Polarization Transfer Technique Research Articles

NMR spectroscopic investigations of transition metal complexes in organometallic and bioinorganic chemistry

AbstractThe field of coordination chemistry has evolved to intersect with organic chemistry and biochemistry, giving rise to the disciplines of organometallic and bioinorganic chemistry. Nuclear magnetic resonance (NMR) spectroscopy can be applied for characterizing transition metal complexes, spanning both diamagnetic and paramagnetic complexes prevalent in organometallic compounds and metalloproteins. This review offers a comprehensive overview of a wide variety of characterization techniques, ranging from basic 1H and 13C NMR spectroscopy to advanced methods such as heteronuclear experiments, polarization transfer techniques, relaxometry, and multidimensional NMR spectroscopy. The diverse array of NMR spectroscopic methods outlined here promises to enhance our comprehension of transition metal complexes, facilitating the development of innovative catalysts and therapeutics.

Novel approach to the global analysis of proton form factors in elastic electron-proton scattering

We present a method for the global analysis of elastic electron-proton scattering when combining data sets from experiments with different overall normalization uncertainties. The method is a modification of one employed by the NNPDF collaboration in the fitting of parton distribution data. This method is an alternative to the ‘penalty trick’ method traditionally employed in global fits to proton electric and magnetic form factors, while avoiding the statistical biases inherent in that approach. We discuss issues that arise when extending the method to nonlinear models. For data with Q2>1GeV2 we find relatively minor differences to traditional model fits when the normalization uncertainties from different experiments are correctly accounted for. We discuss implications of this method for the well-known discrepancy between the form factor ratio GE/GM extracted from the Rosenbluth and polarization transfer techniques. Published by the American Physical Society 2024

Skin, soap, and spaghetti: investigations of co-existing solid and liquid phases in organic materials using solid-state NMR with dynamics-based spectral editing

Abstract Solid-state NMR methods incorporating dynamics-based spectral editing have a remarkable versatility for resolving and separately characterizing co-existing solid and liquid phases or domains in biologically and technically relevant organic materials. While 13C spectra acquired under magic-angle spinning and 1H decoupling provide atomic resolution, the signal intensities obtained with the CP and INEPT polarization transfer techniques give qualitative information about dynamics. This mini-review covers the basics of translational and rotational motion of atoms and molecules in organic materials, theoretical aspects of the relations between C–H bond reorientation and CP and INEPT signal intensities, and applications of the methods to a broad range of heterogeneous materials comprising hydrated assemblies of surfactants, lipids, proteins, and/or carbohydrates.

Detecting water-protein chemical exchange in membrane-bound proteins/peptides by solid-state NMR spectroscopy

Water plays an important role in many essential biological processes of membrane proteins in hydrated lipid environments. In general, the 1H polarization transfers between water molecules and site-specific protons in proteins can be classified as coherent (via dipolar spin diffusion) and incoherent (via chemical exchange and nuclear Overhauser effect) transfers. Solid-state NMR is the technique of choice for studying such water-protein interactions in membrane-bound proteins/peptides through the detection of 1H polarization transfers from water to the proteins. These polarization transfer mechanisms often exist simultaneously and are difficult to quantify individually. Here, we review water-protein polarization transfer techniques in solid-state NMR, with a focus on the recent progress for the direct detection of site-specific kinetic water-protein chemical exchange processes on the sub-millisecond time scale in membrane-bound proteins. The measurements of the pure chemical exchange kinetics provide a unique opportunity to understand the role that water plays in the structure-function relationships of membrane-bound species at the water-bilayer interface. In addition, the perspective of chemical exchange saturation transfer (CEST) experiments in membrane-bound proteins/peptides is further discussed.

Retarded resonance Casimir\u2013Polder interaction of a uniformly rotating two-atom system

We consider a two-atom system uniformly moving through a circular ring at an ultra-relativistic speed and weakly interacting with the common quantum fields. Two kinds of fields are introduced here: a massive free scalar field and electromagnetic (EM) vector fields. The vacuum fluctuations of the quantum fields give rise to the resonance Casimir–Polder interaction (RCPI) in the system. Using the quantum master equation formalism, we calculate the second-order energy shift of the entangled states of the system. We find two major aspects of RCPI in a circular trajectory. The first one is the presence of the centripetal acceleration, which gives rise to non-thermality in the system, and secondly, due to the interaction with the above fields, the energy shift for RCPI is retarded in comparison with the massless scalar field. The retardation effect can die out by decreasing the centripetal acceleration and increasing the Zeeman frequency of the atoms. We also show that this phenomenon can be observed via the polarization transfer technique. The coherence time for the polarization transfer is calculated, which is different for the different fields.

