Proton NMR Relaxation Research Articles

Unified Description of Proton NMR Relaxation in Water, Acetonitrile, and Methane from Molecular Dynamics Simulations in the Liquid, Supercritical, and Gas Phases.

A comprehensive calculation of proton NMR relaxation in water, acetonitrile, and methane across a wide range of the phase diagram is provided via ab initio and force-field-based molecular dynamics simulations. The formalism used for the spin-rotation (SR) contribution to relaxation is developed for use with any molecular symmetry and utilizes the full molecular SR tensors, which are calculated from first-principles via Kohn-Sham (KS) DFT. In combination with calculations of the dipolar contribution, near-quantitative agreement with total measured relaxation rates is achieved.

NMR proton relaxation for measuring the relative concentration of nanoparticles in liquids.

The measurement of relative concentration of nanoparticles in liquids has been investigated using NMR proton relaxation, addressing a gap in analytical capabilities for highly concentrated dispersions. This technique has a limited footprint, short measurement time and ease of operation making it a promising quality control method to support the development and manufacture of nanomaterials.

Earth's field NMR relaxation of pre-polarised water protons for real-time detection of free-radical formation.

Real-time imaging of free-radical formation is important in physical chemistry, biochemistry, and radiobiology, especially for the study of radiation dose-rate effects. Herein, we show for the first time that the formation of free radicals during the time course of a chemical reaction can be imaged through NMR relaxation measurements of water protons in the Earth's magnetic field, in an open-coil spectrometer. The relaxation rate constants of water magnetisation are enhanced as reactions leading to the formation of hydroxyl radicals and oxygen proceed on the timescale of tens of minutes. The reaction rate of iodide-catalysed H2O2 decay was followed by Earth-field 1H NMR relaxation in real time. The relaxivities of the reaction product and several other paramagnetic compounds were determined. Spin-trap molecules were then used to capture ˙OH radical species, thus altering the reaction rate in proportion to the formation of new paramagnetic compounds. Thereby, a new experimental method for magnetic resonance imaging of the formation of intermediate and stable radical species in water is proposed.

Water proton NMR relaxation revisited: Ultrahighly diluted aqueous solutions beyond Avogadro’s limit prepared by iterative centesimal dilution under shaking cannot be considered as pure solvent

• Ultramolecular dilutions prepared according to homeopathic pharmacopoeia differ from solvent and from simply diluted samples. • Evidence for an unexpected gradual increase of correlation times of water with dilution in ultrahighly diluted solutions. • Evidence for solute-induced nanostructures in aqueous high dilutions growing with dilution. • Nanostructures result from nucleation between the solute, nanobubbles and elements coming from the medium during preparation. • Nanostructures in ultrahigh dilutions, even ultramolecular, enhance leaching processes in glass containers. The biological activity of ultrahigh dilutions (HDs) as used in homeopathy, especially those beyond Avogadro's limit, is still controversial and an intriguing problem for scientists. Homeopathic remedies are mostly prepared by iterative centesimal dilution under vigorous shaking, called dynamization. Cn corresponds to a dilution factor of 10 -2n , and C12 (10 -24 ) to the theoretical limit of molecular presence. Since the 1990 s, NMR relaxation of water protons has emerged as a potent tool for investigating HDs. This article reviews studies of high methodological quality by five independent teams over more than two decades. They demonstrate an increase in T1 and T1/T2, with a decrease in T2, although less constant, in dynamized aqueous HDs. No variation was observed in the similarly treated solvent controls. The phenomenon seems to be common, regardless of solute, dissolved oxygen, material used (glass or plastic), method of shaking, frequency from 0.02 to 600 MHz. Strikingly, the changes in relaxation times increased gradually with dilution, even in the C12-C30 ultramolecular range and they totally vanished after a heating–cooling cycle directly applied on the sealed NMR tubes. The results were interpreted in terms of increasing correlation times of water, greater than 10 −8 s, resulting from the formation of growing solute-induced nanostructures involving nanobubbles and various elements coming from the medium, the atmosphere and the container. Another unexpected result was that HDs were able to enhance some leaching processes in glass containers.

