiently broad liquid range. In addition, NMR sensitive nuclei have to be present (ideally) on both, cation and anion, and appropriate relaxation models properly describing the molecular dynamics have to be available. For the latter, Molecular Dynamics (MD) simulations are ideally suited to suggest meaningful relaxation models. In this study we employ the protic ionic liquid triethylammonium bis(trifluoromethylsulfonyl)-imide [TEA][NTf2] as model compound to gain insight into details of the molecular dynamical processes. By addressing different NMR sensitive nuclei on both ions, 1H nuclei on the triethylammonium cation, and 19F on the NTf2 anion, we are able to obtain translational dynamics as well as rotational dynamics for both species at the same time. The obtained temperature dependent translatoric diffusion coefficients are consistent with our MD simulations, and are found to be in agreement with data reported in the literature. In addition, two types of NMR relaxation processes are employed to investigate the intramolecular relaxation: (1) dipolar relaxation at low frequencies (employing FFC) addressing 1H and 19F nuclei, and (2) quadrupolar relaxation at high frequencies addressing 2H nuclei. In near quantitative agreement with MD simulations, we show that both, dipolar relaxation obtained via FFC and quadrupolar relaxation obtained via high-field NMR are leading to consistent rotational correlation times, suggesting that the rotational motion of the cation is dominantly isotropic. Hence, the intramolecular 1H relaxation rate of the cation determined via FFC can be appropriately expressed by a single rotational correlation time, compatible with the Bloembergen Purcell Pound (BPP) approach. MD simulations of the NTf2 anion, however, suggest that its reorientational dynamics is strongly anisotropic. Consequently, the proper description of the intramolecular 19F relaxation rate of the anion requires a more complex model beyond the BPP approach employing at least two correlation times: By taking internal rotation of the CF3 groups into account, we are able to determine correlation times compatible with our MD simulations.

Slow dynamics of solid proteins – Nuclear magnetic resonance relaxometry versus dielectric spectroscopy

1H Nuclear Magnetic Resonance (NMR) relaxometry and Dielectric Spectroscopy (DS) have been exploited to investigate the dynamics of solid proteins. The experiments have been carried out in the frequency range of about 10 kHz-40 MHz for NMR relaxometry and 10−2Hz-20 MHz for DS. The data sets have been analyzed in terms of theoretical models allowing for a comparison of the correlation times revealed by NMR relaxometry and DS. The 1H spin–lattice relaxation profiles have been decomposed into relaxation contributions associated with 1H–1H and 1H-14N dipole – dipole interactions. The 1H–1H relaxation contribution has been interpreted in terms of three dynamical processes of time scales of 10−6s, 10−7s and 10−8s. It has turned out that the correlation times do not differ much among proteins and they are only weakly dependent on temperature. The analysis of DS relaxation spectra has also revealed three motional processes characterized by correlation times that considerably depend on temperature in contrast to those obtained from the 1H relaxation. This finding suggest that for solid proteins there is a contribution to the 1H spin–lattice relaxation associated with a kind of motion that is not probed in DS as it does not lead to a reorientation of the electric dipole moment.

Stabilization of Active Site Dynamics Leads to Increased Activity with 3'-Azido-3'-deoxythymidine Monophosphate for F105Y Mutant Human Thymidylate Kinase.

Thymidylate kinases are essential enzymes with roles in DNA synthesis and repair and have been the target of drug development for antimalarials, antifungals, HIV treatment, and cancer therapeutics. Human thymidylate kinase (hTMPK) conversion of the anti-HIV prodrug 3′-azido-3′-deoxythymidine (AZT or zidovudine) monophosphate to diphosphate is the rate-limiting step in the activation of AZT. A point mutant (F105Y) has been previously reported with significantly increased activity for the monophosphate form of the drug [3′-azidothymidine-5′-monophosphate (AZTMP)]. Using solution nuclear magnetic resonance (NMR) techniques, we show that while the wild-type (WT) and F105Y hTMPK adopt the same structure in solution, significant changes in dynamics may explain their different activities toward TMP and AZTMP. 13C spin-relaxation measurements show that there is little change in dynamics on the ps to ns time scale. In contrast, methyl 1H relaxation dispersion shows that AZTMP alters adenosine nucleotide handling in the WT protein but not in the mutant. Additionally, the F105Y mutant has reduced conformational flexibility, leading to an increase in affinity for the product ADP and a slower rate of phosphorylation of TMP. The dynamics at the catalytic center for F105Y bound to AZTMP are tuned to the same frequency as WT bound to TMP, which may explain the mutant’s catalytic efficiency toward the prodrug.

