NMR Relaxation Parameters Research Articles

Nuclear magnetic resonance as a powerful tool for evaluation of intermolecular interaction: Correlation with rheological measurements of recycled nanocomposite

The degradation of polystyrene nanocomposite was carried out by mechanical recycling after multiple processing of thermo-oxidative ageing. It was found that the degradation of the quaternary salt present in the clay promotes degradation of the polymer. The clay exfoliation was affected by the nanocomposite degradation process as well as the dipolar interactions of polymer chains, which influences the physical and mechanical properties of the final nanocomposite. NMR is a powerful tool for the characterization at the molecular level; it is sensitive to variations in local segmental and global movements. The correlation between NMR relaxation and rheological analyses in polymer nanocomposites was observed. This study aims to understand the complex effects of degradation in polymeric systems containing nanoparticles. Several 1H NMR relaxation parameters were analyzed. From the base line of the domain curves, the dipolar interaction phenomenon in polystyrene chains was investigated. The polymer chain heterogeneity was determined quantitatively from the MSE-FID, using a combination of Abragamian, Gaussian and exponential functions to fit experimental data. At least three domains: rigid, intermediate and mobile phases were identified based on the molecular mobilities.

Low-Temperature NMR Study of the Semiconductor Mineral CuFeS2

Characteristic NMR parameters of 63,65Cu in the local magnetic field of the semiconductor mineral chalcopyrite CuFeS2 were measured in the range 26–77 K. The behavior of the 63,65Cu NMR spectral and relaxation parameters in the local field indicated that a magnetic phase transition related to antiferromagnetic ordering of Cu2+ magnetic moments did not occur at ~50 K in the studied CuFeS2 sample.

13C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis

Excipients used in the solid drug formulations differ in their NMR relaxation and 13C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous α-lactose, α-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon® were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5s to 1200s) and T1ρI parameters (from 2ms to 73ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations.

Flexibility at a glycosidic linkage revealed by molecular dynamics, stochastic modeling, and (13)C NMR spin relaxation: conformational preferences of α-L-Rhap-α-(1 → 2)-α-L-Rhap-OMe in water and dimethyl sulfoxide solutions.

The monosaccharide L-rhamnose is common in bacterial polysaccharides and the disaccharide α-L-Rhap-α-(1 → 2)-α-L-Rhap-OMe represents a structural model for a part of Shigella flexneri O-antigen polysaccharides. Utilization of [1'-(13)C]-site-specific labeling in the anomeric position at the glycosidic linkage between the two sugar residues facilitated the determination of transglycosidic NMR (3)JCH and (3)JCC coupling constants. Based on these spin-spin couplings the major state and the conformational distribution could be determined with respect to the ψ torsion angle, which changed between water and dimethyl sulfoxide (DMSO) as solvents, a finding mirrored by molecular dynamics (MD) simulations with explicit solvent molecules. The (13)C NMR spin relaxation parameters T1, T2, and heteronuclear NOE of the probe were measured for the disaccharide in DMSO-d6 at two magnetic field strengths, with standard deviations ≤1%. The combination of MD simulation and a stochastic description based on the diffusive chain model resulted in excellent agreement between calculated and experimentally observed (13)C relaxation parameters, with an average error of <2%. The coupling between the global reorientation of the molecule and the local motion of the spin probe is deemed essential if reproduction of NMR relaxation parameters should succeed, since decoupling of the two modes of motion results in significantly worse agreement. Calculation of (13)C relaxation parameters based on the correlation functions obtained directly from the MD simulation of the solute molecule in DMSO as solvent showed satisfactory agreement with errors on the order of 10% or less.

