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Purpose: To develop a SNR enhancement method for CEST imaging using a denoising convolutional autoencoder (DCAE) and compare its performance with state‐of‐the‐art denoising methods. Method: The DCAE‐CEST model encompasses an encoder and a decoder network. The encoder learns features from the input CEST Z‐spectrum via a series of one‐dimensional convolutions, nonlinearity applications, and pooling. Subsequently, the decoder reconstructs an output denoised Z‐spectrum using a series of up‐sampling and convolution layers. The DCAE‐CEST model underwent multistage training in an environment constrained by Kullback–Leibler divergence, while ensuring data adaptability through context learning using Principal Component Analysis–processed Z‐spectrum as a reference. The model was trained using simulated Z‐spectra, and its performance was evaluated using both simulated data and in vivo data from an animal tumor model. Maps of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects were quantified using the multiple‐pool Lorentzian fit, along with an apparent exchange‐dependent relaxation metric. Results: In digital phantom experiments, the DCAE‐CEST method exhibited superior performance, surpassing existing denoising techniques, as indicated by the peak SNR and Structural Similarity Index. Additionally, in vivo data further confirm the effectiveness of the DCAE‐CEST in denoising the APT and NOE maps when compared with other methods. Although no significant difference was observed in APT between tumors and normal tissues, there was a significant difference in NOE, consistent with previous findings. Conclusion: The DCAE‐CEST can learn the most important features of the CEST Z‐spectrum and provide the most effective denoising solution compared with other methods. [ABSTRACT FROM AUTHOR]

[Display omitted] Two-dimensional NOE (nuclear Overhauser effect) NMR spectroscopy was employed to investigate the dynamic properties of water within lyotropic bicontinuous lipidic cubic phases (LCPs) formed by monoolein (MO). Experiments observed categorically different effective residence times of water molecules: (i) in proximity to the glycerol moiety of MO, and (ii) adjacent to the hydrophobic chain towards the hydrocarbon tail of MO, as evidenced by the opposite signs of intermolecular NOE cross peaks between protons of water and those of MO in 2D 1H–1H NOESY spectra. Spectroscopic data delineating the different effective residence times of water molecules within both the gyroid (Q II G) and diamond (Q II D) phase groups corresponding to hydration levels of 35 and 40 wt%, respectively, are presented. Additionally, an increase in effective residence time of water molecules in proximity to the glycerol moiety of MO in LCPs was observed upon storage at ambient temperature and in the presence of an additive lipid, cholesterol. Atom-specific NOE build-up curves for protons of water and those of MO are also given. The results presented herein provide new insight into the physicochemical properties and behaviour of water in LCPs, and demonstrate an additional avenue for experimental study of water–lipid interactions and hydration dynamics in model membranes and nanomaterials using 2D NOE NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Purpose: CEST MRI is influenced by fat signal, which can reduce the apparent CEST contrast or lead to pseudo‐CEST effects. Our goal was to develop a fat artifact correction based on multi‐echo fat–water separation that functions stably for 7 T knee MRI data. Methods: Our proposed algorithm utilizes the full complex data and a phase demodulation with an off‐resonance map estimation based on the Z‐spectra prior to fat–water separation to achieve stable fat artifact correction. Our method was validated and compared to multi‐echo–based methods originally proposed for 3 T by Bloch–McConnell simulations and phantom measurements. Moreover, the method was applied to in vivo 7 T knee MRI examinations and compared to Gaussian fat saturation and a published single‐echo Z‐spectrum–based fat artifact correction method. Results: Phase demodulation prior to fat–water separation reduced the occurrence of fat–water swaps. Utilizing the complex signal data led to more stable correction results than working with magnitude data, as was proposed for 3 T. Our approach reduced pseudo‐nuclear Overhauser effects compared to the other correction methods. Thus, the mean asymmetry contrast at 3.5 ppm in cartilage over five volunteers increased from −9.2% (uncorrected) and −10.6% (Z‐spectrum–based) to −1.5%. Results showed higher spatial stability than with the fat saturation pulse. Conclusion: Our work demonstrates the feasibility of multi‐echo–based fat–water separation with an adaptive fat model for fat artifact correction for CEST MRI at 7 T. Our approach provided better fat artifact correction throughout the entire spectrum and image than the fat saturation pulse or Z‐spectrum–based correction method for both phantom and knee imaging results. [ABSTRACT FROM AUTHOR]