Sensitivity of Proton NMR Relaxation and Proton NMR Diffusion Measurements to Olive Oil Adulterations with Vegetable Oils.

Olive oils and, in particular, extra-virgin olive oils (EVOOs) are one of the most frauded food. Among the different adulterations of EVOOs, the mixture of high-quality olive oils with vegetable oils is one of the most common in the market. The need for fast and cheap techniques able to detect extra-virgin olive oil adulterations was the main motivation for the present research work based on 1H NMR relaxation and diffusion measurements. In particular, the 1H NMR relaxation times, T1 and T2, measured at 2 and 100 MHz on about 60 EVOO samples produced in Italy are compared with those measured on four different vegetable oils, produced from macadamia nuts, linseeds, sunflower seeds, and soybeans. Self-diffusion coefficients on this set of olive oils and vegetable oil samples were measured by means of the 1H NMR diffusion ordered spectroscopy (DOSY) technique, showing that, except for the macadamia oil, other vegetable oils are characterized by an average diffusion coefficient sensibly different from extra-virgin olive oils. Preliminary tests based on both NMR relaxation and diffusometry methods indicate that eventual adulterations of EVOO with linseed oil and macadamia oil are the easiest and the most difficult frauds to be detected, respectively.

Rapid monitoring of graphene exfoliation using NMR proton relaxation.

Graphene is now being produced on an industrial scale and there is a pressing need for rapid in-line measurements of particle size for Quality Assurance and Quality Control (QA/QC). Standardised characterisation techniques such as electron microscopy and scanning probe microscopy can be time consuming and may require pre-processing steps and/or solvent elimination prior to measurements. Herein, we demonstrate the use of nuclear magnetic resonance (NMR) proton relaxation as a powerful method for monitoring the sonication assisted liquid phase exfoliation of graphene. This technique requires little or no sample preparation and the resulting spin-spin relaxation time showed a strong correlation with particle size, exfoliation yield and specific surface area measurements. As the NMR proton relaxation method is rapid, inexpensive, and can potentially be operated in-line, it shows great promise to become a valuable QA/QC method for graphene production methods in liquid.

Using nuclear magnetic resonance proton relaxation to probe the surface chemistry of carbon 2D materials.

Nanomaterials exhibit a high surface-area-to-mass ratio, making surface properties key to optimising product performance. However, characterising surfaces at the nanoscale is difficult to achieve, especially as nanomaterials are often in liquid dispersions. Herein, we demonstrate the use of nuclear magnetic resonance proton relaxation for rapid characterisation of the surface chemistry of graphitic materials.

Monitoring of the sedimentation kinetics of vaccine adjuvants using water proton NMR relaxation.

Suspensions of solid particles find applications in many areas-mining, waste treatment, and in pharmaceutical formulations. Pharmaceutical suspensions include aluminum-adjuvanted vaccines are widely administered to millions of people worldwide annually. Hence, the stability parameters of such suspensions, for example, sedimentation rate and the compactness of the formed sediments, are of great interest to achieve the most optimal and stable formulations. Unlike currently used analytical techniques involving visual observations and/or monitoring of several optical properties using specialized glassware, water proton nuclear magnetic resonance (wNMR) used in this work allows one to analyze samples in their original sealed container regardless of its opacity and/or labeling. It was demonstrated that the water proton transverse relaxation rate could be used to monitor in real time the sedimentation process of two widely used aluminum adjuvants-Alhydrogel® and Adju-Phos®. Using wNMR, we obtained valuable information on the sedimentation rate, dynamics of the supernatant and sediment formation, and the sedimentation volume ratio (SVR) reflecting the compactness of the formed sediment. Results on SVR from wNMR were verified by caliper measurements. Verification of the sedimentation rate results from wNMR by other analytical techniques is challenging due to differences in the measured attributes and even units of the reported rate. Nonetheless, our results demonstrate the practical applicability of wNMR as an analytical tool to study pharmaceutical suspensions, for example, aluminum-adjuvanted vaccines, to provide higher quality and more efficient vaccines. Such analyses could be carried out in the original container of a suspension drug product to study its colloidal stability and to monitor its quality over time without compromising product integrity.

