Consequences of Xe–H Cross Relaxation in Aqueous Solutions

We have investigated the transfer of polarization from ¹²⁹Xe to solute protons in aqueous solutions to determine the feasibility of using hyperpolarized xenon to enhance ¹H sensitivity in aqueous systems at or near room temperatures. Several solutes, each of different molecular weight, were dissolved in deuterium oxide and although large xenon polarizations were created, no significant proton signal enhancement was detected in -tyrosine, α-cyclodextrin, β-cyclodextrin, apomyoglobin, or myoglobin. Solute-induced enhancement of the ¹²⁹Xe spin–lattice relaxation rate was observed and depended on the size and structure of the solute molecule. The significant increase of the apparent spin–lattice relaxation rate of the solution phase ¹²⁹Xe by α-cyclodextrin and apomyoglobin indicates efficient cross relaxation. The slow relaxation of xenon in β-cyclodextrin and -tyrosine indicates weak coupling and inefficient cross relaxation. Despite the apparent cross-relaxation effects, all attempts to detect the proton enhancement directly were unsuccessful. Spin–lattice relaxation rates were also measured for Boltzmann ¹²⁹Xe in myoglobin. The cross-relaxation rates were determined from changes in ¹²⁹Xe relaxation rates in the α-cyclodextrin and myoglobin solutions. These cross-relaxation rates were then used to model ¹H signal gains for a range of ¹²⁹Xe to ¹H spin population ratios. These models suggest that in spite of very large ¹²⁹Xe polarizations, the ¹H gains will be less than 10% and often substantially smaller. In particular, dramatic ¹H signal enhancements in lung tissue signals are unlikely.     

Intermolecular dipole-dipole relaxation of (129)Xe dissolved in water

Intermolecular (129)Xe-(1)H nuclear Overhauser effects and (129)Xe longitudinal relaxation time measurements were used to demonstrate that the dipole-dipole coupling is the dominant relaxation mechanism for (129)Xe in water, at room temperature. (129)Xe-(1)H cross-relaxation rates were derived to be sigma(XeH) approximately 3.2 +/- 0.3 x 10(-3) s(-1), independent of xenon pressure (in the range of 1-10 bar) and of the presence of oxygen. Corresponding xenon-proton internuclear distances were calculated to be 2.69 +/- 0.12 A. Using the magnitude of the dipole-dipole coupling and the spin density ratio between dissolved xenon and bulk water, it is estimated that (129)Xe-(1)H spin polarization-induced nuclear Overhauser effects would yield little net proton signal enhancement in water.     

Intermolecular Dipole–Dipole Relaxation of Xe Dissolved in Water

Intermolecular ¹²⁹Xe–¹H nuclear Overhauser effects and ¹²⁹Xe longitudinal relaxation time measurements were used to demonstrate that the dipole–dipole coupling is the dominant relaxation mechanism for ¹²⁹Xe in water, at room temperature. ¹²⁹Xe–¹H cross-relaxation rates were derived to be ς_XeH 3.2 ± 0.3 × 10⁻³ s⁻¹, independent of xenon pressure (in the range of 1–10 bar) and of the presence of oxygen. Corresponding xenon–proton internuclear distances were calculated to be 2.69 ± 0.12 Å. Using the magnitude of the dipole–dipole coupling and the spin density ratio between dissolved xenon and bulk water, it is estimated that ¹²⁹Xe–¹H spin polarization-induced nuclear Overhauser effects would yield little net proton signal enhancement in water.     