Magnetic resonance (MR) is a powerful technique for noninvasively probing molecular species in vivo but suffers from low signal sensitivity. Saturation transfer (ST) MRI approaches, including chemical exchange saturation transfer (CEST) and conventional magnetization transfer contrast (MTC), allow imaging of low‐concentration molecular components with enhanced sensitivity using indirect detection via the abundant water proton pool. Several recent studies have shown the utility of chemical exchange relayed nuclear Overhauser effect (rNOE) contrast originating from nonexchangeable carbon‐bound protons in mobile macromolecules in solution. In this review, we describe the mechanisms leading to the occurrence of rNOE‐based signals in the water saturation spectrum (Z‐spectrum), including those from mobile and immobile molecular sources and from molecular binding. While it is becoming clear that MTC is mainly an rNOE‐based signal, we continue to use the classical MTC nomenclature to separate it from the rNOE signals of mobile macromolecules, which we will refer to as rNOEs. Some emerging applications of the use of rNOEs for probing macromolecular solution components such as proteins and carbohydrates in vivo or studying the binding of small substrates are discussed. [ABSTRACT FROM AUTHOR]

Purpose: The nuclear Overhauser effect (NOE) quantification from the steady‐state NOE imaging suffers from multiple confounding non‐NOE‐specific sources, including direct saturation, magnetization transfer, and relevant chemical exchange species, and is affected by B0 and B1+ inhomogeneities. The B0‐dependent and B1+‐dependent data needed for deconvolving these confounding effects would increase the scan time substantially, leading to other issues such as patient tolerability. Here, we demonstrate the feasibility of brain lipid mapping using an easily implementable transient NOE (tNOE) approach. Methods: This 7T study used a frequency‐selective inversion pulse at a range of frequency offsets between 1.0 and 5.0 parts per million (ppm) and −5.0 and −1.0 ppm relative to bulk water peak. This was followed by a fixed/variable mixing time and then a single‐shot 2D turbo FLASH readout. The feasibility of tNOE measurements is demonstrated on bovine serum albumin phantoms and healthy human brains. Results: The tNOE measurements from bovine serum albumin phantoms were found to be independent of physiological pH variations. Both bovine serum albumin phantoms and human brains showed broad tNOE contributions centered at approximately −3.5 ppm relative to water peak, with presumably aliphatic moieties in lipids and proteins being the dominant contributors. Less prominent tNOE contributions of approximately +2.5 ppm relative to water, presumably from aromatic moieties, were also detected. These aromatic signals were free from any CEST signals. Conclusion: In this study, we have demonstrated the feasibility of tNOE in human brain at 7 T. This method is more scan‐time efficient than steady‐state NOE and provides NOE measurement with minimal confounders. [ABSTRACT FROM AUTHOR]

The nuclear Overhauser effect (NOE) is one of NMR spectroscopy's most important and versatile parameters. NOE is routinely utilized to determine the structures of medium-to-large size biomolecules and characterize protein–protein, protein–RNA, protein–DNA, and protein–ligand interactions in aqueous solutions. Typical [1H,1H] NOESY pulse sequences incorporate water suppression schemes to reduce the water signal that dominates 1H-detected spectra and minimize NOE intensity losses due to unwanted polarization exchange between water and labile protons. However, at high- and ultra-high magnetic fields, the excitation of the water signal during the execution of the NOESY pulse sequences may cause significant attenuation of NOE cross-peak intensities. Using an evolutionary algorithm coupled with artificial intelligence, we recently designed high-fidelity pulses [Water irrAdiation DEvoid (WADE) pulses] that elude water excitation and irradiate broader bandwidths relative to commonly used pulses. Here, we demonstrate that WADE pulses, implemented into the 2D [1H,1H] NOESY experiments, increase the intensity of the NOE cross-peaks for labile and, to a lesser extent, non-exchangeable protons. We applied the new 2D [1H,1H] WADE-NOESY pulse sequence to two well-folded, medium-size proteins, i.e., the K48C mutant of ubiquitin and the Raf kinase inhibitor protein. We observed a net increase of the NOE intensities varying from 30 to 170% compared to the commonly used NOESY experiments. The new WADE pulses can be easily engineered into 2D and 3D homo- and hetero-nuclear NOESY pulse sequences to boost their sensitivity. [ABSTRACT FROM AUTHOR]