Efficient transfer of DNP-enhanced 1 H magnetization to half-integer quadrupolar nuclei in solids at moderate spinning rate.

We show herein how the proton magnetization enhanced by dynamic nuclear polarization (DNP) can be efficiently transferred at moderate magic-angle spinning (MAS) frequencies to half-integer quadrupolar nuclei, S≥3/2, using the Dipolar-mediated Refocused Insensitive Nuclei Enhanced by Polarization Transfer (D-RINEPT) technique, in which a symmetry-based recoupling scheme built from adiabatic inversion 1 H pulses reintroduces the 1 H-S dipolar couplings, while suppressing the 1 H-1 H ones. The use of adiabatic pulses also improves the robustness to offsets and radiofrequency (rf)-field inhomogeneity. Furthermore, the efficiency of the polarization transfer is further improved by using 1 H composite pulses and continuous-wave irradiations between the recoupling blocks, as well as by manipulating the S satellite transitions during the first recoupling block. Furthermore, in the case of large 1 H-S dipolar couplings, the D-RINEPT variant with two pulses on the quadrupolar channel results in an improved transfer efficiency. We compare here the performances of this new adiabatic scheme with those of its parent version with single π pulses, as well as with those of PRESTO and CPMAS transfers. This comparison is performed using simulations as well as DNP-enhanced 27 Al, 95 Mo, and 17 O NMR experiments on isotopically unmodified γ-alumina, hydrated titania-supported MoO3 , Mg(OH)2 , and l-histidine·HCl·H2 O. The introduced RINEPT method outperforms the existing methods, both in terms of efficiency and robustness to rf-field inhomogeneity and offset.

Dipolar order mediated <sup>1</sup>H → <sup>13</sup>C cross-polarization for dissolution-dynamic nuclear polarization

Abstract. Magnetic resonance imaging and spectroscopy often suffer from a low intrinsic sensitivity, which can in some cases be circumvented by the use of hyperpolarization techniques. Dissolution-dynamic nuclear polarization offers a way of hyperpolarizing 13C spins in small molecules, enhancing their sensitivity by up to 4 orders of magnitude. This is usually performed by direct 13C polarization, which is straightforward but often takes more than an hour. Alternatively, indirect 1H polarization followed by 1H→13C polarization transfer can be implemented, which is more efficient and faster but is technically very challenging and hardly implemented in practice. Here we propose to remove the main roadblocks of the 1H→13C polarization transfer process by using alternative schemes with the following: (i) less rf (radiofrequency) power; (ii) less overall rf energy; (iii) simple rf-pulse shapes; and (iv) no synchronized 1H and 13C rf irradiation. An experimental demonstration of such a simple 1H→13C polarization transfer technique is presented for the case of [1-13C]sodium acetate, and is compared with the most sophisticated cross-polarization schemes. A polarization transfer efficiency of ∼0.43 with respect to cross-polarization was realized, which resulted in a 13C polarization of ∼8.7 % after ∼10 min of microwave irradiation and a single polarization transfer step.

Long Chain Branching Detection and Quantification in LDPE with Special Solvents, Polarization Transfer Techniques, and Inverse Gated 13C NMR Spectroscopy

Recent global demand of polyethylene was 187 billion pounds with 23% being low density polyethylene (LDPE). LDPE is used in a variety of applications including liners, consumer bags, heavy duty sac...

Recent Advances in Solid-State Nuclear Magnetic Resonance Spectroscopy.

The sensitivity of nuclear magnetic resonance (NMR) spectroscopy to the local atomic-scale environment offers great potential for the characterization of a diverse range of solid materials. Despite offering more information than its solution-state counterpart, solid-state NMR has not yet achieved a similar level of recognition, owing to the anisotropic interactions that broaden the spectral lines and hinder the extraction of structural information. Here, we describe the methods available to improve the resolution of solid-state NMR spectra and the continuing research in this area. We also highlight areas of exciting new and future development, including recent interest in combining experiment with theoretical calculations, the rise of a range of polarization transfer techniques that provide significant sensitivity enhancements, and the progress of in situ measurements. We demonstrate the detailed information available when studying dynamic and disordered solids and discuss the future applications of solid-state NMR spectroscopy across the chemical sciences.