Understanding Li‐Ion Dynamics in Lithium Hydroxychloride (Li2OHCl) Solid State Electrolyte via Addressing the Role of Protons

AbstractLow‐melting‐point solid‐state electrolytes (SSE) are critically important for low‐cost manufacturing of all‐solid‐state batteries. Lithium hydroxychloride (Li2OHCl) is a promising material within the SSE domain due to its low melting point (mp < 300 °C), cheap ingredients (Li, H, O, and Cl), and rapid synthesis. Another unique feature of this compound is the presence of Li vacancies and rotating hydroxyl groups which promote Li‐ion diffusion, yet the role of the protons in the ion transport remains poorly understood. To examine lithium and proton dynamics, a set of solid‐state NMR experiments are conducted, such as magic‐angle spinning 7Li NMR, static 7Li and 1H NMR, and spin‐lattice T1(7Li)/T1(1H) relaxation experiments. It is determined that only Li+ contributes to long‐range ion transport, while H+ dynamics is constrained to an incomplete isotropic rotation of the OH group. The results uncover detailed mechanistic understanding of the ion transport in Li2OHCl. It is shown that two distinct phases of ionic motions appear at low and elevated temperatures, and that the rotation of the OH group controls Li+ and H+ dynamics in both phases. The model based on the NMR experiments is fully consistent with crystallographic information, ionic conductivity measurements, and Born–Oppenheimer molecular dynamic simulations.

NMR-Responsive Paramagnetic [M-EDTA] (M = Fe3+, Mn2+, Cu2+) Complexes to Differentiate T2-Distribution Signals of Crude Oil and Brine

Nuclear magnetic resonance (NMR) well logging tools are being commercially utilized for the characterization of various fluids confined within reservoir rocks. Conventional NMR T2-distribution measurements are unable to quantify the actual fractions of crude oil and brine simultaneously present in the reservoir rocks. Herein, we reported NMR-responsive paramagnetic [M-EDTA] (M = Fe3+, Mn2+, Cu2+) complexes having the capability to differentiate NMR T2-distribution signals coming from crude oil and brine by accelerating the water (1H) relaxation. The formation of these [Fe-EDTA]−, [Mn-EDTA]2–, and [Cu-EDTA]2– complexes was explored by UV–visible spectroscopy, and their chemical stability in brine solution was monitored by measuring the change in percent transmittance and backscattering intensities with time. Spin–spin (T2) relaxation signals and T2-distribution spectra of various carbonate and sand packs were recorded. The separation of NMR T2-distribution signals was achieved using the optimized concentra...

Dynamics of Solid Proteins by Means of Nuclear Magnetic Resonance Relaxometry.

1H Nuclear magnetic resonance (NMR) relaxometry was exploited to investigate the dynamics of solid proteins. The relaxation experiments were performed at 37 °C over a broad frequency range, from approximately 10 kHz to 40 MHz. Two relaxation contributions to the overall 1H spin–lattice relaxation were revealed; they were associated with 1H–1H and 1H–14N magnetic dipole–dipole interactions, respectively. The 1H–1H relaxation contribution was interpreted in terms of three dynamical processes occurring on timescales of 10−6 s, 10−7 s, and 10−8 s, respectively. The 1H–14N relaxation contribution shows quadrupole relaxation enhancement effects. A thorough analysis of the data was performed revealing similarities in the protein dynamics, despite their different structures. Among several parameters characterizing the protein dynamics and structure (e.g., electric field gradient tensor at the position of 14N nuclei), the orientation of the 1H–14N dipole–dipole axis, with respect to the principal axis system of the electric field gradient, was determined, showing that, for lysozyme, it was considerably different than for the other proteins. Moreover, the validity range of a closed form expression describing the 1H–14N relaxation contribution was determined by a comparison with a general approach based on the stochastic Liouville equation.

