Transient Nuclear Overhauser Effect Research Articles

Feasibility of transient nuclear Overhauser effect imaging in brain at 7 T.

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. 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. 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. 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.

Cross-linked polydimethylsiloxane colloid as novel contrast agent for gastrointestinal magnetic resonance imaging: Transient nuclear Overhauser effect within the interface.

With good contrast in T1 and T2 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 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 - I0)t=0 = -2XS0 and (Sz - S0)t=0 = -2S0. For the two spins system, D1 and T1 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.

Geometry of Hydrogen Bonds in Liquid Ethanol Probed by Proton NMR Experiments.

Quantitative information of hydrogen bonding is crucial to our understanding of the structure and properties of associated liquids. Here, we outline a simple procedure to establish the geometry of hydrogen bonds in liquid ethanol using proton nuclear magnetic resonance (NMR) spectroscopy. We do so by exploiting differences in proton chemical shift values, that originate from the secondary isotope effect, to distinguish the methyl and hydroxyl group protons of CH3CH2OH from those of the deuterated CH3CD2OH in the 1H NMR spectra of mixtures of the two. This has allowed us to measure the ratios of the inter- to intramolecular distances between methyl to hydroxyl and methylene to hydroxyl protons using one-dimensional (1D) transient nuclear Overhauser effect NMR measurements as a molecular ruler. We model liquid ethanol by ab initio molecular dynamics simulations and identify all possible pairs of ethanol molecules in the ensemble that satisfied the NMR-determined inter- to intramolecular distance ratio criteria. For these pairs of ethanol molecules, we find the mean value of the hydrogen bonding distance, rOH···O, to be 1.93 Å and the value of the ∠HO···O angle to be 13.3°, thus effectively establishing the geometry of hydrogen bonds in liquid ethanol. An interesting observation that emerges from our study is the linear correlation between hydrogen bond distances and angles in ethanol.

Transient NOE enhancement in solid-state MAS NMR of mobile systems

It has been known that the heteronuclear cross-relaxation affects the dilute S spin magnetization along the longitudinal direction, causing an overshoot phenomenon for those mobile systems in spin-lattice relaxation rate measurements. Here, we analyze the Solomon equations for an I-S system and derive the transient cross relaxation effect as to when an overshoot phenomenon would take place and what the maximum enhancement could be at the time of the overshoot. In order to utilize such a transient nuclear Overhauser effect (NOE), we first time apply it to dynamic solid samples by inverting the 1H magnetization prior to the excitation of the S spin. It is found that the overshoot depends on the ratio of the I and S spin-lattice relaxation rates, i.e. RSS/RII. When RSS/RII≫1, the maximum enhancement factor for transient NOE could be larger than that obtained in steady-state NOE experiments. Furthermore, transient NOE appears to be more efficient in terms of sensitivity enhancement of dilute spins in solid-state NMR of mobile systems than the traditional cross polarization scheme whose efficiency is greatly compromised by molecular mobility. A sample of natural abundance l-isoleucine amino acid, in which the spin-lattice relaxation rates for the four methyl carbons are different, has been used to demonstrate sensitivity enhancement factors under various experimental schemes.

Band inversion amplifies 31 P-31 P nuclear overhauser effects: Relaxation mechanism and dynamic behavior of ATP in the human brain by 31 P MRS at 7 T.

To develop an improved method to measure the 31 P nuclear Overhauser effect (NOE) for evaluation of adenosine triphosphate (ATP) dynamics in terms of correlation time (τc ), and contribution of dipole-dipole (DD) and chemical shift anisotropy (CSA) mechanisms to T1 relaxation of ATP in human brain. The NOE of ATP in human brain was evaluated by monitoring changes in magnetization in the β-ATP signal following a band inversion of all downfield 31 P resonances. The magnetization changes observed were analyzed using the Bloch-McConnell-Solomon formulation to evaluate the relaxation and motion dynamic parameters that describe interactions of ATP with cellular solids in human brain tissue. The maximal transient NOE, observed as a reduction in the β-ATP signal, was 24 ± 2% upon band inversion of γ- and α-ATP, which is 2-3-fold higher than achievable by frequency-selective inversion of either γ- or α-ATP. The rate of 31 P-31 P cross relaxation (0.21 ± 0.02 s-1 ) led to a τc value of (9.1 ± 0.8) × 10-8 s for ATP in human brain. The T1 relaxation of β-ATP is dominated by CSA over the DD mechanism (60%: 40%). The band inversion method proved effective in amplifying 31 P NOE, and thus facilitating ATP τc and relaxation measurements. This technique renders ATP a potentially useful reporter molecule for cellular environments. Magn Reson Med 77:1409-1418, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