129Xe and131Xe NMR of xenon on silica surfaces at 77 K

Little is known about¹²⁹Xe NMR spectral features and spin-lattice relaxation behavior, and the dynamics of xenon atoms, for xenon adsorbed on solid surfaces at cryogenic temperatures (≤77 K), where exchange with gas-phase atoms is not a significant complication. We report¹²⁹Xe NMR experiments at 9,4 T that provide such information for xenon adsorbed onto the hydroxylated surface of a number of microporous silica samples at 77 K. A convenient design for these cryogenic experiments is described. Dynamics of surface-adsorbed xenon atoms on the time scale of seconds can be observed by¹²⁹Xe NMR hole-burning experiments; much slower dynamics occurring over hours and days are evidenced from changes with time of the¹²⁹Xe NMR chemical shifts. The peak maxima occur in the region ca. 180–316 ppm, considerably downfield of¹²⁹Xe shifts previously reported on surfaces at higher temperatures, and closer to the shift of xenon bulk solid (316.4±1 ppm). The¹²⁹Xe spin-lattice relaxation timesT ₁ range over five orders of magnitude; possible explanations for both nonexponential relaxation behavior and extremely shortT ₁ values (35 ms) are discussed. Preliminary¹³¹Xe and¹H NMR results are presented, as well as a method for greatly increasing the sensitivity of¹²⁹Xe NMR detection at low temperatures by using closely-spaced trains of rf pulses.     

Nuclear spin resonance of (129)Xe doped with O(2)

Spin-lattice relaxation of (129)Xe nuclei in solid natural xenon has been investigated in detail over a large range of paramagnetic O(2) impurity concentrations. Direct measurements of the ground state magnetic properties of the O(2) are difficult because the ESR (electron spin resonance) lines of O(2) are rather unstructured, but NMR measurements in the liquid helium temperature region (1.4-4 K) are very sensitive to the effective magnetic moments associated with the spin 1 Zeeman levels of the O(2) molecules and to the O(2) magnetic relaxation. From these measurements, the value of the D[Sz(2)-(1/3)S(2)] spin-Hamiltonian term of the triplet spin ground state of O(2) can be determined. The temperature and magnetic field dependence of the measured paramagnetic O(2)-induced excess line width of the (129)Xe NMR signal agree well with the theoretical model with the spin-Hamiltonian D=0.19 meV (2.3 K), and with the reasonable assumption that the E[S(x)(2)-S(y)(2)] spin-Hamiltonian term is close to 0 meV. An anomalous temperature dependence between 1.4 K and 4.2K of the (129)Xe spin-lattice relaxation rate, T(1n)(-1)(T), is also accounted for by our model. Using an independent determination of the true O(2) concentration in the Xe-O(2) solid, the effective spin lattice relaxation time (which will be seen to be transition dependent) of the O(2) at 2.3 K and 0.96 T is determined to be approximately 1.4 x 10(-8)s. The experimental results, taken together with the relaxation model, suggest routes for bringing highly spin-polarized (129)Xe from the low temperature condensed phase to higher temperatures without excessive depolarization.     

Hyperpolarized (131)Xe NMR spectroscopy

Hyperpolarized (hp) (131)Xe with up to 2.2% spin polarization (i.e., 5000-fold signal enhancement at 9.4 T) was obtained after separation from the rubidium vapor of the spin-exchange optical pumping (SEOP) process. The SEOP was applied for several minutes in a stopped-flow mode, and the fast, quadrupolar-driven T(1) relaxation of this spin I = 3/2 noble gas isotope required a rapid subsequent rubidium removal and swift transfer into the high magnetic field region for NMR detection. Because of the xenon density dependent (131)Xe quadrupolar relaxation in the gas phase, the SEOP polarization build-up exhibits an even more pronounced dependence on xenon partial pressure than that observed in (129)Xe SEOP. (131)Xe is the only stable noble gas isotope with a positive gyromagnetic ratio and shows therefore a different relative phase between hp signal and thermal signal compared to all other noble gases. The gas phase (131)Xe NMR spectrum displays a surface and magnetic field dependent quadrupolar splitting that was found to have additional gas pressure and gas composition dependence. The splitting was reduced by the presence of water vapor that presumably influences xenon-surface interactions. The hp (131)Xe spectrum shows differential line broadening, suggesting the presence of strong adsorption sites. Beyond hp (131)Xe NMR spectroscopy studies, a general equation for the high temperature, thermal spin polarization, P, for spin I ≥ 1/2 nuclei is presented.     