Rotamer Jumps, Proton Exchange, and Amine Inversion Dynamics of Dimethylated Lysine Residues in Proteins Resolved by pH-Dependent 1H and 13C NMR Relaxation Dispersion.

Post-translational methylation of lysine side chains is of great importance for protein regulation, including epigenetic control. Here, we present specific 13CHD2 labeling of dimethylated lysines as a sensitive probe of the structure, interactions, and dynamics of these groups, and outline a theoretical and experimental framework for analyzing their conformational dynamics using 1H and 13C CPMG relaxation dispersion experiments. Dimethylated lysine side chains in calcium-loaded calmodulin show a marked pH dependence of their Carr-Purcell-Meiboom-Gill (CPMG) dispersion profiles, indicating complex exchange behavior. Combined analysis of 1H and 13C CPMG relaxation dispersions requires consideration of 12-state correlated exchange of the two methyl groups due to circular three-state rotamer jumps around the Cε-Nζ axis combined with proton exchange and amine inversion. Taking into account a number of fundamental constraints, the exchange model can be reduced to include only three fitted parameters, namely, the geometric average of the rotamer-jump rate constants, the rate constant of deprotonation of Nζ, and the chemical shift difference between the trans and gauge positions of the 13C or 1H nuclei. The pH dependence indicates that protonation of the end group dramatically slows down rotamer exchange for some lysine residues, whereas deprotonation leads to rapid amine inversion coupled with rotamer scrambling. The observed variation among residues in their exchange behavior appears to depend on the structural environment of the side chain. Understanding this type of exchange process is critical to correctly interpreting NMR spectra of methylated lysine side chains. The exchange model presented here forms the basis for studying the structure and dynamics of epigenetically modified lysine side chains and perturbations caused by changes in pH or interactions with target proteins.

Estimation of the magnitude of quadrupole relaxation enhancement in the context of magnetic resonance imaging contrast.

Magnetic Resonance Imaging (MRI) is one of the most powerful diagnostic tools providing maps of 1H relaxation times of human bodies. The method needs, however, a contrast mechanism to enlarge the difference in the relaxation times between healthy and pathological tissues. In this work, we discuss the potential of a novel contrast mechanism for MRI based on Quadrupole Relaxation Enhancement (QRE) and estimate the achievable value of QRE under the most favorable conditions. It has turned out that the theoretically possible enhancement factors are smaller than those of typical paramagnetic contrast agents, but in turn, the field-selectivity of QRE-based agents makes them extremely sensitive to subtle changes of the electric field gradient in the tissue. So far, QRE has been observed for solids (in most cases for 14N) as a result of very slow dynamics and anisotropic spin interactions, believed to be necessary for QRE to appear. We show the first evidence that QRE can be achieved in solutions of compounds containing a high spin nucleus (209Bi) as the quadrupole element. The finding of QRE in a liquid state is explained in terms of spin relaxation theory based on the stochastic Liouville equation. The results confirm the relaxation theory and motivate further exploration of the potential of QRE for MRI.

Structure of Superabsorbent Polyacrylate Hydrogels and Dynamics of Counterions by Nuclear Magnetic Resonance

AbstractPolyacrylate hydrogels PAAM (M = 7Li+, 23Na+, 39K+, 87Rb+, and 133Cs+) are synthesized by free‐radical copolymerization and are studied by Nuclear Magnetic Resonance (NMR) over wide time and length scales to get an insight into the polymer network structure and the dynamics of alkali ions and water. 1H double‐quantum NMR (1H DQ‐NMR) indicates that neutralization by different alkali ions influences the polymer structure in swollen PAAM hydrogels. Relaxation rates of alkali ions are found to be dominated by quadrupolar relaxation. 1H relaxation varies with the chain fraction obtained from 1H DQ‐NMR. Pulsed field gradient NMR reveals diffusion coefficients of alkali ions and water for different swelling degrees. Network structure and dynamics as well as the interactions between water, alkali ions, and polymer chains are discussed.