• Exact nuclear Overhauser enhancement (eNOE) analysis results in tight distance restraints. • Novel pulse sequences and non-uniform sampling. • Adaption of the eNOE to solid-state NMR. • Advances in eNOE data analysis and structural ensemble calculation. • Biological applications to protein, RNA and DNA structure elucidation. The introduction of the exact nuclear Overhauser enhancement (eNOE) methodology to solution-state nuclear magnetic resonance (NMR) spectroscopy results in tighter distance restraints from NOEs than in convention analysis. These improved restraints allow for higher resolution in structure calculation and even the disentanglement of different conformations of macromolecules. While initial work primarily focused on technical development of the eNOE, structural studies aimed at the elucidation of spatial sampling in proteins and nucleic acids were published in parallel prior to 2018. The period of 2018–2022 saw a continued series of technical innovation, but also major applications addressing biological questions. Here, we review both aspects, covering topics from the implementation of non-uniform sampling of NOESY buildups, novel pulse sequences, adaption of the eNOE to solid-state NMR, advances in eNOE data analysis, and innovations in structural ensemble calculation, to applications to protein, RNA, and DNA structure elucidation. [ABSTRACT FROM AUTHOR]

Purpose: In chemical exchange saturation transfer imaging, saturation effects between −2 to −5 ppm (nuclear Overhauser effects, NOEs) have been shown to exhibit contrast in preclinical stroke models. Our previous work on NOEs in human stroke used an analysis model that combined NOEs and semisolid MT; however their combination might feasibly have reduced sensitivity to changes in NOEs. The aim of this study was to explore the information a 4‐pool Bloch–McConnell model provides about the NOE contribution in ischemic stroke, contrasting that with an intentionally approximate 3‐pool model. Methods: MRI data from 12 patients presenting with ischemic stroke were retrospectively analyzed, as well as from six animals induced with an ischemic lesion. Two Bloch–McConnell models (4 pools, and a 3‐pool approximation) were compared for their ability to distinguish pathological tissue in acute stroke. The association of NOEs with pH was also explored, using pH phantoms that mimic the intracellular environment of naïve mouse brain. Results: The 4‐pool measure of NOEs exhibited a different association with tissue outcome compared to 3‐pool approximation in the ischemic core and in tissue that underwent delayed infarction. In the ischemic core, the 4‐pool measure was elevated in patient white matter (1.20±0.20) and in animals (1.27±0.20). In the naïve brain pH phantoms, significant positive correlation between the NOE and pH was observed. Conclusion: Associations of NOEs with tissue pathology were found using the 4‐pool metric that were not observed using the 3‐pool approximation. The 4‐pool model more adequately captured in vivo changes in NOEs and revealed trends depending on tissue pathology in stroke. [ABSTRACT FROM AUTHOR]