NMR relaxation and self-diffusion in aqueous micellar gels of pluronic F-127

Abstract We studied the transverse NMR relaxation of protons of different chemical groups and diffusion of molecules in an aqueous pluronic F-127 system. The system was studied at concentrations of 15, 21 and 28 wt% and in the temperature range of 293–333 K. The dynamic peculiarities in different phases were analyzed based on the NMR relaxation and diffusion data. Our study demonstrated a correlation between phase states, T2 relaxation times of “solid-like” and “liquid” protons of selected chemical groups of polypropylene oxide (PPO) and polyethylene oxide (PEO) blocks, and diffusion coefficients. Transverse NMR relaxation established that the presence of a “solid-like” component of CH3 protons of PEO blocks is observed only at temperatures and concentrations corresponding to the rigid-gel phase, due to entanglements between micellar coronas. At all temperatures and concentrations, some CH3 protons of PPO blocks and some CH2 protons of PEO blocks show “liquid-like” transverse NMR relaxation. Under the conditions corresponding to formation of the rigid-gel phase of the pluronic, relaxation of the “liquid-like” protons additionally accelerates due to entanglements of micellar coronas. Transition of the system to the rigid-gel phase is accompanied by decrease of diffusion coefficients by a factor of 10–104 relative to the diffusivity of free-moving pluronic micelles in the sol phase. Diffusion measurements show that there are pre-transition phenomena, which are characteristic for temperatures and concentrations near sol-gel phase boundaries.

Correlation of Physicochemical Properties of Bach Ho Oils with Proton NMR Relaxation Parameters and Their Temperature Dependence

The physicochemical properties of crude oils (density, viscosity, asphaltene concentrations) from the Bach Ho oilfield (Vietnam) have been correlated with 1H NMR relaxation parameters (spin–lattice and spin–spin relaxation times T1i and T2i, respectively), and their temperature dependence has been studied. The results are discussed in terms of the concept of the formation of structural units (SU) in oils. The standard “alkane line”—the conventional correlation ηТ1,2 = const/Т for viscous oils—has been refined. The temperature dependences of T1,2i have been obtained, which manifest ordering processes in the test oils.

Enhanced NMR relaxation of fluids confined to porous media: A proposed theory and experimental tests.

We propose a theory to account for the NMR relaxation of water protons in situations in which the fluid is confined to porous structures exhibiting a scarce distribution of paramagnetic centers on their surface. Though much of what is stated and assumed concerns the response of water, the model has sufficiently general features to be able to explain proton relaxation of other polar fluids under similar conditions. One of the main results of the paper is to show that the local anisotropy introduced by the dominant dipolar coupling in the relaxation rates of active surface elements induces a measurable dependence on sample orientation in the overall relaxation rates of the saturating fluid provided its confining structure is not statistically isotropic. Measurements of T_{1} proton relaxation on water saturating microcapillary tubes are performed to reveal the effect.

Proton NMR relaxation from molecular dynamics: intramolecular and intermolecular contributions in water and acetonitrile.

NMR relaxation rates for protons in liquid water and neat acetonitrile were computed based on ab initio molecular dynamics (aiMD) with forces from Kohn-Sham (KS) theory as well as force-field (FF) based classical dynamics. Intra- and intermolecular dipole-dipole contributions were separated, and nearly quantitative agreement with experiment was obtained for water. Spin-rotation (SR) contributions to the intramolecular relaxation rate in acetonitrile were computed using nuclear SR coupling tensors obtained from KS theory. Their inclusion improved the total computed intramolecular rate to within a factor of two of experiment. Insufficient sampling of rare short-time collision events between neighboring acetonitrile molecules in the simulations is hypothesized as a major source of error in the intermolecular contributions.