Mechanistic Insights into Microsecond Time-Scale Motion of Solid Proteins Using Complementary 15N and 1H Relaxation Dispersion Techniques.

NMR relaxation dispersion methods provide a holistic way to observe microsecond time-scale protein backbone motion both in solution and in the solid state. Different nuclei (1H and 15N) and different relaxation dispersion techniques (Bloch-McConnell and near-rotary-resonance) give complementary information about the amplitudes and time scales of the conformational dynamics and provide comprehensive insights into the mechanistic details of the structural rearrangements. In this paper, we exemplify the benefits of the combination of various solution- and solid-state relaxation dispersion methods on a microcrystalline protein (α-spectrin SH3 domain), for which we are able to identify and model the functionally relevant conformational rearrangements around the ligand recognition loop occurring on multiple microsecond time scales. The observed loop motions suggest that the SH3 domain exists in a binding-competent conformation in dynamic equilibrium with a sterically impaired ground-state conformation both in solution and in crystalline form. This inherent plasticity between the interconverting macrostates is compatible with a conformational-preselection model and provides new insights into the recognition mechanisms of SH3 domains.

Monitoring solvent dynamics and ion associations in the formation of cubic octamer polyanion in tetramethylammonium silicate solutions.

NMR methods were utilized to monitor the in situ structural and dynamic changes of various species in highly alkaline tetramethylammonium (TMA) silicate solutions. Quantitative 29Si NMR, 1H, 2H, and 17O relaxation NMR, and 1H and 29Si diffusion NMR of silicates, TMA, H2O and D2O demonstrate that the growth of the cubic octamer Q38 is accompanied by reduced water mobility and increasing TMA coordination number per Q38, which reaches an equilibrium value of 4.5 at 15 °C. Temperature-dependent measurements further reveal that the increased control over speciation by TMA at lower temperatures results from the more stable ion associations via slower solvent motions.

Solid-state 23Na NMR spectroscopy studies of ordered and disordered cellulose nanocrystal films

Cellulose nanocrystal films with either disordered or chiral nematic structures of varying helical pitch were investigated using 23Na solid-state nuclear magnetic resonance (NMR) spectroscopy. Spin lattice relaxation of 1H correlated with 23Na analyzed by indirect observation using polarization transfer from 1H nuclei to 23Na nuclei showed that the Na+ cations are well hydrated in the cellulose nanocrystal films. Linewidth analysis in solid-state 23Na NMR showed that the Na+ cations move in confined spaces, and that the Na+ cations in the film having disordered structure are more dynamic than in the films having ordered structure. From lineshape analysis of the 23Na 2D nutation NMR spectra, we can distinguish the Na+ environments within the ordered and disordered films, and find trends in anisotropic interaction parameters between ordered samples with different pitches. These are the first detailed 23Na NMR spectroscopic studies of CNC-Na+ films, and they show that this technique may be a powerful probe for characterizing the extent of order in nanocellulose samples.

Quadrupole relaxation enhancement and polarisation transfer in DMSO solution of [Bi(NO3)3(H2O)3]*18-crown-6 in solid state

ABSTRACT1H spin-lattice relaxation studies have been performed for pure [Bi(NO3)3(H2O)3]*18-crown-6 in powder and its solution in dimethyl sulfoxide (DMSO). The experiments have been carried out in the frequency range of 10 kHz–30 MHz and the temperature range of 240–277 K; at 277 K the solution is already frozen. The 1H relaxation of pure [Bi(NO3)3(H2O)3]*18-crown-6 has been interpreted in terms of three dynamical processes. Quadrupole Relaxation Enhancement effects have been observed in the frozen DMSO solution of [Bi(NO3)3(H2O)3]*18-crown-6. The specific mechanisms of the 1H spin-lattice relaxation enhancement have been discussed distinguishing between effects caused by time independent (residual) and fluctuating 1H-209Bi dipole-dipole interactions.

