Conformational Landscape of NADH and Ion Binding in Water/DMSO Mixtures via 31P NMR Spectroscopy.

This study reports on the conformational states of nicotinamide adenine dinucleotide (NADH) in water/DMSO mixtures and examines the influence of ion binding. We observe evidence of conformational changes through a series of NMR techniques, including 31P NMR relaxation (R1 and R2), chemical exchange saturation transfer (CEST), and diffusion-ordered spectroscopy (DOSY) experiments. The observed variation of the conformational states is indicative of the solvent's influence on NADH's structural flexibility. The experimental findings, in combination with viscosity data, are shown to be in line with findings from earlier molecular dynamics studies. The reported observations emphasize the critical role of the solvent environment in determining the conformational states of NADH and similar molecules with relevance for the biophysiological context. The results found herein can help in studying the biophysical behavior of NADH and similar biomolecules and their associated metabolic pathways under various solvent conditions.

Range and sensitivity of 17O nuclear spin-lattice relaxation as a probe of aqueous electrolyte dynamics.

The study of electrolytic solutions is of relevance in many research fields, ranging from biophysics, materials, and colloid science to catalysis and electrochemistry. The dependence of solution dynamics on the nature of electrolytes and their concentrations has been the subject of many experimental and computational studies, yet it remains challenging to obtain a full understanding of the factors that govern solution behavior. Here, we provide additional insights into the behavior of aqueous solutions of alkali chlorides by combining 17O relaxation data with diffusion and viscosity data and contrast their behavior with 1H nuclear magnetic resonance relaxation data. The main findings are that 17O relaxation correlates well with viscosity data but not with diffusion data, while 1H relaxation correlates with neither. Certain ionic trends match known ion-specific series behavior, especially at high concentrations. Notably, we also examine the ranges of the interactions and conclude that the majority of the effects are tied to local water reorientation dynamics.

Spectroscopically dark phosphate features revealed by chemical exchange saturation transfer.

Phosphate is an essential anion in the human body, comprising approximately 1% of the total body weight, and playing a vital role in metabolism, cell membranes, and bone formation. We have recently provided spectroscopic, microscopic, and computational evidence indicating that phosphates can aggregate much more readily in solution than previously thought. This prior work provided indirect evidence through the observation of unusual 31 P NMR relaxation and line-broadening effects with increasing temperature. Here, we show that, under conditions of slow exchange and selective RF saturation, additional features become visible in chemical exchange saturation transfer (CEST) experiments, which appear to be related to the previously reported phosphate clustering. In particular, CEST shows pronounced dips several ppm upfield of the main phosphate resonance at low temperatures, while direct 31 P spectroscopy does not produce any signals in that range. We study the pH dependence of these new spectroscopic features and present exchange and spectroscopic parameters based on fitting the CEST data. These findings could be of importance in the investigation of phosphate dynamics, especially in the biological milieu.

Selective filtration of NMR signals arising from weakly- and strongly-coupled spin systems.

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for analyzing chemical and biological systems. However, in complex solutions with similar molecular components, NMR signals can overlap, making it challenging to distinguish and quantify individual species. In this paper, we introduce new spectral editing sequences that exploit the differences in nuclear spin interactions (J-couplings) between weakly- and strongly-coupled two-spin systems. These sequences selectively attenuate or nullify undesired spin magnetization while they preserve the desired signals, resulting in simplified NMR spectra and potentially facilitating single-species imaging applications. We demonstrate the effectiveness of our approach using a 31P spectral filtration method on a model system of nicotinamide dinucleotide (NAD), which exists in oxidized (NAD+) and reduced (NADH) forms. The presented sequences are robust to field inhomogeneity, do not require additional sub-spectra, and retain a significant portion of the original signal.

Quadrupolar 23Na+ NMR relaxation as a probe of subpicosecond collective dynamics in aqueous electrolyte solutions.