Purpose: A non‐invasive magnetization transfer indirect spin labeling (MISL) MRI method is developed to quantify the water exchange between cerebrospinal fluid (CSF) and other tissues in the brain and to examine the age‐dependence of water exchange. Method: In the pulsed MISL, we implemented a short selective pulse followed by a post‐labeling delay before an MRI acquisition with a long echo time; in the continuous MISL, a train of saturation pulses was applied. MISL signal (∆Z) was obtained by the subtraction of the label MRI at −3.5 ppm from the control MRI at 200 ppm. CSF was extracted from the mouse ventricles for the MISL optimization and validation. Comparison between wild type (WT) and aquaporin‐4 knockout (AQP4−/−) mice was performed to examine the contributions of CSF water exchange, whereas its age‐dependence was investigated by comparing the adult and young WT mice. Results: The pulsed MISL method observed that the MISL signal reached the maximum at 1.5 s. The continuous MISL method showed the highest MISL signal in the fourth ventricle (∆Z = 13.5% ± 1.4%), whereas the third ventricle and the lateral ventricles had similar MISL ∆Z values (∆Z = 12.0% ± 1.8%). Additionally, significantly lower ∆Z (9.3%–18.7% reduction) was found in all ventricles for the adult mice than those of the young mice (p < 0.02). For the AQP4−/− mice, the ∆Z values were 5.9%–8.3% smaller than those of the age‐matched WT mice in the lateral and fourth ventricles, but were not significant. Conclusion: The MISL method has a great potential to study CSF water exchange with the surrounding tissues in brain. [ABSTRACT FROM AUTHOR]

Purpose: To develop a SNR enhancement method for chemical exchange saturation transfer (CEST) imaging using a denoising convolutional autoencoder (DCAE), and compare its performance with state-of-the-art denoising methods., Method: The DCAE-CEST model encompasses an encoder and a decoder network. The encoder learns features from the input CEST Z-spectrum via a series of 1D convolutions, nonlinearity applications and pooling. Subsequently, the decoder reconstructs an output denoised Z-spectrum using a series of up-sampling and convolution layers. The DCAE-CEST model underwent multistage training in an environment constrained by Kullback-Leibler divergence, while ensuring data adaptability through context learning using Principal Component Analysis processed Z-spectrum as a reference. The model was trained using simulated Z-spectra, and its performance was evaluated using both simulated data and in-vivo data from an animal tumor model. Maps of amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) effects were quantified using the multiple-pool Lorentzian fit, along with an apparent exchange-dependent relaxation metric., Results: In digital phantom experiments, the DCAE-CEST method exhibited superior performance, surpassing existing denoising techniques, as indicated by the peak SNR and Structural Similarity Index. Additionally, in vivo data further confirms the effectiveness of the DCAE-CEST in denoising the APT and NOE maps when compared to other methods. While no significant difference was observed in APT between tumors and normal tissues, there was a significant difference in NOE, consistent with previous findings., Conclusion: The DCAE-CEST can learn the most important features of the CEST Z-spectrum and provide the most effective denoising solution compared to other methods.

31P MR spectroscopic imaging (MRSI) is a versatile technique to study phospholipid precursors and energy metabolism in the healthy and diseased human brain. However, mainly due to its low sensitivity, 31P MRSI is currently limited to research purposes. To obtain 3D 31P MRSI spectra with improved signal‐to‐noise ratio on clinical 3 T MR systems, we used a coil combination consisting of a dual‐tuned birdcage transmit coil and a 31P eight‐channel phased‐array receive insert. To further increase resolution and sensitivity we applied WALTZ4 1H decoupling and continuous wave nuclear Overhauser effect (NOE) enhancement and acquired high‐quality MRSI spectra with nominal voxel volumes of ~ 17.6 cm3 (effective voxel volume ~ 51 cm3) in a clinically relevant measurement time of ~ 13 minutes, without exceeding SAR limits. Steady‐state NOE enhancements ranged from 15 ± 9% (γ‐ATP) and 33 ± 3% (phosphocreatine) to 48 ± 11% (phosphoethanolamine). Because of these improvements, we resolved and detected all 31P signals of metabolites that have also been reported for ultrahigh field strengths, including resonances for NAD+, NADH and extracellular inorganic phosphate. T1 times of extracellular inorganic phosphate were longer than for intracellular inorganic phosphate (3.8 ± 1.4s vs 1.8 ± 0.65 seconds). A comparison of measured T1 relaxation times and NOE enhancements at 3 T with published values between 1.5 and 9.4 T indicates that T1 relaxation of 31P metabolite spins in the human brain is dominated by dipolar relaxation for this field strength range. Even although intrinsic sensitivity is higher at ultrahigh fields, we demonstrate that at a clinical field strength of 3 T, similar 31P MRSI information content can be obtained using a sophisticated coil design combined with 1H decoupling and NOE enhancement. [ABSTRACT FROM AUTHOR]

