129Xe NMR Chemical Shift Research Articles

Encapsulation of xenon by bridged resorcinarene cages with high 129Xe NMR chemical shift and efficient exchange dynamics

Encapsulation of xenon by bridged resorcinarene cages with high 129Xe NMR chemical shift and efficient exchange dynamics

Analysis of NMR Adsorption Isotherms of Zeolite ZSM-5: Adsorption Profiles Derived from the Pressure and Temperature Dependences of 129Xe NMR Chemical Shift and Signal Intensity.

129Xe NMR spectroscopy of nanomaterials, such as zeolites, can provide valuable information on the nanostructure and physicochemical properties of adsorption. In the present study the pressure and temperature dependences of the 129Xe NMR chemical shift and the signal intensity were investigated in detail with a zeolite ZSM-5. The pressure dependence of the signal intensity at constant temperature was analyzed based on the Langmuir and Dubinin-Radushkevich (D-R) models, from which the thermodynamic parameters and energetic profiles of adsorption were obtained together with information concerning the nanospace size. From this isotherm analysis the coverage, θ, was calculated and used for isotherm analysis of the chemical shift. The θ dependence of the chemical shift was successfully fitted by an exponential function, and the results were discussed in relation to the chemical shift at zero coverage, that at full coverage and the curvature of the exponential function. The chemical shift data reported with the zeolites NaA and KA, where separated signals were observed for the different number of encapsulated Xe atoms in the α cage, were analyzed and discussed collectively.

Monomeric Cryptophane with Record-High Xe Affinity Gives Insights into Aggregation-Dependent Sensing.

Cryptophane host molecules provide ultrasensitive contrast agents for 129Xe NMR/MRI. To investigate key features of cryptophane-Xe sensing behavior, we designed a novel water-soluble cryptophane with a pendant hydrophobic adamantyl moiety, which has good affinity for a model receptor, beta-cyclodextrin (β-CD). Adamantyl-functionalized cryptophane-A (AFCA) was synthesized and characterized for Xe affinity, 129Xe NMR signal, and aggregation state at varying AFCA and β-CD concentrations. The Xe-AFCA association constant was determined by fluorescence quenching, KA = 114,000 ± 5000 M-1 at 293 K, which is the highest reported affinity for a cryptophane host in phosphate-buffered saline (pH 7.2). No hyperpolarized (hp) 129Xe NMR peak corresponding to AFCA-bound Xe was directly observed at high (100 μM) AFCA concentration, where small cryptophane aggregates were observed, and was only detected at low (15 μM) AFCA concentration, where the sensor remained fully monomeric in solution. Additionally, we observed no change in the chemical shift of AFCA-encapsulated 129Xe after β-CD binding to the adamantyl moiety and a concomitant lack of change in the size distribution of the complex, suggesting that a change in the aggregation state is necessary to elicit a 129Xe NMR chemical shift in cryptophane-based sensing. These results aid in further elucidating the recently discovered aggregation phenomenon, highlight limitations of cryptophane-based Xe sensing, and offer insights into the design of monomeric, high-affinity Xe sensors.

Investigation of grafted mesoporous silicon sponge using hyperpolarized 129Xe NMR spectroscopy

Abstract

Cryptophane Nanoscale Assemblies Expand 129Xe NMR Biosensing.

Cryptophane-based biosensors are promising agents for the ultrasensitive detection of biomedically relevant targets via 129Xe NMR. Dynamic light scattering revealed that cryptophanes form water-soluble aggregates tens to hundreds of nanometers in size. Acridine orange fluorescence quenching assays allowed quantitation of the aggregation state, with critical concentrations ranging from 200 nM to 600 nM, depending on the cryptophane species in solution. The addition of excess carbonic anhydrase (CA) protein target to a benzenesulfonamide-functionalized cryptophane biosensor (C8B) led to C8B disaggregation and produced the expected 1:1 C8B-CA complex. C8B showed higher affinity at 298 K for the cytoplasmic isozyme CAII than the extracellular CAXII isozyme, which is a biomarker of cancer. Using hyper-CEST NMR, we explored the role of stoichiometry in detecting these two isozymes. Under CA-saturating conditions, we observed that isozyme CAII produces a larger 129Xe NMR chemical shift change (δ = 5.9 ppm, relative to free biosensor) than CAXII (δ = 2.7 ppm), which indicates the strong potential for isozyme-specific detection. However, stoichiometry-dependent chemical shift data indicated that biosensor disaggregation contributes to the observed 129Xe NMR chemical shift change that is normally assigned to biosensor-target binding. Finally, we determined that monomeric cryptophane solutions improve hyper-CEST saturation contrast, which enables ultrasensitive detection of biosensor-protein complexes. These insights into cryptophane-solution behavior support further development of xenon biosensors, but will require reinterpretation of the data previously obtained for many water-soluble cryptophanes.