Nuclear magnetic resonance relaxometry represents a powerful tool for extracting dynamic information. Yet, obtaining links to molecular motion is challenging for many ions that relax through the quadrupolar mechanism, which is mediated by electric field gradient fluctuations and lacks a detailed microscopic description. For sodium ions in aqueous electrolytes, we combine ab initio calculations to account for electron cloud effects with classical molecular dynamics to sample long-time fluctuations, and obtain relaxation rates in good agreement with experiments over broad concentration and temperature ranges. We demonstrate that quadrupolar nuclear relaxation is sensitive to subpicosecond dynamics not captured by previous models based on water reorientation or cluster rotation. While ions affect the overall water retardation, experimental trends are mainly explained by dynamics in the first two solvation shells of sodium, which contain mostly water. This work thus paves the way to the quantitative understanding of quadrupolar relaxation in electrolyte and bioelectrolyte systems.

Phosphates form spectroscopically dark state assemblies in common aqueous solutions.

Phosphates and polyphosphates play ubiquitous roles in biology as integral structural components of cell membranes and bone, or as vehicles of energy storage via adenosine triphosphate and phosphocreatine. The solution phase space of phosphate species appears more complex than previously known. We present nuclear magnetic resonance (NMR) and cryogenic transmission electron microscopy (cryo-TEM) experiments that suggest phosphate species including orthophosphates, pyrophosphates, and adenosine phosphates associate into dynamic assemblies in dilute solutions that are spectroscopically "dark." Cryo-TEM provides visual evidence of the formation of spherical assemblies tens of nanometers in size, while NMR indicates that a majority population of phosphates remain as unassociated ions in exchange with spectroscopically invisible assemblies. The formation of these assemblies is reversibly and entropically driven by the partial dehydration of phosphate groups, as verified by diffusion-ordered spectroscopy (DOSY), indicating a thermodynamic state of assembly held together by multivalent interactions between the phosphates. Molecular dynamics simulations further corroborate that orthophosphates readily cluster in aqueous solutions. This study presents the surprising discovery that phosphate-containing molecules, ubiquitously present in the biological milieu, can readily form dynamic assemblies under a wide range of commonly used solution conditions, highlighting a hitherto unreported property of phosphate's native state in biological solutions.

31P spin-lattice and singlet order relaxation mechanisms in pyrophosphate studied by isotopic substitution, field shuttling NMR, and molecular dynamics simulation.

Nuclear spin relaxation mechanisms are often difficult to isolate and identify, especially in molecules with internal flexibility. Here we combine experimental work with computation in order to determine the major mechanisms responsible for 31P spin-lattice and singlet order (SO) relaxation in pyrophosphate, a physiologically relevant molecule. Using field-shuttling relaxation measurements (from 2 µT to 9.4 T) and rates calculated from molecular dynamics (MD) trajectories, we identified chemical shift anisotropy (CSA) and spin-rotation as the major mechanisms, with minor contributions from intra- and intermolecular coupling. The significant spin-rotation interaction is a consequence of the relatively rapid rotation of the -PO32- entities around the bridging P-O bonds, and is treated by a combination of MD simulations and quantum chemistry calculations. Spin-lattice relaxation was predicted well without adjustable parameters, and for SO relaxation one parameter was extracted from the comparison between experiment and computation (a correlation coefficient between the rotational motion of the groups).

Weak nuclear spin singlet relaxation mechanisms revealed by experiment and computation.

Nuclear spin singlet states are often found to allow long-lived storage of nuclear magnetization, which can form the basis of novel applications in spectroscopy, imaging, and in studies of dynamic processes. Precisely how long such polarization remains intact, and which factors affect its lifetime is often difficult to determine and predict. We present a combined experimental/computational study to demonstrate that molecular dynamics simulations and ab initio calculations can be used to fully account for the experimentally observed proton singlet lifetimes in ethyl-d5-propyl-d7-maleate in deuterated chloroform as solvent. The correspondence between experiment and simulations is achieved without adjustable parameters. These studies highlight the importance of considering unusual and difficult-to-control mechanisms, such as dipolar couplings to low-gamma solvent nuclei, and to residual paramagnetic species, which often can represent lifetime limiting factors. These results also point to the power of molecular dynamics simulations to provide insights into little-known NMR relaxation mechanisms.