Olive oil characterization and classification by 13C NMR with a polarization transfer technique: A comparison with gas chromatography and 1H NMR

In a previous work, we optimized and used a fast adiabatic 13C-INEPT (Insensitive Nuclei Enhanced by Polarization Transfer) experiment for the isotopomic analysis of olive oil samples, which allowed us quantifying individual fatty acids within triacylglycerols through multivariate linear regression models. The goal of this study was to validate these models and to evaluate the power of 13C-INEPT in the authentication of olive oils relative to gas chromatography (GC) and 1H NMR. In this respect, a new set of olive oil samples was analyzed by these three techniques. The analytical variables thus obtained as well as their corresponding long-term repeatability were compared. As a result, the reliability of the fatty acid quantification models was proven and the best classification of olive oils according to the altitude of the olive grove and to the morphological aspect (color) of the olives was achieved by means of 13C-INEPT.

Nanodiamond-enhanced MRI via in situ hyperpolarization

Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery and as highly biostable fluorescent markers for cellular tracking. Beyond optical techniques, however, options for noninvasive imaging of nanodiamonds in vivo are severely limited. Here, we demonstrate that the Overhauser effect, a proton–electron polarization transfer technique, can enable high-contrast magnetic resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra-low magnetic field. The technique transfers spin polarization from paramagnetic impurities at nanodiamond surfaces to 1H spins in the surrounding water solution, creating MRI contrast on-demand. We examine the conditions required for maximum enhancement as well as the ultimate sensitivity of the technique. The ability to perform continuous in situ hyperpolarization via the Overhauser mechanism, in combination with the excellent in vivo stability of nanodiamond, raises the possibility of performing noninvasive in vivo tracking of nanodiamond over indefinitely long periods of time.

A strategy for simultaneous determination of fatty acid composition, fatty acid position, and position-specific isotope contents in triacylglycerol matrices by 13C-NMR.

Triacylglycerols, which are quasi-universal components of food matrices, consist of complex mixtures of molecules. Their site-specific 13C content, their fatty acid profile, and their position on the glycerol moiety may significantly vary with the geographical, botanical, or animal origin of the sample. Such variables are valuable tracers for food authentication issues. The main objective of this work was to develop a new method based on a rapid and precise 13C-NMR spectroscopy (using a polarization transfer technique) coupled with multivariate linear regression analyses in order to quantify the whole set of individual fatty acids within triacylglycerols. In this respect, olive oil samples were analyzed by means of both adiabatic 13C-INEPT sequence and gas chromatography (GC). For each fatty acid within the studied matrix and for squalene as well, a multivariate prediction model was constructed using the deconvoluted peak areas of 13C-INEPT spectra as predictors, and the data obtained by GC as response variables. This 13C-NMR-based strategy, tested on olive oil, could serve as an alternative to the gas chromatographic quantification of individual fatty acids in other matrices, while providing additional compositional and isotopic information. Graphical abstract A strategy based on the multivariate linear regression of variables obtained by a rapid 13C-NMR technique was developed for the quantification of individual fatty acids within triacylglycerol matrices. The conceived strategy was tested on olive oil.

Proton-detected 3D (1)H/(13)C/(1)H correlation experiment for structural analysis in rigid solids under ultrafast-MAS above 60 kHz.