2D NMR is an immensely powerful structural tool but it is time‐consuming. Targeting individual chemical groups by selective excitation in a 1D experiment can give the information required far more quickly. A major problem, however, is that proton NMR spectra are often extensively overlapped, so that in practice only a minority of sites can be selectively excited. Here we overcome that problem using a fast, single‐scan method that allows selective excitation of the signals of a single proton multiplet even where it is severely overlapped by other multiplets. The advantages of the method are illustrated in a selective 1D NOESY experiment, the most efficient way to determine relative configuration unambiguously by NMR. The new approach presented here has the potential to broaden significantly the applicability of selective excitation and unlock its real potential for many other experiments. [ABSTRACT FROM AUTHOR]

With good contrast in T 1 and T 2 weighted imaging as well as low toxicity in 3- (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, this work proposes the cross-linked polydimethylsiloxane colloids as a novel non-ionic contrast agent for gastrointestinal magnetic resonance imaging. The experiments of nuclear magnetic resonance spectra and relaxation show that within the interface of the colloids, there are nuclear Overhauser effect and transient nuclear Overhauser effect (cross-relaxation). Regarding the longitudinal relaxation experiments of CH2CH2O segments of Tween 80, a two spins system is found and modeled well by the equation I Z − I 0 = S 0 ((1 − X) e − t D 1 − (1 + X) e − t T 1 ) which is deduced based on the transient nuclear Overhauser effect proposed by Solomon. The arbitrary constant X is additionally added with the initial conditions (Iz − I 0) t=0 = −2 XS 0 and (Sz − S 0) t=0 = −2 S 0. For the two spins system, D 1 and T 1 are corresponding to longitudinal relaxation times of the bound water and the CH2CH2O respectively. Concerning the transverse relaxation experiments of the CH2CH2O, they agree with the equation with three exponential decays, defined by three relaxation times, likely corresponding to three mechanisms. These mechanisms possibly are intramolecular and intermolecular dipole–dipole (DD) interactions and scalar coupling. Within the interface, hydrogen bonding causes the positive nuclear Overhauser effect of the CH2CH2O's nuclear magnetic resonance spectra, the transient nuclear Overhauser effect of the CH2CH2O's longitudinal relaxation experiments and the intermolecular dipole–dipole interactions of the CH2CH2O's transverse relaxation experiments. [ABSTRACT FROM AUTHOR]

Lovastatin is a drug of the statin group which possesses the ability to decrease low-density lipoprotein cholesterol level by the competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. There is a hypothesis that pharmacological features of statins depend on their location in cell membrane, but to the present day, there is a lack of information in literature on interactions of statins with the surface of the cell membrane in liquid media. Intermolecular complex of lovastatin with dodecylphosphocholine (DPC) and sodium dodecylsulfate (SDS) micelles was investigated by NMR and computational methods. The results of NMR experiments and molecular dynamics (MD) simulation data showed that lovastatin forms intermolecular complexes with models of cell membranes in water solution. Locations of lovastatin on model membranes were established by NOESY NMR data. Distinctions in their positions can explain differences in pharmacological properties of studied compound. [ABSTRACT FROM AUTHOR]