ChemInform Abstract: Isovanillyl Sweeteners. Synthesis, Conformational Analysis, and Structure-Activity Relationship of Some Sweet Oxygen Heterocycles.

New benzodioxin, benzodioxole, benzodioxepine and isoflavan analogues of the natural isovanillyl sweetener phyllodulcin have been synthesized and their sweetness assessed. Molecular-mechanics calculations on 15 members of the class of the isovanillyl sweet compounds indicated a preferential quasi-orthogonal orientation of the isovanillyl ring with respect to the heterocyclic ring. Experimental confirmation was obtained by a detailed study of transient NOE (nuclear Overhauser effect) experiments on 2-(3-hydroxy-4-methoxyphenyl)-1,4-benzodioxane. A theoretical treatment of these experiments is given. As, however, the energy barrier for the rotation of the isovanillyl ring around the bond linking it to the heterocyclic ring is low, geometrical parameters independent of this rotation were sought and an empirical correlation with sweetness potency established. The results are discussed in terms of the current hypotheses on the receptor shape.

NMR spectroscopy explained: simplified theory, applications and examples for organic chemistry and structural biology

NMR spectroscopy explained: simplified theory, applications and examples for organic chemistry and structural biology

The truncated driven NOE and 13C NMR sensitivity enhancement in magnetically-aligned bicelles

The truncated driven nuclear Overhauser effect (NOE) sequence is examined as a means of sensitivity enhancement in 13C NMR spectroscopy of magnetically-aligned bicelles consisting of 4.5:1 mixtures of DMPC (1,2-dimyristoyl- sn-glycero-3-phosphocholine) plus DHPC (1,2-dihexanoyl- sn-glycero-3-phosphocholine), with 1 mole% DMPE-PEG 2000 (1,2-dimyristoyl- sn-glycero-3-phosphoethanolamine- N-methoxy(polyethylene glycol)-2000). Steady-state NOE enhancements were observed at all carbon segments except the lipid carbonyls, but full NOE enhancements were obtained only for the most mobile carbon segments, specifically the choline quaternary methyls and terminal acyl chain methyls of both DMPC and DHPC, as well as the ethylene oxide segments of the PEG head group of DMPE-PEG 2000. Other carbon segments exhibited NOE enhancements that scaled with mobility as determined by transient NOE measurements combined with spin–lattice relaxation measurements. We conclude that the truncated driven NOE provides sensitivity enhancement complimentary to that yielded by cross-polarization techniques and for mobile membrane-associated species may be preferred for its robustness and ease of setup.

Elucidation of cross relaxation in liquids by two-dimensional N.M.R. spectroscopy

Two-dimensional N.M.R. spectroscopy is applied to the elucidation of cross relaxation pathways in liquids. The theory underlying two dimensional studies of cross relaxation and of transient nuclear Overhauser effects is developed. The influence of the correlation time of the molecular random process is investigated. It is found that in the limit of short correlation times (extreme narrowing limit) weak negative cross-peaks are observed. However, for long correlation times (spin diffusion limit) strong positive cross-peaks can be obtained. The technique appears particularly promising for the study of cross relaxation in macromolecules. Examples of intra- and intermolecular cross relaxation in the extreme narrowing limit are presented.