A proton-detected 3D (1)H/(13)C/(1)H chemical shift correlation experiment is proposed for the assignment of chemical shift resonances, identification of (13)C-(1)H connectivities, and proximities of (13)C-(1)H and (1)H-(1)H nuclei under ultrafast magic-angle-spinning (ultrafast-MAS) conditions. Ultrafast-MAS is used to suppress all anisotropic interactions including (1)H-(1)H dipolar couplings, while the finite-pulse radio frequency driven dipolar recoupling (fp-RFDR) pulse sequence is used to recouple dipolar couplings among protons and the insensitive nuclei enhanced by polarization transfer technique is used to transfer magnetization between heteronuclear spins. The 3D experiment eliminates signals from non-carbon-bonded protons and non-proton-bonded carbons to enhance spectral resolution. The 2D (F1/F3) (1)H/(1)H and 2D (13)C/(1)H (F2/F3) chemical shift correlation spectra extracted from the 3D spectrum enable the identification of (1)H-(1)H proximity and (13)C-(1)H connectivity. In addition, the 2D (F1/F2) (1)H/(13)C chemical shift correlation spectrum, incorporated with proton magnetization exchange via the fp-RFDR recoupling of (1)H-(1)H dipolar couplings, enables the measurement of proximities between (13)C and even the remote non-carbon-bonded protons. The 3D experiment also gives three-spin proximities of (1)H-(1)H-(13)C chains. Experimental results obtained from powder samples of L-alanine and L-histidine ⋅ H2O ⋅ HCl demonstrate the efficiency of the 3D experiment.

Synthesis and Cation Recognition Study of Novel Benzo Crown Ether Functionalized Enamine Derivatives

A novel series of benzo crown ether (dibenzo 18-crown-6 ether, benzo 18-crown-6 ether, and benzo 15-crown-5 ether) functionalized enamines derivatives from amino benzo crown ether (4-amino dibenzo 18-crown-6 ether, 4-amino benzo 18-crown-6 ether, 4-amino benzo 15-crown-5 ether) and substituted 3-(dimethylamino)-1-phenylprop-2-en-1-one compounds have been synthesized. All the synthesized compounds were characterized by infrared, 1H NMR, 13C NMR, distortionless enhancement polarization transfer, and mass and elemental analysis techniques. The cation recognition property for benzo crown ether enamine 8a was studied by absorption and fluorescence spectroscopy.

31P RINEPT MRSI and VBM reveal alterations in brain aging associated with major depression

PurposePhosphomono‐ and diesters, the major components of the choline peak in 1H magnetic resonance spectroscopy, are associated with membrane anabolic and catabolic mechanisms. With the refocused insensitive nuclei‐enhanced polarization transfer technique, these phospholipids are edited and enhanced in the 31P MR spectrum. In depressed patients, alterations of the choline peak and cerebral volume have been found, indicating a possible relation. Thus, combining MR phosphorous spectroscopy and volumetry in depressed patients seems to be a promising approach to detect underlying pathomechanisms.MethodsDepressed in‐patients were either treated with antidepressive medication or with electroconvulsive therapy and compared to matched healthy controls. 31P magnetic resonance spectroscopy imaging was conducted before and after the treatment phases. A 3D MRI dataset for volumetry was acquired in a dedicated 1H head coil.ResultsPhosphocholine and phosphoethanolamine were increased in depressed patients. Though patients responded to the treatments, phospholipids were not significantly altered. An increased age‐related gray matter loss in fronto‐limbic regions along with an altered relation of phosphomonoesters/phosphodiesters with age were found in depressed patients.DiscussionThe findings of increased phosphomonoesthers and an age*group interaction for gray matter volumes need further research to define the role of phospholipids in major depression and possible associations to gray matter loss. Magn Reson Med 73:1390–1400, 2015. © 2014 Wiley Periodicals, Inc.

Probing membrane protein structure using water polarization transfer solid-state NMR

Water plays an essential role in the structure and function of proteins, lipid membranes and other biological macromolecules. Solid-state NMR heteronuclear-detected 1H polarization transfer from water to biomolecules is a versatile approach for studying water–protein, water–membrane, and water–carbohydrate interactions in biology. We review radiofrequency pulse sequences for measuring water polarization transfer to biomolecules, the mechanisms of polarization transfer, and the application of this method to various biological systems. Three polarization transfer mechanisms, chemical exchange, spin diffusion and NOE, manifest themselves at different temperatures, magic-angle-spinning frequencies, and pulse irradiations. Chemical exchange is ubiquitous in all systems examined so far, and spin diffusion plays the key role in polarization transfer within the macromolecule. Tightly bound water molecules with long residence times are rare in proteins at ambient temperature. The water polarization-transfer technique has been used to study the hydration of microcrystalline proteins, lipid membranes, and plant cell wall polysaccharides, and to derive atomic-resolution details of the kinetics and mechanism of ion conduction in channels and pumps. Using this approach, we have measured the water polarization transfer to the transmembrane domain of the influenza M2 protein to obtain information on the structure of this tetrameric proton channel. At short mixing times, the polarization transfer rates are site-specific and depend on the pH, labile protons, sidechain conformation, as well as the radial position of the residues in this four-helix bundle. Despite the multiple dependences, the initial transfer rates reflect the periodic nature of the residue positions from the water-filled pore, thus this technique provides a way of gleaning secondary structure information, helix tilt angle, and the oligomeric structure of membrane proteins.