The use of fast field cycling to evaluate the time domain relaxation of starches from tropical fruit seeds

ABSTRACTA proton NMR relaxation study of the molecular dynamics in flour samples of ‘Eugenia uniflora’ (‘Pitanga’), ’Citrus reticulate’ (‘Tangerine’), ‘Prunus persica’ (‘Peach’), ‘Vitis vinifera’ (‘Grape’), and ‘Cucumis melo’ (‘Honeydew melon’) seeds is presented. The spin–lattice relaxation time was obtained over a broad frequency range from 100 kHz to 100 MHz using both conventional and fast field-cycling NMR techniques. This relaxometry study made possible a comparison between the molecular dynamics behaviour of starch from different fruit seeds and from potatoes. I was possible to conclude that the spin–lattice dispersion presents slightly differences for all samples, in particular at low frequencies. All relaxation dispersions could be well interpreted in terms of power-law relaxation models and domains with different power-law relaxation exponents. For the Peach seeds flour the relaxation dispersion at low frequencies was very similar to that observed for potato’s starch incorporated with 5% organoclay Viscogel B8 nanoparticles.

Impact of Exposure Conditions on the Morphology of Polyethylene by Compact NMR

Today many polyethylene (PE) products are employed in long‐term applications that require the use of elevated temperatures and/or contact with different solvents. Both the exposure to heat and solvents can result in morphological changes, compromising the mechanical stability of the material. Disentangling morphological changes induced by either type of exposure and understanding their combined effect is crucial for establishing reliable structure‐property relationships. This, in turn, requires sensitive analytical methods that can probe the complex morphology of PE both in the laboratory and on site. Among existing analytical methods, NMR with compact devices have recently become a key analytical tool for the detailed morphological characterization of a variety of solid polymers including PE. This current work reviews the potential of compact NMR for monitoring and quantifying morphological changes in PE exposed to the aforementioned external conditions. To prove the reliability of compact proton NMR relaxation measurements, the results are compared with data from conventional high‐field proton wide‐line NMR spectroscopy, DSC, and FTIR spectroscopy. It could be shown that simple, static proton relaxation measurements garner detailed information about the exposure‐induced morphological changes through the quantification of phase composition and chain dynamics. Moreover, the NMR method has a key advantage over other methods, because the chain mobility of the soft amorphous phase is a very sensitive microscopic parameter under exposure conditions. The various presented examples and the good agreement of the NMR results with those of other analytical methods show that low‐field NMR is a promising option for in‐situ aging studies.

Pore-size resolved water vapor adsorption kinetics of white cement mortars as viewed from proton NMR relaxation

The dynamic pore structure of partially saturated cement-based material is rather essential to quantify its mass transport and many other properties. To clarify the influence of water removal and re-entry, the low-field nuclear magnetic resonance technique is employed to characterize the pore structure of two white cement mortars during isopropanol exchange and water vapor adsorption kinetics. It is found that, after isopropanol replacement the pore structures of mortars become remarkably coarsen due to the significant collapse of C-S-H interlayer pores, which are only partly reversible at water re-saturation. Consistently, water vapor adsorption is not a simple progressively filling process from finer to coarser pores, but accompanied by continuous expansion of C-S-H gel adsorbing water in priority. Furthermore, the irrecoverable contraction of C-S-H gel is the physical root of irreversible shrinkage. The smaller BET surface area using nitrogen than water is also attributed to the collapse of interlayer pores after drying.