Measurement of the 13C spin–lattice relaxation time of the non-crystalline regions of semicrystalline polymers by a cp MAS-based method

The non-crystalline 13C spin–lattice relaxation times of atactic and isotactic polypropylene and those of an ethylene–1-octene copolymer of low crystallinity have been measured by classical inversion and saturation recovery methods as well as by a cp MAS-based pulse sequence. The latter is a saturation recovery-type sequence that involves cross-polarization. It samples preferentially the soft non-crystalline regions of semicrystalline polymers. The method is found to be useful in determining T 1C of the amorphous regions of semicrystalline iPP at room temperature. It is found that the atactic PP molecule and the non-crystalline iPP regions have the same average segmental relaxation rate. The T 1C of some of the carbons investigated was < T 1H and the experimental recovery curves showed complex exponential behavior from the contribution of a transient nuclear Overhauser effect (NOE) to the 13C magnetization. Moreover, the experimental data were fitted with a double exponential function obtained from solving the Solomon equations. The fitting leads to T 1C in very good agreement with the values obtained by classical inversion or saturation recovery sequences. The same T 1C value was obtained with the cp-based sequence when transient NOEs were eliminated by saturation of the proton magnetization during the delay period. The hexyl branches of the ethylene copolymer lead to an increased average backbone C–C intermolecular distance in the non-crystalline regions compared to those of the linear polyethylene chain and, thus, to a higher backbone methylene segmental mobility.

Two-dimensional vibrational spectroscopy. VIII. Infrared optical Kerr effect and two-color infrared pump–probe measurements

The infrared optical Kerr effect (IR-OKE) and two-color infrared pump–probe spectroscopies, which can be directly used to study intermolecular vibrational energy relaxation pathways, are theoretically studied. The IR-OKE method involves an intense IR pulse with controlled frequency to build up large population on a specific intramolecular vibrationally excited state. After a finite mixing time, which is also experimentally controlled, the time evolution of the nonequilibrium density matrix is detected by using the femtosecond optical Kerr effect measurement. Due to the nonequilibrium population distribution initially induced by the intensive infrared pulse, the measured OKE signal differs from that measured for a molecular system initially in thermal equilibrium state. Particularly, it is found that the deviation from the harmonic response can be specifically measured by using this method. By following the same procedure developed in this paper, the two-color IR pump–probe absorption spectroscopy is also considered and the corresponding nonequilibrium IR response function is theoretically investigated with a direct comparison with complementary IR-OKE response function. By using the perturbation theory, the corresponding response functions are obtained in terms of the molecular properties such as linear and nonlinear spatial derivatives of dipole and polarizability and cubic and quartic anharmonic coefficients. Also, it is emphasized that this method is conceptually quite similar to the transient nuclear Overhauser effect nuclear magnetic resonance spectroscopy.

Structure of [1.1]Ferrocenophanyllithium in the Solution and the Solid State. Absence of an Intramolecular [C−H−C]- Hydrogen Bond

[1.1]Ferrocenophanyllithium (1) is shown by dynamic NMR (DNMR) and isotopic perturbation to undergo a rapid intramolecular 1,12-proton transfer coupled with 1,12-lithium ion transfer. The first [C−H−C]- hydrogen bond previously reported to be present in 1 is shown by X-ray crystallography to be absent in the solid state. The 13C NMR spectrum of the bridge-labeled compound [1,12-13C2][1.1]ferrocenophanyl[1-6Li]lithium (6) in 2,5-dimethyltetrahydrofuran (DMTHF) displays a 1:1:1 triplet (1J(13C,6Li) = 4.0 Hz) showing that 6Li is bonded to C-1 and that 1 is monomeric. Transient nuclear Overhauser effects (tNOE's) measured in DEE-d10 in bridged monodeuterated 1 show that the bridges in 1 are syn and not anti to each other and that lithium is exo-coordinated to the anionic bridge carbon. The 1J(13C,1H) coupling constants show that the hybridization of the carbanionic carbon is intermediate between sp2 and sp3. Thus the solution and solid state structures of 1 are similar. UV−vis spectroscopy shows that 1 exists mainly as contact ion pairs (CIPs) in the temperature range −100 to +25 °C in THF, DMTHF, and diethyl ether (DEE). In dimethoxyethane (DME), 1 is mainly CIPs above +25 °C but is mainly separated ion pairs (SIPs) below −30 °C.