31P RINEPT MRSI and VBM reveal alterations in brain aging associated with major depression.

Phosphomono- and diesters, the major components of the choline peak in (1) H magnetic resonance spectroscopy, are associated with membrane anabolic and catabolic mechanisms. With the refocused insensitive nuclei-enhanced polarization transfer technique, these phospholipids are edited and enhanced in the (31) P MR spectrum. In depressed patients, alterations of the choline peak and cerebral volume have been found, indicating a possible relation. Thus, combining MR phosphorous spectroscopy and volumetry in depressed patients seems to be a promising approach to detect underlying pathomechanisms. Depressed in-patients were either treated with antidepressive medication or with electroconvulsive therapy and compared to matched healthy controls. (31) P magnetic resonance spectroscopy imaging was conducted before and after the treatment phases. A 3D MRI dataset for volumetry was acquired in a dedicated (1) H head coil. Phosphocholine and phosphoethanolamine were increased in depressed patients. Though patients responded to the treatments, phospholipids were not significantly altered. An increased age-related gray matter loss in fronto-limbic regions along with an altered relation of phosphomonoesters/phosphodiesters with age were found in depressed patients. The findings of increased phosphomonoesthers and an age*group interaction for gray matter volumes need further research to define the role of phospholipids in major depression and possible associations to gray matter loss.

Performance of RINEPT is amplified by dipolar couplings under ultrafast MAS conditions

The refocused insensitive nuclei enhanced by polarization transfer (RINEPT) technique is commonly used for heteronuclear polarization transfer in solution and solid-state NMR spectroscopy. Suppression of dipolar couplings, either by fast molecular motions in solution or by a combination of MAS and multiple pulse sequences in solids, enables the polarization transfer via scalar couplings. However, the presence of unsuppressed dipolar couplings could alter the functioning of RINEPT, particularly under fast/ultrafast MAS conditions. In this study, we demonstrate, through experiments on rigid solids complemented by numerical simulations, that the polarization transfer efficiency of RINEPT is dependent on the MAS frequency. In addition, we show that heteronuclear dipolar coupling is the dominant factor in the polarization transfer, which is strengthened by the presence of 1H–1H dipolar couplings. In fact, the simultaneous presence of homonuclear and heteronuclear dipolar couplings is the premise for the polarization transfer by RINEPT, whereas the scalar coupling plays an insignificant role under ultrafast MAS conditions on rigid solids. Our results additionally reveal that the polarization transfer efficiency decreases with the increasing duration of RF pulses used in the RINEPT sequence.

Altered phospholipid metabolism in schizophrenia: A phosphorus 31 nuclear magnetic resonance spectroscopy study

Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naïve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia.

Improve the selectively refocused INEPT pulse sequence for detecting phosphomonoesters and phosphodiesters

In application of the (31)P selectively refocused insensitive nuclei enhanced polarization transfer (srINEPT) technique to the detection of phosphomono- and diesters in tissues, homonuclear couplings between the CH(2)O protons and the NCH(2) protons seriously attenuate the sensitivity. These couplings can be conventionally removed by two soft 180° pulses in the (1)H evolution period which selectively invert the NCH(2) magnetizations. However, the srINEPT pulse sequence can be simplified by replacing the pulse train "soft 180°-hard 180°-soft 180°" with a single soft 180° pulse that selectively inverts the CH(2)O magnetizations. Theoretical analysis in this study demonstrates the correctness of this approach in principle. Validation on a milk phantom allowed us to investigate and discuss advantages and disadvantages of the proposed srINEPT with respect to the original srINEPT. Furthermore, comparison of different selective pulses made it possible to demonstrate that the proposed srINEPT experiment is not sensitive to errors in pulse length, offset, and B(1) field strength of the selective pulse when ReBurp pulse is used for selective refocusing.