31P nuclear spin singlet lifetimes in a system with switchable magnetic inequivalence: experiment and simulation.

31P NMR spectroscopy and the study of nuclear spin singlet relaxation phenomena are of interest in particular due to the importance of phosphorus-containing compounds in physiology. We report the generation and measurement of relaxation of 31P singlet order in a chemically equivalent but magnetically inequivalent case. Nuclear magnetic resonance singlet state lifetimes of 31P pairs have heretofore not been reported. Couplings between 1H and 31P nuclei lead to magnetic inequivalence and serve as a mechanism of singlet state population conversion within this molecule. We show that in this molecule singlet relaxation occurs at a rate significantly faster than spin-lattice relaxation, and that anticorrelated chemical shift anisotropy can account for this observation. Calculations of this mechanism, with the help of molecular dynamics simulations and ab initio calculations, provide excellent agreement with the experimental findings. This study could provide guidance for the study of 31P singlets within other compounds, including biomolecules.

7Li intermolecular multiple-quantum coherences in liquids.

We report here evidence for the generation of 7Li multiple-quantum coherences in aqueous solutions outside of regimes where conventional multiple-quantum coherences due to alignment or quadrupolar relaxation could be observed. These coherences are shown to observe nonlinear behavior as a function of concentration, and hence these effects can be identified as arising from intermolecular multiple-quantum coherences. Due to the importance of lithium ion solutions for the study of electrochemical systems, awareness of such coherences is particularly important in the interpretation of experimental results, and new applications using lithium as a probe may become possible on this basis.

Nuclear magnetic resonance spin-lattice relaxation of lithium ions in aqueous solution by NMR and molecular dynamics.

We study the aqueous solvation dynamics of lithium ions using nuclear magnetic resonance spectroscopy, molecular dynamics, and viscosity measurements. Several relaxation mechanisms are examined to explain the strong increases of spin-lattice relaxation toward high concentrations. The use of both 6Li and 7Li isotopes is helpful to identify the quadrupolar contribution to the relaxation rate. In particular, it is found that the quadrupolar interaction constitutes the strongest contribution above a concentration of ∼10 molal. The next-strongest contribution arises from interactions that scale with the square of the gyromagnetic ratio (mostly the dipolar interaction), and the experimental relaxation rates appear to be fully accounted for when these mechanisms are combined over the concentration range up to the saturation concentration. The study of solvation dynamics, particularly at high concentrations, could be of relevance for electrolyte dynamics in aqueous Li-ion rechargeable batteries.

Mapping oscillating magnetic fields around rechargeable batteries.

Power storage devices such as batteries are a crucial part of modern technology. The development and use of batteries has accelerated in the past decades, yet there are only a few techniques that allow gathering vital information from battery cells in a nonivasive fashion. A widely used technique to investigate batteries is electrical impedance spectroscopy (EIS), which provides information on how the impedance of a cell changes as a function of the frequency of applied alternating currents. Building on recent developments of inside-out MRI (ioMRI), a technique is presented here which produces spatially-resolved maps of the oscillating magnetic fields originating from the alternating electrical currents distributed within a cell. The technique works by using an MRI pulse sequence synchronized with a gated alternating current applied to the cell terminals. The approach is benchmarked with a current-carrying wire coil, and demonstrated with commercial and prototype lithium-ion cells. Marked changes in the fields are observed for different cell types.

Nuclear magnetic resonance spectroscopy of rechargeable pouch cell batteries: beating the skin depth by excitation and detection via the casing.