NMR Study of Laser polarized ~(129) Xe in Low Pressure Natural Xenon Gas

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A rapid and precise probe for measurement of liquid xenon polarization

The relaxation time of liquid (129)Xe is very long (>15 min) and the signal at thermal equilibrium is weak. Therefore, determination of the absolute polarization enhancement of hyperpolarized (129)Xe by direct measurement is tedious. We demonstrate a fast and precise alternative, based on the dipolar field created by liquid hyperpolarized (129)Xe contained in a cylindrical sample tube. The dipolar field is homogeneous in the bulk of the tube and adds to the external field, causing a shift in the Larmor frequencies of all nuclear spins. We show that the frequency shift of the proton in CHCl(3) (chloroform), which dissolves homogeneously in xenon over a fairly broad temperature range, is an excellent probe for (129)Xe polarization. Frequency measurements are precise and the experiment is much faster than by direct measurement. Furthermore the (129)Xe polarization is minimally disturbed since no rf pulses are applied directly to (129)Xe and since chloroform is a fairly weak source of (129)Xe relaxation. The experiments are reproducible and require only standard NMR instrumentation.     

NMR spin-lattice relaxation of the129Xe nucleus of xenon gas dissolved in various isotropic liquids

The spin-lattice relaxation time of the¹²⁹Xe nucleus of natural xenon gas dissolved in various isotropic liquids, acetonitrile, benzene, carbon tetrachloride and cyclohexane, was studied as a function of temperature at the magnetic fields of 9.4 and 4.7 T. The utilization of hydrogenated and deuterated benzene and cyclohexane reveals that the intermolecular¹²⁹Xe-¹H dipole-dipole interaction constitutes an important relaxation mechanism in hydrogenated solvents. According to this interpretation the interaction is rather strongly temperature-dependent, and increases with increasing temperature. An important observation of an experimental nature is also noted, namely convective flow present in non-spinning sample tubes at elevated temperatures disturbs inversion-recovery measurements and leads to erroneous and unreliable relaxation time values.     

NMR Study of Laser-polarized 129Xe in Low Pressure Natural Xenon Gas

The NMR signal from the laser-polarized t29 Xe in low-pressure natural xenon gas has been observed with a Bruker WP-80SY NMR spectrometer. The laser-polarized 129 Xe was produced by the method of laser pumping and spin exchange in a magnetic field of 1.87 Tesla. It is obtained experimentally that the nuclear spin relaxation rate 1/T1 of laser-polarized 129Xe are (4.03±1.97)×10-3/see～(2.21±0.78)×10-3/see in the range of the 3.33×103 Pa～8.29×104 Pa Xe gas pressures, the apparent wall relaxation rate 1/Tw* =(1.98±0.18)×10-3/see, and the relaxation rate coefficient C of 133Cs-129Xe spin exchange is (2.81±0.74)×10-16 em3/sec.     

Spin-diffusion couples proton relaxation rates for proteins in exchange with a membrane interface

Changes in nuclear spin-lattice relaxation rates that are induced by a freely diffusing paramagnetic relaxation agent are examined for a protein in solution and compared to the case where the protein binds to a membrane. In the solution case, the intramolecular cross-relaxation rates are modest and large differences are observed in the oxygen induced protein–proton relaxation rates. In the case where a dynamic equilibrium between solution and membrane-bound environments is established, the intramolecular ¹H cross-relaxation rates for the protein protons increase dramatically because of the slow reorientational motion in the membrane-bound environment. As a consequence, all protein protons relax with nearly the same spin-lattice relaxation rate constants when bound to the membrane, and site specific relaxation effects of the diffusing paramagnet are suppressed. Slowly reorienting sites or rotationally immobilized sites sampled by observable molecules in vivo will demonstrate similar relaxation leveling effects.     