High-Rate Electrochemistry in Bulk (um) Particles: NMR Insights into Nb2O5

Recent studies have shown that Nb2O5 can act as a high-rate cathode material in lithium-ion batteries; mesoporous, orthorhombic T-Nb2O5 has demonstrated reversible capacity of 130 mA∙h∙g-1 at a 10C rate and over 100 mA∙h∙g-1 even at a 100C rate.1,2 Intercalation in this material therefore occurs at noticeably higher rates than in a standard lithium-ion battery. Inspired by work3,4 on the relationship between structure and electrochemical performance in Nb2O5polymorphs, an investigation was opened into the mechanisms responsible for the rapid lithium-ion intercalation in niobium(V) oxides. TT (pseudohexagonal), T (orthorhombic), B (monoclinic), and H (monoclinic) polymorphs of Nb2O5 were synthesised by calcining NbO2 for 24 hours over a range of temperatures. In addition to low cost and ease of synthesis, solid state preparative methods were selected in an effort to characterise inherent properties of the bulk crystal structure of the various polymorphs, as it is well known that nanostructuring can fundamentally change the kinetics and thermodynamics of intercalation reactions. Samples were prepared at every 50 °C interval from 200 °C to 1100 °C and analysed by x-ray diffraction (XRD). Electrochemically, the Wadsley–Roth type shear structure of H-Nb2O5 exhibited the highest capacity, reversibly intercalating more than one electron per transition metal ion. Akin to the nanostructured mesoporous oxides, TT-Nb2O5 and T-Nb2O5 from NbO2displayed impressive intercalation kinetics and no phase change upon discharge-charge cycling; this result is somewhat unexpected considering the large (μm) scale of the particles in this investigation. Solid state NMR was employed to examine lithiation mechanisms and energy barriers within the high-rate (T) and high-capacity (H) phases. Results will be presented from ex situ magic angle spinning (MAS) 93Nb, 17O, and 7Li solid state NMR experiments, which were performed on pristine niobia samples and cycled coin cell cathodes to examine the different local atomic environments within each structural moiety and to correlate local and long range structural changes and lithium transport with rate performance for the different polymorphs. Changes in NMR chemical shift, peak shape, intensity, and relaxation parameters were observed as a function of degree of lithiation and in variable temperature experiments. 1. Augustyn, V. et al. Nat. Mater. 12, 518–522 (2013). 2. Brezesinski, K. et al. J. Am. Chem. Soc. 132, 6982–6990 (2010). 3. Kumagai, N. et al. J. Electrochem. Soc. 146, 3203–3210 (1999). 4. Rosario, A. V. & Pereira, E. C. J. Solid State Electrochem. 9, 665–673 (2005). Figure 1

Solution structure, aggregation behavior, and flexibility of human relaxin-2.

Relaxin is a member of the relaxin/insulin peptide hormone superfamily and is characterized by a two-chain structure constrained by three disulfide bonds. Relaxin is a pleiotropic hormone and involved in a number of physiological and pathogenic processes, including collagen and cardiovascular regulation and tissue remodelling during pregnancy and cancer. Crystallographic and ultracentrifugation experiments have revealed that the human form of relaxin, H2 relaxin, self-associates into dimers, but the significance of this is poorly understood. Here, we present the NMR structure of a monomeric, amidated form of H2 relaxin and compare its features and behavior in solution to those of native H2 relaxin. The overall structure of H2 relaxin is retained in the monomeric form. H2 relaxin amide is fully active at the relaxin receptor RXFP1 and thus dimerization is not required for biological activity. Analysis of NMR chemical shifts and relaxation parameters identified internal motion in H2 relaxin at the pico-nanosecond and milli-microsecond time scales, which is commonly seen in other relaxin and insulin peptides and might be related to function.

Exploring the backbone dynamics of native spider silk proteins in Black Widow silk glands with solution-state NMR spectroscopy

Spider dragline silk is an outstanding biopolymer with a strength that exceeds steel by weight and a toughness greater than high-performance fibers like Kevlar. For this reason, understanding how a spider converts the gel-like, aqueous protein spinning dope within the major ampullate (MA) gland into a super fiber is of great importance for developing future biomaterials based on spider silk. In this work, the initial state of the silk proteins within Black Widow MA glands was probed with solution-state NMR spectroscopy. 15N relaxation parameters, T1, T2 and 15N-{1H} steady-state NOE were measured for twelve backbone environments at two spectrometer frequencies, 500 and 800 MHz. The NMR relaxation parameters extracted for all twelve environments are consistent with MA silk protein backbone dynamics on the fast sub-nanosecond timescale. Therefore, it is concluded that the repetitive core of spider MA proteins are in an unfolded, highly flexible state in the MA gland.

NMR Order Parameter Determination from Long Molecular Dynamics Trajectories for Objective Comparison with Experiment.

Functional protein motions covering a wide range of time scales can be studied, among other techniques, by NMR and by molecular dynamics (MD) computer simulations. MD simulations of proteins now routinely extend into the hundreds of nanoseconds time scale range exceeding the overall tumbling correlation times of proteins in solution by several orders of magnitude. This provides a unique opportunity to rigorously validate these simulations by quantitative comparison with model-free order parameters derived from NMR relaxation experiments. However, presently there is no consensus on how such a comparison is best done. We address here how this can be accomplished in a way that is both efficient and objective. For this purpose, we analyze (15)N R1 and R2 and heteronuclear {(1)H}-(15)N NOE NMR relaxation parameters computed from 500 ns MD trajectories of 10 different protein systems using the model-free analysis. The resulting model-free S(2) order parameters are then used as targets for S(2) values computed directly from the trajectories by the iRED method by either averaging over blocks of variable lengths or by using exponentially weighted snapshots (wiRED). We find that the iRED results are capable of reproducing the target S(2) values with high accuracy provided that the averaging window is chosen 5 times the length of the overall tumbling correlation time. These results provide useful guidelines for the derivation of NMR order parameters from MD for a meaningful comparison with their experimental counterparts.