Protein NMR structure determination is one of the most extensively studied problems. Here, we adopt a novel method based on a matrix completion technique – the Riemannian approach – to rebuild the protein structure from the nuclear Overhauser effect distance restraints and the dihedral angle restraints. In comparison with the cyana method, the results generated via the Riemannian approach are more similar to the standard X‐ray crystallographic structures as a result of the simple but powerful internal calculation processing function. In addition, our results demonstrate that the Riemannian approach has a comparable or even better performance than the cyana method on other structural assessment metrics, including the stereochemical quality and restraint violations. The Riemannian approach software is available at: https://github.com/xubiaopeng/Protein_Recon_MCRiemman. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR) has the unique advantage of elucidating the structure and dynamics of biomolecules in solution at physiological temperatures, where they are in constant movement on timescales from picoseconds to milliseconds. Such motions have been shown to be critical for enzyme catalysis, allosteric regulation, and molecular recognition. With NMR being particularly sensitive to these timescales, detailed information about the kinetics can be acquired. However, nearly all methods of NMR-based biomolecular structure determination neglect kinetics, which introduces a large approximation to the underlying physics, limiting both structural resolution and the ability to accurately determine molecular flexibility. Here we present the Kinetic Ensemble approach that uses a hierarchy of interconversion rates between a set of ensemble members to rigorously calculate Nuclear Overhauser Effect (NOE) intensities. It can be used to simultaneously refine both temporal and structural coordinates. By generalizing ideas from the extended model free approach, the method can analyze the amplitudes and kinetics of motions anywhere along the backbone or side chains. Furthermore, analysis of a large set of crystal structures suggests that NOE data contains a surprising amount of high-resolution information that is better modeled using our approach. The Kinetic Ensemble approach provides the means to unify numerous types of experiments under a single quantitative framework and more fully characterize and exploit kinetically distinct protein states. While we apply the approach here to the protein ubiquitin and cross validate it with previously derived datasets, the approach can be applied to any protein for which NOE data is available. [ABSTRACT FROM AUTHOR]

The intermolecular interactions in a hybrid electrolyte based on various compositions of the ionic liquid N-methyl-N-propyl pyrrolidinium bis-fluorosulfonylimide (C3mpyrFSI), LiFSI salt and an ether-based additive, 1,2-dimethoxy ethane (DME), have been investigated using the HOESY (Heteronuclear Overhauser Effect SpectroscopY) NMR experiment. This NMR technique allows a quantification of the intermolecular interactions in ionic liquids (ILs) by measuring the cross-relaxation rate (σ) between different pairs of nuclei. Thereby, we compare the cross-relaxation rates between the cations, anions and DME in these hybrid electrolyte systems using 1H-7Li and 1H-19F HOESY experiments, and interpret the measured parameters in terms of ionic and molecular associations. The results give insights into the local coordination environment of the Li+ cations and their solvation by the FSI anions and DME.

In this work, the physical, transport and electrochemical properties of various electrolytic solutions containing the 1-propyl-1-methylpyrrolidinium bis[fluorosulfonyl]imide ([C3C1pyr][FSI]) mixed with the lithium bis[(trifluoromethyl)sulfonyl]imide (Li[TFSI]) over a wide range of compositions are reported as a function of temperature at atmospheric pressure. First, the ionicity, lithium transference number, and transport properties (viscosity and conductivity) as well as the volumetric properties (density and molar volume) were determined as a function of lithium salt concentration from 293 to 343 K. Second, the self-diffusion coefficient of each ion in solution was measured by nuclear magnetic resonance (NMR) spectroscopy with pulsed field gradients (PFG). Moreover, an analysis of the collected nuclear Overhauser effect (NOE) data along with ab initio and COSMO-RS calculations was conducted to depict intra and intermolecular neighbouring within the electrolytic mixtures. Based on this analysis, and as expected, all activation energies increase with the Li[TFSI] concentration in solution, and all activation energies were determined from the self-diffusion data for all ions. Interestingly, regardless of the composition in solution, these activation energies were similar, except for those determined for the [FSI]− anion. The activation energy of [FSI]− self-diffusion relatively decreases compared to the other ions as the lithium salt concentration increases. Furthermore, the lithium transference was strongly affected by the lithium salt concentration, reaching an optimal value and an ionicity of approximately 50 % at a molality close to 0.75 mol · kg−1. Finally, these electrolytes were used in lithium-ion batteries (i.e. Li/NMC and LTO/NMC), demonstrating a clear relationship between the electrolyte formulation, its transport parameters and battery performance. [ABSTRACT FROM AUTHOR]