Rechargeable batteries are notoriously difficult to examine nondestructively, and the obscurity of many failure modes provides a strong motivation for developing efficient and detailed diagnostic techniques that can provide information during realistic operating conditions. In-situ NMR spectroscopy has become a powerful technique for the study of electrochemical processes, but has mostly been limited to laboratory cells. One significant challenge to applying this method to commercial cells has been that the radiofrequency, required for NMR excitation and detection, cannot easily penetrate the battery casing due to the skin depth. This complication has limited such studies to special research cell designs or to 'inside-out' measurement approaches. This article demonstrates that it is possible to use the battery cell as a resonator in a tuned circuit, thereby allowing signals to be excited inside the cell, and for them to subsequently be detected via the resonant circuit. Employing this approach, 7Li NMR signals from the electrolyte, as well as from intercalated and plated metallic lithium in a multilayer (rolled) commercial pouch cell battery were obtained. Therefore, it is anticipated that critical nondestructive device characterization can be performed with this technique in realistic and even commercial cell designs.

Sensitive magnetometry reveals inhomogeneities in charge storage and weak transient internal currents in Li-ion cells.

The ever-increasing demand for high-capacity rechargeable batteries highlights the need for sensitive and accurate diagnostic technology for determining the state of a cell, for identifying and localizing defects, and for sensing capacity loss mechanisms. Here, we leverage atomic magnetometry to map the weak induced magnetic fields around Li-ion battery cells in a magnetically shielded environment. The ability to rapidly measure cells nondestructively allows testing even commercial cells in their actual operating conditions, as a function of state of charge. These measurements provide maps of the magnetic susceptibility of the cell, which follow trends characteristic for the battery materials under study upon discharge. In particular, hot spots of charge storage are identified. In addition, the measurements reveal the capability to measure transient internal current effects, at a level of µA, which are shown to be dependent upon the state of charge. These effects highlight noncontact battery characterization opportunities. The diagnostic power of this technique could be used for the assessment of cells in research, quality control, or during operation, and could help uncover details of charge storage and failure processes in cells.

Generalised magnetisation-to-singlet-order transfer in nuclear magnetic resonance.

A variety of pulse sequences have been described for converting nuclear spin magnetisation into long-lived singlet order for nuclear spin-1/2 pairs. Existing sequences operate well in two extreme parameter regimes. The magnetisation-to-singlet (M2S) pulse sequence performs a robust conversion of nuclear spin magnetisation into singlet order in the near-equivalent limit, meaning that the difference in chemical shift frequencies of the two spins is much smaller than the spin-spin coupling. Other pulse sequences operate in the strong-inequivalence regime, where the shift difference is much larger than the spin-spin coupling. However both sets of pulse sequences fail in the intermediate regime, where the chemical shift difference and the spin-spin coupling are roughly equal in magnitude. We describe a generalised version of M2S, called gM2S, which achieves robust singlet order excitation for spin systems ranging from the near-equivalence limit well into the intermediate regime. This closes an important gap left by existing pulse sequences. The efficiency of the gM2S sequence is demonstrated numerically and experimentally for near-equivalent and intermediate-regime cases.

In situ and operando magnetic resonance imaging of electrochemical cells: A perspective.

Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI) of electrochemical devices have become powerful tools for the in situ investigation of electrochemical processes. The techniques often take advantage of NMR's nondestructive/noninvasive properties, its sensitivity to frequency shifts, internal interactions, and transport processes, as well as its ability to measure liquid phases and disordered materials. Here, we provide a perspective on recent work on in situ MRI of electrochemical devices, batteries and relevant model systems, and discuss their applications and promises in assessing device performance, and electrochemical processes in cells.

Diagnosing current distributions in batteries with magnetic resonance imaging.