Investigation of Polymer‐Filler Interactions in TiO2‐Filled Poly(n‐alkyl methacrylates) by Low‐Field NMR Relaxometry

Low‐field NMR relaxometry is sensitive to molecular mobility within well‐defined time windows and can thus be applied to study interactions between polymers and inorganic filler particles in composite materials. Volume fraction and dispersion of the filler influence the polymer chain dynamics, which also modify the macroscopic properties of the polymer composites. As model systems, TiO2‐filled poly(n‐alkyl methacrylates) with different side‐chain lengths and filler contents are prepared by melt mixing. Several 1H NMR relaxation parameters, which are sensitive and selective toward polymer–filler interactions, are investigated at a Larmor frequency of 20 MHz as a function of temperature. Both physical and empirical models are used to analyze the NMR data, and the results are compared with the aim of an unambiguous detection of polymer–filler interactions. image

Biopolymers and Biomacromolecules Solvent Dynamics

SummaryBiomacromolecules in solution modify the structure and the dynamics of the bulk water at the solute‐solvent interface. The ordering effects of biomolecules, in particular proteins, are extended for several angstroms. The role of the hydration shells around a protein has yet to be completely understood. Hydrated proteins maintain more dynamic flexibility with respect to the dried system, which is an important property in protein‐protein and/or protein‐ligand recognition processes. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on analysis of the effects of protein‐solvent interactions on water protons NMR relaxation parameters. The water proton spin‐lattice relaxation rate in protein solution is analyzed considering all possible dipolar contributions from coupled protons environments. The analysis of both selective and non‐selective water spin‐lattice relaxation rates allowed the calculation of the average effective correlation time for the water molecules at the protein interface and the evaluation of the long range ordering effect of the protein surface.

Evaluating Poly(lactic acid) Fiber Reinforcement with Modified Tannins

PLA fibers with high tannin content are prepared by melt spinning PLA with tannin acetate (TanAc) prepared from a condensed tannin. PLA with up to 50% TanAc content can be readily processed, giving melt spun fibers suitable for further processing as textile fibers or for carbonization. The PLA molecular weight profile is not impacted by blending with TanAc. Melt processing does not de-esterify the TanAc nor lead to transesterification between tannin and PLA chains in the presence of a tin catalyst. PLA polymer properties and NMR relaxation parameters suggest higher TanAc content gives greater change to PLA molecular mobility and reduced crystallinity, particularly in the presence of the transesterification catalyst.

Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI) in Permanent Focal Cerebral Ischemia in Rat

Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT) parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI), were quantified together with conventional relaxation parameters (T1, T2 and T1ρ) and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1) Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2) RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3) MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4) ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

Water-Protein Interactions: The Secret of Protein Dynamics

Water-protein interactions help to maintain flexible conformation conditions which are required for multifunctional protein recognition processes. The intimate relationship between the protein surface and hydration water can be analyzed by studying experimental water properties measured in protein systems in solution. In particular, proteins in solution modify the structure and the dynamics of the bulk water at the solute-solvent interface. The ordering effects of proteins on hydration water are extended for several angstroms. In this paper we propose a method for analyzing the dynamical properties of the water molecules present in the hydration shells of proteins. The approach is based on the analysis of the effects of protein-solvent interactions on water protons NMR relaxation parameters. NMR relaxation parameters, especially the nonselective (R 1 NS ) and selective (R 1 SE ) spin-lattice relaxation rates of water protons, are useful for investigating the solvent dynamics at the macromolecule-solvent interfaces as well as the perturbation effects caused by the water-macromolecule interactions on the solvent dynamical properties. In this paper we demonstrate that Nuclear Magnetic Resonance Spectroscopy can be used to determine the dynamical contributions of proteins to the water molecules belonging to their hydration shells.

New program for computation of the thermodynamic, spectral, and NMR relaxation parameters of coordination compounds in complex systems

A new approach providing a direct calculations of equilibrium constants, parameters of the chemical exchange reactions, and spectral characteristics of complexes on the basis of data of several methods including pH-potentiometry, multi-wavelength electronic spectroscopy, and NMR relaxation within a single computer program was proposed and realized in the program STALABS. Application of the STALABS program has been demonstrated on the example of investigation of the complex nickel(II) - L-histidine system by joint usage of the above three methods.