Modulation of hydration characteristics of carbohydrates in aqueous medium of γ-amino butyric acid via volumetric, rheological and time-domain longitudinal NMR relaxation studies

Carbohydrates such as saccharides and their derivatives are engaged in various biological processes such as in transportation and transmission of genetic material, enzymatic processes, and regulation of metabolism. γ-Amino butyric acid (γ-ABA) is a non-protein amino acid and acts as an inhibitory neurotransmitter in the mammalian cerebral cortex. Volumetric, rheological and spectroscopic investigations are helpful to elucidate the molecular interactions occurring between carbohydrates and γ-ABA in aqueous solution. Therefore, the standard state partial molar volumes, V2° and Jones-Dole viscosity B-coefficients of monosaccharides and their derivatives, polyols and disaccharides were determined in molality, mB range (0.05–0.50) mol·kg−1 aqueous solutions of γ-ABA from the precise density and viscosity measurements at temperature range T=(288.15–318.15) K. These data were used to obtain the corresponding volumes of transfer, ΔtrV2° and change in viscosity B-coefficient, ΔB for carbohydrates from water to aqueous solutions of γ-ABA. The taste quality of studied solutes (carbohydrates) has been appraised in the presence of γ-ABA from apparent massic volumes. The volumetric and viscometric interaction coefficients were calculated from the McMillan-Mayer theory of solutions. The expansion coefficients (∂V2°/∂T)P, second-order derivatives (∂2V2°/∂T2)P and dB/dT coefficients were also determined to study the influence of temperature. These quantities have been explained in terms of various interactions occurring in the ternary system on the basis of co-sphere overlap model suggested by Gurney (1953). Proton (1H) NMR relaxation rates (R1) were also obtained for carbohydrates in different γ-ABA solutions made in 9:1 (w/w) (H2O+D2O) solvent, at T=300K. The results have been compared with our previously reported (Banipal et al., 2015, 2016) studies carried out in L-glycine. The stereochemical effects of studied solutes on hydration controlled by their domineering conformations have also been discussed.

Proton NMR relaxometry as probe of gelatinization, plasticization and montmorillonite-loading effects on starch-based materials

The effects of granule disruption, the addition of glycerol and montmorillonite on the granule structure of corn starch were investigated by proton NMR relaxation, through the T2*, T1 and T1ρ relaxation times. Films containing 0%, 1%, 5% and 7%(w/w) of clay were prepared by solution casting and the relaxometry data were compared with those gleaned from WAXD, TGA and SEM techniques. Starch gelatinization without glycerol or clay results in an amorphous and rigid film having a dipole coupling higher than that observed for the granule. The plasticization reduces the chains rigid fraction by more than 20% and increases the adsorption of moisture in the region of greater molecular mobility. The addition of 1% of clay reduces the adsorption of moisture and, in concentrations of 5% and 7%, the agglomerates reduce the plasticization effect. These features studied were observed by the Tube-Reptation and Renormalized Rouse models applied at low frequencies.

Nuclear Magnetic Resonance characterization of traditional homeopathically manufactured copper (Cuprum metallicum) and plant (Gelsemium sempervirens) medicines and controls