At the catalytic site for the hydrolysis of cellulose the enzyme cellobiohydrolase Cel7A binds the enantiomers of the adrenergic beta‐blocker propranolol with different selectivity. Methyl‐to‐hydroxymethyl group modifications of propranolol, which result in higher affinity and improved selectivity, were herein studied by 1H,1H and 1H,13C scalar spin–spin coupling constants as well as utilizing the nuclear Overhauser effect (NOE) in conjunction with molecular dynamics simulations of the ligands per se, which showed the presence of all‐antiperiplanar conformations, except for the one containing a vicinal oxygen–oxygen arrangement governed by the gauche effect. For the ligand–protein complexes investigated by NMR spectroscopy using, inter alia, transferred NOESY and saturation‐transfer difference (STD) NMR experiments the S‐isomers were shown to bind with a higher affinity and a conformation similar to that preferred in solution, in contrast to the R‐isomer. The fact that the S‐form of the propranolol enantiomer is pre‐arranged for binding to the protein is also observed for a crystal structure of dihydroxy‐(S)‐propranolol and Cel7A presented herein. Whereas the binding of propranolol is entropy driven, the complexation with the dihydroxy analogue is anticipated to be favored also by an enthalpic term, such as for its enantiomer, that is, dihydroxy‐(R)‐propranolol, because hydrogen‐bond donation replaces the corresponding bonding from hydroxyl groups in glucosyl residues of the natural substrate. In addition to a favorable entropy component, albeit lesser in magnitude, this represents an effect of enthalpy‐to‐entropy compensation in ligand–protein interactions. Ligand–protein interactions: Conformational preferences of propranolol and dihydroxypropranolol in aqueous solvent were elucidated by NMR spectroscopy and MD simulations (see figure). [ABSTRACT FROM AUTHOR]

Abstract A theoretical and experimental study was performed on natural deep eutectic solvents (NADES) formed by lactic acid-glucose (LGH), citric acid-fructose (CFH) and citric acid-glucose (CGH). The presence of nuclear Overhauser effect (NOE) in the proton nuclear magnetic resonance (1H NMR) spectra of the NADES was studied. The spatial proximity between the NADES components was experimentally confirmed by the detection of multiple NOE effects in the dilutions analyzed. LGH showed the best outcome by partially maintaining its supramolecular structure throughout the dilutions. In order to rationalize the intermolecular interactions generated among the components, a theoretical study was performed using a density functional theory (DFT) computational method. A simplified dimeric model of the NADES was selected in order to achieve a rapid screening of the system searching for interactions between their constituents. In agreement with the experimental evidence, the calculations allowed to confirm the spatial proximity, by finding at least two hydrogen bonds between the components of every NADES. Highlights • The presence of nuclear Overhauser effect (NOE) in 1H NMR spectra of NADES was studied. • Spatial proximity between the NADES components was confirmed by the detection of multiple NOE effects. • LGH were the NADES that best holds its supramolecular structure throughout the dilutions. • Attenuation in the NOE effect were observed in solutions containing quercetin and LGH. • Theoretical study confirmed the existence of hydrogen bonding interactions for LGH, CGH and CFH. [ABSTRACT FROM AUTHOR]

Atorvastatin is a drug of the statin group which possesses the ability to decrease low-density lipoprotein cholesterol level by the competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase. There is a hypothesis that pharmacological properties of statins depend on their location in the cell membrane. Intermolecular complex of atorvastatin with dodecylphosphocholine (DPC) micelle was investigated by NMR and computational methods. The results of NMR experiments showed that atorvastatin forms molecular complex with model membrane in solution by penetrating a space between hydrocarbon chains of the DPC micelle. Analysis of obtained data in comparison with previously reported results for simvastatin, pravastatin, fluvastatin and cerivastatin showed that locations of statins in model membranes correlate with their pharmacological features, such as efficacy and risk of rhabdomyolysis. [ABSTRACT FROM AUTHOR]