Molecular Dynamics of Class A β-lactamases—Effects of Substrate Binding

The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the free and substrate-bound forms of TEM-1 (with benzylpenicillin) and PSE-4 (with carbenicillin) were recorded (totaling 4.0 μs). Substrates were parameterized with the CHARMM General Force Field. In both enzymes, the Ω loop exhibits a marked flexibility increase upon substrate binding, supporting the hypothesis of substrate gating. However, specific interactions that are formed or broken in the Ω loop upon binding differ between the two enzymes: dynamics are conserved, but not specific interactions. Substrate binding also has a global structuring effect on TEM-1, but not on PSE-4. Changes in TEM-1’s normal modes show long-range effects of substrate binding on enzyme dynamics. Hydrogen bonds observed in the active site are mostly preserved upon substrate binding, and new, transient interactions are also formed. Agreement between NMR relaxation parameters and our theoretical results highlights the dynamic duality of class A β-lactamases: enzymes that are highly structured on the ps-ns timescale, with important flexibility on the μs-ms timescale in regions such as the Ω loop.

Mucoadhesive properties of tamarind-seed polysaccharide/hyaluronic acid mixtures: A nuclear magnetic resonance spectroscopy investigation

Mixtures of tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA), which are employed as artificial tears for ophthalmic applications in the eye dry syndrome, were investigated by NMR spectroscopy by analyzing the effect of TSP/HA ratio and total concentration on their capability to form stable aggregates with enhanced mucoadhesive properties over those of the separate polysaccharides. The effect of TSP, HA or TSP/HA mixtures on the affinity of diclofenac sodium salt (DS) to mucin (BSM) was ascertained by means of proton selective relaxation rate measurements and assumed as the basis to compare polysaccharides mucoadhesive properties. The NMR relaxation parameters of pure DS (2mM), binary DS/BSM (5mg/mL or 10mg/mL) and ternary DS/BSM/polysaccharide systems (polysaccharide=TSP, HA or variable ratios TSP/HA mixtures) were compared in aqueous medium. The experimental data demonstrate that the minimum concentration of 1.5mg/mL of each polysaccharide is needed to have formation of a stable TSP/HA aggregate endowed with NMR detectable mucoadhesive properties and inside which reciprocal synergistic interaction occurs.

Studies on Wheat Resistant Starch by NMR Technique

A low field magnetic resonance technique was used to analyze the water mobility character about wheat starch and its resistant starch (RS) suspensions at different water activity. RS was obtained from wheat starch by high temperature and high pressure method. Scanning electron microscopy(SEM), X-ray diffraction analysis and differential scanning calorimetry (DSC) analysis were used to evaluate the variation between the starch and RS after treatment. Compared with the original starch, it was suggested that the capacity of combining water of RS was stronger than starche from the NMR relaxation parameters, but RS’s water holding capacity (WHC) was lower than that of starch. Experiments indicated that water mobility character was lower in RS. This study on the water mobility character of starch and RS was significant for the starch industry, and showed the perspective of NMR and MRI technique potential utilization in the food science field.

Sucrose in aqueous solution revisited, Part 2: Adaptively biased molecular dynamics simulations and computational analysis of NMR relaxation

We report 100 ns molecular dynamics simulations, at various temperatures, of sucrose in water (with concentrations of sucrose ranging from 0.02 to 4M), and in a 7:3 water-DMSO mixture. Convergence of the resulting conformational ensembles was checked using adaptive-biased simulations along the glycosidic Φ and ψ torsion angles. NMR relaxation parameters, including longitudinal (R₁) and transverse (R₂) relaxation rates, nuclear Overhauser enhancements (NOE), and generalized order parameter (S²) were computed from the resulting time-correlation functions. The amplitude and time scales of molecular motions change with temperature and concentration in ways that track closely with experimental results, and are consistent with a model in which sucrose conformational fluctuations are limited (with 80-90% of the conformations having ϕ-ψ values within 20° of an average conformation), but with some important differences in conformation between pure water and DMSO-water mixtures.

Determination of dispersity of aqueous emulsions of hydrocarbons by nuclear magnetic resonance relaxometry

We have used nuclear magnetic resonance relaxometry to study emulsions of viscous crude oils for water concentrations in the range 4.9-50.1 wt.%. We obtained the dependences of the proton relaxation parameters for the components of the emulsions (water in droplets, hydrocarbon medium, and boundary phase) on their treatment parameters and the water concentration. The experimental results are interpreted within a proposed model for the proton dynamics. We establish experimental relations between the NMR relaxation parameters and the integral diameters of the water droplets, characterizing their size distribution, for emulsions of crude oils, residual oils, and bitumens.

Proton magnetic relaxation in a disperse “dry water” nanosystem

We have studied the characteristic features of proton magnetic relaxation in a disperse “dry water” nanosystem. We have determined the effect of the microstructure of the “dry water” on its NMR relaxation parameters.