Measurement of spin-lattice relaxation times of 13C in organic solids

A transient nuclear Overhauser effect (NOE) makes measurements of the 13C spin-lattice relaxation times in organic solids complicated. Extended Solomon equations are applied in order to describe 13C spin-lattice relaxation with 1H r.f. field irradiation. Spin-lattice relaxation under r.f. irradiation is shown to be generally a triple-exponential process, but it can be reduced to be single-exponential under stronger r.f. field irradiation as well as in the absence of 1H initial magnetizations. Based on numerical calculations, the difference between spin-lattice relaxation curves obeying T 1 C < T 1 H and those obeying T 1 C < T 1 H is clearly indicated. The methyl group resonances in solid-state l-valine are examined, and the experimental results agree well with the theoretical results.

The use of CVFF and CFF91 force fields in conformational analysis of carbohydrate molecules. Comparison with AMBER molecular mechanics and dynamics calculations for methyl α-lactoside

The solution conformation of methyl α-lactoside has been studied through molecular mechanics calculations using the AMBER/Homans, CVFF and CFF91 force fields, and compared to NMR nuclear Overhauser data. Steady-state and transient nuclear Overhauser effects (NOEs) have been interpreted in terms of the ensemble average distribution of conformers. The NOEs have been analysed using the complete relaxation matrix approach for a rigid and isotropic motion model. The molecular mechanics calculations have been performed at two dielectric constants (i.e. ε = 1 and 80 debyes, or ε = r and 80 debyes) in an exhaustive way, and, in some cases, have been complemented by specific calculations at intermediate ε values. Relaxed energy maps and adiabatic surfaces have been generated for the different dielectric constants. The probability distribution of conformers has been estimated from these steric energy maps. Molecular dynamics simulations in vacuo have also been performed. Our results indicate that the β-(1 → 4) glycosidic linkage shows some fluctuations between three low-energy regions, although it spends about 90% of its time in the region close to the global minimum. The observed conformation of methyl α-lactoside seems to be closer to that predicted by CVFF, although the AMBER/Homans results are also in qualitative agreement with the experimental data.

Micellization and gelation of a triblock copolymer of oxyethylene and oxypropylene, E93P44E93, studied by 1H nuclear magnetic relaxation

1 H NMR longitudinal and transverse relaxation times have been measured as a function of temperature at 300 and 500 MHz for aqueous solutions of a triblock copolymer of oxyethylene (E) and oxypropylene (P), E93P44E93, encompassing non-micellar, micellar and gel phases. At the critical micelle temperature (c.m.t.), there was a marked transition in the relaxation times of the hydrophobic P block attributed to a change from well solvated mobile chains below the c.m.t. to a more restricted, concentrated micelle-core environment above the c.m.t. However no transition in the properties of the hydrophilic E block was observed at the c.m.t., indicating the continuation of a solvated, mobile chain structure. At the transition from a micelle solution to a structured gel, transitions were observed in the relaxation times of both E and P blocks, consistent with gel formation by close packing of micelles at a spacing determined by the excluded volume rather than the hydrodynamic volume. Transient nuclear Overhauser effects (NOE) indicated that in the micelles there was considerable interpenetration of the E and P blocks at the boundary. The relaxation times were analysed using a two-step correlation function. For the E block, the fast correlation time representing local segmental motions was little affected by the phase transitions, whereas the slow correlation time representing larger-scale motions was much more affected. For the P block, both fast and slow correlation times increased significantly on micellization.

Gelation of aqueous solutions of diblock and triblock copolymers of ethylene oxide and 1,2-butylene oxide studied by 1H nuclear magnetic relaxation

1 H NMR longitudinal and transverse relaxation times have been measured as a function of temperature at 300 and 500 MHz for aqueous solutions of diblock and triblock copolymers of ethylene oxide (E) and 1,2-butylene oxide (B), encompassing micellar sol and gel phases. At the phase transitions from a micelle to a gel structure, transitions were observed in the relaxation times of the E block, consistent with gel formation by close packing of micelles at a spacing determined by the thermodynamic radius rather than the hydrodynamic radius. Transient nuclear Overhauser effects indicated that in the micelles there was considerable interpenetration of the E and B blocks at the core/fringe boundary. The relaxation times were analysed using a two-step correlation function. For the E block, the fast correlation time representing local segmental motions was little affected by gelation, whereas the slow correlation time representing larger-scale motions was much more affected. Towards the lowest temperatures studied (< 10 °C), the relaxation times of the B block indicated incipient micelle dissociation.