The main problem in 31P magnetic resonance spectroscopy is a low signal-to-noise ratio (SNR) of spectra acquired with clinical magnetic resonance imaging (MRI) scanners. Using spin-spin phosphorus-proton (31P-1H) decoupling and heteronuclear Overhauser effect and taking into account the effect of the longitudinal relaxation time T1 on the SNR, the method for localization and excitation of the region of interest (Image Selected in vivo Spectroscopy pulse sequence) was optimized to increase the SNR in the 31P magnetic resonance spectra of the human brain to ~50% without increasing signal acquisition time. [ABSTRACT FROM AUTHOR]

The nuclear Overhauser effect (NOE) is a primary means to characterize intermolecular interactions using modern NMR spectroscopy. Multiple experiments measured using different mixing time can be used for quantifying NOE buildup and measuring cross-relaxation rates. However, this approach using conventional multi-dimensional NMR is time consuming. Hyperpolarization by dissolution dynamic nuclear polarization (D-DNP) can generate deviations from equilibrium spin polarization by orders of magnitude, thereby enhancing signals and allowing to characterize NOE build up in real-time. Since most small molecules can be hyperpolarized using D-DNP, this method is applicable to the study of intermolecular interactions between small molecules and macromolecules. This application is demonstrated using a model system for host-guest interactions including the third generation polyamidoamine dendrimer (G3 PAMAM) and the pharmaceutical phenylbutazone (PBZ). After mixing 1 H hyperpolarized PBZ with PAMAM, the NOE build up is directly observed at different sites of the dendrimer in series of one-dimensional NMR spectra. Cross-relaxation rates specific to individual source and target spins are determined from the build up curves. Further, the polarization enhancement is shown to be sufficiently large to allow identification of cross-peaks not observed in a conventional 2D-NOESY spectrum. The improved signal-to-noise ratio provided by hyperpolarization allows for characterizing the intermolecular interaction in an almost instantaneous measurement, opening an application to macromolecular and biomacromolecular NMR. [ABSTRACT FROM AUTHOR]

Abstract: Nuclear magnetic resonance spectroscopy is the prime tool to probe structure and dynamics of biomolecules at atomic resolution. A serious challenge for that method is the size limit imposed on molecules to be studied. Standard studies are typically restricted to ca. 30–40 kDa. More recent developments lead to spin relaxation measurements in methyl groups in single proteins or protein complexes as large as a mega‐Dalton, which directly allow the extraction of angular information or experiments with paramagnetic samples. However, these probes are all of indirect nature in contrast to the most intuitive and easy‐to‐interpret structural/dynamics restraint, the internuclear distance, which can be measured by nuclear Overhauser enhancement (NOE). Herein, we demonstrate time‐averaged distance measurements on the 360 kDa half proteasome from Thermoplasma acidophilium. The approach is based on exact quantification of the NOE (eNOE). Our findings open up an avenue for such measurements on very large molecules. These restraints will help in a detailed determination of conformational changes upon perturbation such as ligand binding. [ABSTRACT FROM AUTHOR]

In cryogenic dissolution NMR experiments, a substance of interest is allowed to rest in a strong magnetic field at cryogenic temperature, before dissolving the substance in a warm solvent, transferring it to a high-resolution NMR spectrometer, and observing the solution-state NMR spectrum. In some cases, negative enhancements of the 13 C NMR signals are observed, which have been attributed to quantum-rotor-induced polarization. We show that in the case of acetone (propan-2-one) the negative signal enhancements of the methyl 13 C sites may be understood by invoking conventional cross-relaxation within the methyl groups. The 1 H nuclei acquire a relative large net polarization through thermal equilibration in a magnetic field at low temperature, facilitated by the methyl rotation which acts as a relaxation sink; after dissolution, the 1 H magnetization slowly returns to thermal equilibrium at high temperature, in part by cross-relaxation processes, which induce a transient negative polarization of nearby 13 C nuclei. We provide evidence for this mechanism experimentally and theoretically by saturating the 1 H magnetization using a radiofrequency field pulse sequence before dissolution and comparing the 13 C magnetization evolution after dissolution with the results obtained from a conventional 1 H- 13 C cross relaxation model of the CH 3 moieties in acetone. [ABSTRACT FROM AUTHOR]