NMR proton relaxation is sensitive to the dynamics of the water molecule H2O, through the interaction of the spin of the proton (1H) with external magnetic and electromagnetic fields. We measured dilution and potentization processes through measurements of 1H spin-lattice T1 and spin-spin T2 relaxation times. In order to interpret the recorded fluctuations in T1- or T2-values, experimental data were linearized by investigating how the area under a fluctuating time=f(dilution) curve (dilution integral or DI) changes with dilution. Two kinds of fitting procedures were considered: chi-square fitting with a goodness-of-fit probability, and least absolute deviations criterion with Pearson's linear correlation coefficient. We showed that fluctuations are not attributable to random noise and/or experimental errors, evidencing a memory effect quantifiable by the slope of the DI=f(dilution) straight line. For all experiments, correlation coefficients were found to lie above 0.9999, against 0.999 for random noise. The discrimination between experimental slopes and slopes associated with random noise data was very good at a five-sigma level of confidence (i.e. probability 3×10-7). Discrimination between experimental slopes at a five-sigma level was possible in most cases, with three exceptions: gelsemium aqua pura v gelsemium dilution (four-sigma); copper aqua pura v gelsemium aqua pura (four-sigma) and copper simple dilution v gelsemium simple dilution (three-sigma). All potentized samples show very good discrimination (at least nine-sigma level) against aqua pura, lactose or simple dilution. It was possible to transform the associated relaxation times into a molecular rotational correlation time τc and an average spin-spin distance d. Our experiments thus point to a considerable slowing down of molecular movements (τc>1300ps or T=224-225K) around water molecules up to a distance of 3.7Å, values. It was also possible to rule out other possible mechanisms of relaxation (diffusive motion, 17O-1H relaxation or coupling with the electronic spin, S=1, of dissolved dioxygen molecules). There is clear evidence that homeopathic solutions cannot be considered as pure water as commonly assumed. Instead, we have evidenced a clear memory effect upon dilution/potentization of a substance (water, lactose, copper, gelsemium) reflected by different rotational correlation times and average H⋯H distances. A possible explanation for such a memory effect may lie in the formation of mesoscopic water structures around nanoparticles and/or nanobubbles mediated by zero-point fluctuations of the vacuum electromagnetic field as suggested by quantum field theories. The existence of an Avogadro's 'wall' for homeopathically-prepared medicines is not supported by our data. Rather it appears that all dilutions have a specific material configuration determined by the potentized substance, also by the chemical nature of the containers, and dissolved gases and the electromagnetic environment. This sensitivity of homeopathically-prepared medicines to electromagnetic fields may be amplified by the highly non-linear processing routinely applied in the preparation of homeopathic medicines. Future work is needed in such directions. The time is now ripe for a demystification of the preparation of homeopathic remedies.

Defining the Structural Basis for Allosteric Product Release from E. coli Dihydrofolate Reductase Using NMR Relaxation Dispersion.

The rate-determining step in the catalytic cycle of E. coli dihydrofolate reductase is tetrahydrofolate (THF) product release, which can occur via an allosteric or an intrinsic pathway. The allosteric pathway, which becomes accessible when the reduced cofactor NADPH is bound, involves transient sampling of a higher energy conformational state, greatly increasing the product dissociation rate as compared to the intrinsic pathway that obtains when NADPH is absent. Although the kinetics of this process are known, the enzyme structure and the THF product conformation in the transiently formed excited state remain elusive. Here, we use side-chain proton NMR relaxation dispersion measurements, X-ray crystallography, and structure-based chemical shift predictions to explore the structural basis of allosteric product release. In the excited state of the E:THF:NADPH product release complex, the reduced nicotinamide ring of the cofactor transiently enters the active site where it displaces the pterin ring of the THF product. The p-aminobenzoyl-l-glutamate tail of THF remains weakly bound in a widened binding cleft. Thus, through transient entry of the nicotinamide ring into the active site, the NADPH cofactor remodels the enzyme structure and the conformation of the THF to form a weakly populated excited state that is poised for rapid product release.

Unusual Interfacial Freezing Phenomena in Hexacontane/Silica Composites.

The crystallization behaviors of n-hexacontane (C60H122)/Stöber silica (SiO2) composites with various compositions were investigated by a combination of differential scanning calorimetry (DSC), solid-state 13C nuclear magnetic resonance (solid-state 13C NMR), and proton NMR relaxation experiments. By means of DSC, C60H122 molecules in C60H122/silica composites were observed to be involved in the interfacial freezing not present in the free bulk C60H122. The orientation of C60H122 molecules, being preferentially normal to silica surface, was confirmed by grazing incidence X-ray diffraction experiments on thin n-hexacontane film adsorbed on the silicon wafer with a native SiO2 layer. Inferred from the solid 13C NMR data, the interfacial monolayer is in orthorhombic phase with certain chain disorders. It is speculated that the "interfacial freezing" of C60H122 formed in the presence of silica particles is driven by the combination of the strong attraction between the molecules and the enhanced number of interfacial molecules on the silica surface.