Modeling of arabinofuranose and arabinan, II. Nmr and Conformational analysis of arabinobiose and arabinan

AbstractThe disaccharide arabinobiose (5‐O‐α‐L‐arabinofuranosyl‐α‐L‐arabinofuranose) constitutes the basic repeating structures found in such polysaccharides as arabinan or in the side chains of the hairy regions of pectins. The conformational behavior of aqueous arabinobiose has been investigated by high resolution nmr and computerized molecular modeling. The complete conformational analysis of the, disaccharide has been achieved with the MM3 molecular mechanics methods using the flexible residue method. In this study, both the puckering of the arabinofuranose, rings and the orientations about the glycosidic torsion angles ϕ, ψ, and ω; were considered. Some insights into conformational transitions were obtained through molecular dynamics simulation using the CHARMM force field. In parallel, transient nuclear Overhauser effects at 400.13 MHz and long‐range vicinal homonuclear and heteronuclear coupling constants have been measured. The theoretical nmr data were calculated taking into account all accessible conformations and using averaging methods for both slow and fast internal motions models. The data do not support a single conformational model, and only conformational averaging yields the excellent agreement between the observed and simulated parameters. Within the potential energy surfaces computed for the disaccharide, several low energy conformers can be identified. When these conformations are extrapolated to regular polysaccharide structures, they generate chains of arabinan displaying right‐ and left‐handed chirality and a wide range of repeating units per turn of helix. © 1994 John Wiley &amp; Sons, Inc.

Dynamic 13C−1H nuclear polarization of lipid methylene resonances applied to broadband proton‐decoupled in vivo13C MR spectroscopy of human breast and calf tissue

Dynamic nuclear polarization of the coupled 13C-1H spin system was studied for optimizing the signal-to-noise ratio of in vivo 13C MR spectra. In particular, the truncated driven and transient nuclear Overhauser effect (NOE) of the proton-decoupled 13C resonances from methylene carbons in vegetable oil and in human calf tissue was observed. Maximum in vivo NOE enhancements eta = 1.5 and 0.9 were found, respectively. Theoretical fits to the data yield 13C-1H cross-relaxation times in the order of 0.6 s. Significant signal enhancement over the whole in vivo 13C chemical shift range is obtained with minimum expense utilizing the NOE of the dipolar coupled 13C-1H spin system in addition to proton-decoupling. NOE-enhanced proton-decoupled in vivo 13C MR spectra were acquired within 17 min in volunteer examinations from the human breast and the calf. These spectra show well-resolved resonances of carbons in lipids and several other cellular compounds.

Dynamic response to hydration in a superabsorbing polymer studied by carbon-13 NOE and spin-lattice relaxation times

It is found that in superabsorbing hydrolyzed starch-g-poly(acrylonitrile), steady-state and transient nuclear Overhauser effect (NOE) and spin-lattice relaxation time measurements bring out the dynamic response to hydration. The NOE factor is seen to be sensitive to the hydration level. At low hydrations the NOE behavior is consistent with the process of preferential hydration in this polymer. The NOE does not reach the theetical maximum even when hydrated to 8.0 g/g. Selective 1 H irradiation experiments with MASS bring out the importance of interchain interactions between the pendent groups and starch units

Nuclear overhauser effect in coupled‐spin systems using selective perturbation

AbstractInterest in the nuclear Overhauser effect (NOE) has increased enormously in recent years because of its wide application to the structure determination of molecules in the liquid state, particularly large molecules, such as biomolecules. Most NOE studies are carried out in spin systems that exhibit splittings because of indirect spin‐spin (J) couplings, but the most common NMR analyses ignore I splitting. We focus attention on the presence of J coupling and particularly on selective perturbation of a transition of coupled spins. Both steady‐state and transient NOE have been calculated in closed form. There is a large multiplet effect that results from the direct pumping effect that is observed in the intensities, careful measurement of which requires the use of small‐angle pulses. The use of a 90° pulse obliterates the multiplet effect. As an extension, cross‐correlation effects in the three‐spin system and the three‐spin effect in NOE spectra also are discussed. A brief analysis of spin diffusion in a multiple‐spin system is also included.