Batteries and their defects are notoriously difficult to analyze non-destructively, and consequently, many defects and failures remain little noticed and characterized until they cause grave damage. The measurement of the current density distributions inside a battery could reveal information about deviations from ideal cell behavior, and could thus provide early signs of deterioration or failures. Here, we describe methodology for fast nondestructive assessment and visualization of the effects of current distributions inside Li-ion pouch cells. The technique, based on magnetic resonance imaging (MRI), allows measuring magnetic field maps during charging/discharging. Marked changes in the distributions are observed as a function of the state of charge, and also upon sustaining damage. In particular, it is shown that nonlinearities and asymmetries of current distributions could be mapped at different charge states. Furthermore, hotspots of current flow are also shown to correlate with hotspots in charge storage. This technique could potentially be of great utility in diagnosing the health of cells and their behavior under different charging or environmental conditions.

Distortion-free inside-out imaging for rapid diagnostics of rechargeable Li-ion cells.

Safety risks associated with modern high energy-dense rechargeable cells highlight the need for advanced battery screening technologies. A common rechargeable cell exposed to a uniform magnetic field creates a characteristic field perturbation due to the inherent magnetism of electrochemical materials. The perturbation pattern depends on the design, state of charge, accumulated mechanical defects, and manufacturing flaws of the device. The quantification of the induced magnetic field with MRI provides a basis for noninvasive battery diagnostics. MRI distortions and rapid signal decay are the main challenges associated with strongly magnetic components present in most commercial cells. These can be avoided by using Single-Point Ramped Imaging with T1 enhancement (SPRITE). The method is immune to image artifacts arising from strong background gradients and eddy currents. Due to its superior image quality, SPRITE is highly sensitive to defects and the state of charge distribution in commercial Li-ion cells.

Magnetization transfer in liposome and proteoliposome samples that mimic the protein and lipid composition of myelin.

Although magnetization transfer (MT) has been widely used in brain MRI, for example in brain inflammation and multiple sclerosis, the detailed molecular origin of MT effects and the role that proteins play in MT remain unclear. In this work, a proteoliposome model system was used to mimic the myelin environment and to examine the roles of protein, cholesterol, brain cerebrosides, and sphingomyelin embedded in the liposome matrix. Exchange parameters were determined using a double-quantum filter experiment. The goal was to determine the relative contributions to exchange and MT of cerebrosides, sphingomyelin, cholesterol, and proteins in 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayers. The main finding was that cerebrosides produced the strongest exchange effects, and that these were even more pronounced than those found for proteins. Sphingomyelin (which also has exchangeable groups at the head of the fatty acid chains, albeit closer to the lipid acyl chains) and cholesterol showed only minimal transfer. Overall, the extracted exchange rates appeared much smaller than commonly assumed for -OH and -NH groups.

Singlet excitation in the intermediate magnetic equivalence regime and field-dependent study of singlet-triplet leakage.

The examination and optimized preparation of nuclear spin singlet order has enabled the development of new types of applications that rely on potentially long-term polarization storage. Lifetimes several orders of magnitude longer than T1 have been observed. The efficient creation of such states relies on special pulse sequences. The extreme cases of very large and very small magnetic equivalence received primary attention, while relatively little effort has been directed towards studying singlet relaxation in the intermediate regime. The intermediate case is of interest as it is relevant for many spin systems, and would also apply to heteronuclear systems in very low magnetic fields. Experimental evidence for singlet-triplet leakage in the intermediate regime is sparse. Here we describe a pulse sequence for efficiently creating singlets in the intermediate regime in a broad-band fashion. Singlet lifetimes are studied with a specially synthesized molecule over a wide range of magnetic fields using a home-built sample-lift apparatus. The experimental results are supplemented with spin simulations using parameters obtained from ab initio calculations. This work indicates that the chemical shift anisotropy (CSA) mechanism is relatively weak compared to singlet-triplet leakage for the proton system observed over a large magnetic field range. These experiments provide a mechanism for expanding the scope of singlet NMR to a larger class of molecules, and provide new insights into singlet lifetime limiting factors.