T1-relaxation of 129Xe on metal single crystal surfaces-multilayer experiments on iridium and monolayer considerations

The surface of a typical laboratory single crystal has about 10(15) surface atoms or adsorption sites, respectively, and is thus far out of reach for conventional NMR experiments using thermal polarization. It should however be in reach for NMR of adsorbed laser polarized (hyperpolarized) 129Xe, which is produced by spin transfer from optically pumped rubidium. With multilayer experiments of xenon adsorbed on an iridium surface we do not only demonstrate that monolayer sensitivity has been obtained, we also show that such surface experiments can be performed under ultra high vacuum conditions with the crystal being mounted in a typical surface analysis chamber on a manipulator with far-reaching sample heating and cooling abilities. With only four spectra summed up we present an NMR signal from at most 4x10(14) atoms of 129Xe, four layers of naturally abundant xenon, respectively. The fact that no monolayer signal has been measured so far is explained by a fast Korringa relaxation due to the Fermi contact interaction of the 129Xe nuclei with the electrons of the metal substrate. T(1)-relaxation times in the order of several ms have been calculated using all electron density functional theory for several metal substrates.     

Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe

The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the (129)Xe chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce (129)Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the (129)Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall (129)Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed.     

1H and 129Xe NMR absorption line shapes in the presence of highly polarized and concentrated xenon solutions in high magnetic field

The presence of highly concentrated dissolved laser-polarized xenon (approximately 1mol/L, polarization up to 0.2) induces numerous effects on proton and xenon NMR spectra. We show that the proton signal enhancements due to (129)Xe-(1)H cross-relaxation (SPINOE) and overall shifts of the proton resonances due to the average dipolar shift created by the intense xenon magnetization are correlated. Protons behave as very useful sensors of the xenon magnetization. Indeed the xenon resonances exhibit many features such as superimposition of narrow lines on the main resonance due to clustering effects, or such as a polarization-dependent line broadening that is tentatively assigned to the effects of temperature fluctuations that decorrelate some distant dipolar field effects from local interactions, transforming xenon spins from "like" to "unlike" spins. These spectral features make difficult the determination of the average dipolar field by means of the xenon resonance but have interesting consequences on the heteronuclear polarization transfer experiment in Hartmann-Hahn conditions (SPIDER).     

Relaxation behavior of laser-polarized (129)Xe gas: size dependency and wall effect of the T(1) relaxation time in glass and gelatin bulbs

Size dependency of the relaxation time T(1) was measured for laser-polarized (129)Xe gas encapsulated in different sized cavities made by glass bulbs or gelatin capsules. The use of laser-polarized gas enhances the sensitivity a great deal, making it possible to measure the longer (129)Xe relaxation time in quite a short time. The size dependency is analyzed on the basis of the kinetic theory of gases and a relationship is derived in which the relaxation rate is connected with the square inverse of the diameter of the cavity. Such an analysis provides a novel parameter which denotes the wall effect on the relaxation rate when a gas molecule collides with the surface once in a second. The relaxation time of (129)Xe gas is also dependent on the material which forms the cavity. This dependency is large and the relaxation study using polarized (129)Xe gas is expected to offer important information about the state of the matter of the cavity wall.     

13C- and 1H-NMR Relaxation Investigation of a Polyciclic Nitrogen Compound: 3,3-Dimethyl-1,5-diphenyl-9-hydroxy-bispidinium Iodide

The rigid polycyclic nitrogen compound was considered as a test for the reliability of internuclear distances calculated by ¹H-NMR spin-lattice relaxation rates. The ‘isotropic’ motional correlation time was calculated from ¹³C relaxation rates (τ_C = 0.11 ns at 298 K). Dipolar cross-relaxation rates were calculated by measuring non-, mono- and double-selective proton spin-lattice relaxation rates. All the experimental relaxation rates were thoroughly accounted for by dipolar pairwise interactions. Only at high temperatures a certain contribution from the spin rotational mechanism was apparent.     