BEST and SOFAST experiments for resonance assignment of histidine and tyrosine side chains in 13C/15N labeled proteins.

Aromatic amino-acid side chains are essential components for the structure and function of proteins. We present herein a set of NMR experiments for time-efficient resonance assignment of histidine and tyrosine side chains in uniformly 13C/15N-labeled proteins. The use of band-selective 13C pulses allows to deal with linear chains of coupled spins, thus avoiding signal loss that occurs in branched spin systems during coherence transfer. Furthermore, our pulse schemes make use of longitudinal 1H relaxation enhancement, Ernst-angle excitation, and simultaneous detection of 1H and 13C steady-state polarization to achieve significant signal enhancements.

A Semi-Empirical Method for the Estimation of the Hydration Number of Mn(II)-Complexes

A semi-empirical equation to estimate the hydration number of Mn(II) complexes was derived from a database of 49 previously published 1H longitudinal Nuclear Magnetic Relaxation Dispersion profiles. This equation has the longitudinal 1H relaxivity and the molecular weight of the Mn(II) complex under consideration as parameters.

Structural geometry of the layered perovskite-type (CH3CH2CH2NH3)2CuCl4 single crystal near phase transition temperatures

Chemical shifts and spin–lattice relaxation times are measured using 1H MAS NMR, 13C CP/MAS NMR, and 14N MAS NMR techniques to understand the structural geometry and dynamics of the alkyl and ammonium groups in layered perovskite (CH3CH2CH2NH3)2CuCl4. Each proton and carbon may be distinguished using MAS NMR. The 1H MAS NMR chemical shifts as a function of temperature showed a larger variation in the ammonium group than in the alkyl group, while the 1H relaxation time (T1ρ) for the ammonium groups was shorter than that of the alkyl group. The paramagnetic Cu2+ ions in the CH3CH2CH2NH3 cation were bonded with the inorganic layer through the N–H···Cl hydrogen bonds, and were paramagnetic, directly affecting the environment of 1H in NH3. The 13C T1ρ values for CH3 increased with temperature, a trend that has been observed in the alkyl group attached to the CH3CH2CH2NH3 cation because of an increased mobility toward its free end.

Conformational exchange of aromatic side chains by 1H CPMG relaxation dispersion

Aromatic side chains are attractive probes of protein dynamics on the millisecond time scale, because they are often key residues in enzyme active sites and protein binding sites. Further they allow to study specific processes, like histidine tautomerization and ring flips. Till now such processes have been studied by aromatic 13C CPMG relaxation dispersion experiments. Here we investigate the possibility of aromatic 1H CPMG relaxation dispersion experiments as a complementary method. Artifact-free dispersions are possible on uniformly 1H and 13C labeled samples for histidine δ2 and ε1, as well as for tryptophan δ1. The method has been validated by measuring fast folding–unfolding kinetics of the small protein CspB under native conditions. The determined rate constants and populations agree well with previous results from 13C CPMG relaxation dispersion experiments. The CPMG-derived chemical shift differences between the folded and unfolded states are in good agreement with those obtained directly from the spectra. In contrast, the 1H relaxation dispersion profiles in phenylalanine, tyrosine and the six-ring moiety of tryptophan, display anomalous behavior caused by 3J 1H–1H couplings and, if present, strong 13C–13C couplings. Therefore they require site-selective 1H/2H and, in case of strong couplings, 13C/12C labeling. In summary, aromatic 1H CPMG relaxation dispersion experiments work on certain positions (His δ2, His ε1 and Trp δ1) in uniformly labeled samples, while other positions require site-selective isotope labeling.Graphical abstract

Peculiarities of NMR relaxation in micellar gels of Pluronic F-127

Based on the 1H relaxation of transverse nuclear magnetization of triblock-copolymer Pluronic F-127 in D2O, we proposed a model of the associated pluronic structure in which the polyethylene oxide of molecules in neighboring micelles are intertwined in regions of overlapping micellar coronas, while the polypropylene oxide cores of the micelles play a role of nodes in the 3D network.