Proton NMR relaxation of adsorbed water in gelatin and collagen

The dependence of the water self-diffusion coefficients as well as of the proton spin-lattice and spin-spin relaxation rates on the concentration have been studied in the gelatin-water system and in hydrated native collagen. The bound and free water fractions and the corresponding spin-spin and spin-lattice relaxation rates have been determined within the multi-phase water proton exchange model. Various theoretical models for the water proton cross-relaxation to the biopolymer have been studied and the results compared with the observed Larmor frequency dependence of the water proton spin-lattice relaxation rate.     

Field-cycling NMR investigations of (13)C-(1)H cross-relaxation and cross-polarisation: the nuclear solid effect and dynamic nuclear polarisation

A field-cycling NMR investigation of (1)H-(13)C polarisation transfer using cross-relaxation and the nuclear solid effect (NSE) is described. Dynamic nuclear polarisation (DNP) of the (13)C spins is observed when forbidden transitions are driven by r.f. irradiation at the sum and difference Larmor frequencies of the two nuclei. When the (1)H spins are pre-polarised, a significant transfer of polarisation to the (13)C nuclei is achieved in a time short compared with the spin-lattice relaxation time of (13)C. The cross-polarisation arising from the NSE is studied as a function of B-field and time. These results are compared with the solutions of the differential equations that govern the coupled system of (1)H-(13)C spins. The effects of cross-relaxation are incorporated into the model for the first time and good agreement between theory and experiment is obtained. The experiments have been conducted at 20K on a (13)C-enriched sample of benzoic acid.     

Temperature response of 129Xe depolarization transfer and its application for ultrasensitive NMR detection

Trapping xenon in functionalized cryptophane cages makes the sensitivity of hyperpolarized (HP) 129Xe available for specific NMR detection of biomolecules. Here, we study the signal transfer onto a reservoir of unbound HP xenon by gating the residence time of the nuclei in the cage through the temperature-dependant exchange rate. Temperature changes larger than approximately 0.6 K are detectable as an altered reservoir signal. The temperature response is adjustable with lower concentrations of caged xenon providing more sensitivity at higher temperatures. Ultrasensitive detection of functionalized cryptophane at 310 K is demonstrated with a concentration of 10 nM, corresponding to a approximately 4000-fold sensitivity enhancement compared to conventional detection. This makes HPNMR capable of detecting such constructs in concentrations far below the detection limit of benchtop uv-visible light absorbance.     

NMR of Xe on CO/Ir(1 1 1) and on multilayer Xe/Ir(1 1 1)

Nuclear magnetic resonance (NMR) is performed on monolayer (ML) amounts of adsorbed ¹²⁹Xe on a single crystal substrate. The inherently low sensitivity of NMR is overcome by using highly nuclear spin polarized ¹²⁹Xe that has been produced by optical pumping. A polarization of 0.8 is regularly achieved which is 10⁵ times the thermal (Boltzmann) polarization. The experiments are performed with a constant flux of xenon atoms impinging on the surface, typically 4 ML/s. The chemical shift (σ) of ¹²⁹Xe is highly sensitive to the Xe local environment. We measured profoundly different shifts for the Xe bulk, for the surface of the Xe bulk, and for Xe on CO/Ir(1 1 1). The growth of the bulk is seen in a phase transition like change of σ as a function of temperature at constant Xe flux. At temperatures where no bulk forms at a flux of 4 ML/s, the xenon exchange rate was measured by a spin inversion/recovery method. The exchange time of Xe is found to be 0.24 s at 63.4 K and 64.4 K and somewhat longer at 61.2 K. An analysis is given involving the desorption out of the second layer and fast mixing of first and second layer atoms at these temperatures.