Exploring the Complex Porosity of Transition Aluminas by 129Xe NMR Spectroscopy

Crystalline mesoporous γ-, δ-, and θ-alumina samples with complex porosity and various surface areas (70 to 330 m2/g) were characterized by 129Xe NMR spectroscopy and nitrogen adsorption. Experimental conditions have been optimized to measure 129Xe NMR chemical shifts independent of the nature of the surface and solely dependent on the pore size. Xenon adsorption constants have been determined from xenon adsorption isotherms and from the fit of the chemical shift versus volume to surface ratio (V/S) curves with a simple exchange model. The discrepancy observed between those values has been attributed to the rugosity of the alumina pore surface. A direct correlation between the observed chemical shift and the alumina pore diameter was obtained for the whole series of alumina samples.

A "Smart" ¹²⁸Xe NMR Biosensor for pH-Dependent Cell Labeling.

Here we present a "smart" xenon-129 NMR biosensor that undergoes a peptide conformational change and labels cells in acidic environments. To a cryptophane host molecule with high Xe affinity, we conjugated a 30mer EALA-repeat peptide that is α-helical at pH 5.5 and disordered at pH 7.5. The (129)Xe NMR chemical shift at room temperature was strongly pH-dependent (Δδ = 3.4 ppm): δ = 64.2 ppm at pH 7.5 vs δ = 67.6 ppm at pH 5.5, where Trp(peptide)-cryptophane interactions were evidenced by Trp fluorescence quenching. Using hyper-CEST NMR, we probed peptidocryptophane detection limits at low-picomolar (10(-11) M) concentration, which compares favorably to other NMR pH reporters at 10(-2)-10(-3) M. Finally, in biosensor-HeLa cell solutions, peptide-cell membrane insertion at pH 5.5 generated a 13.4 ppm downfield cryptophane-(129)Xe NMR chemical shift relative to pH 7.5 studies. This highlights new uses for (129)Xe as an ultrasensitive probe of peptide structure and function, along with potential applications for pH-dependent cell labeling in cancer diagnosis and treatment.

Structural Characterization of Micro- and Mesoporous Carbon Materials Using In Situ High Pressure 129Xe NMR Spectroscopy

In situ high pressure 129Xe NMR spectroscopy in combination with volumetric adsorption measurements were used for the textural characterization of different carbon materials with well-defined porosity including microporous carbide-derived carbons, ordered mesoporous carbide-derived carbon, and ordered mesoporous CMK-3. Adsorption/desorption isotherms were measured also by NMR up to relative pressures close to p/p0 = 1 at 237 K. The 129Xe NMR chemical shift of xenon adsorbed in porous carbons is found to be correlated with the pore size in analogy to other materials such as zeolites. In addition, these measurements were performed loading the samples with n-nonane. Nonane molecules preferentially block the micropores. However, 129Xe NMR spectroscopy proves that the nonane also influences the mesopores, thus providing information about the pore system in hierarchically structured materials.

Temperature dependence of the mean size of polyphenyleneoxide microvoids, as studied by Xe sorption and 129Xe NMR chemical shift analyses

Both the Xe sorption isotherms and 129Xe NMR spectra of poly(2,6-dimethyl-1,4-phenylene oxide), PPO, were obtained across a temperature range of –55 °C to +80 °C to investigate the temperature dependence of the gas sorption and the unrelaxed volume of PPO. All of the obtained sorption isotherms were analyzed based on the dual-mode sorption model, and the Langmuir saturation constant, CH′, which corresponds to the unrelaxed volume, was determined by curve fitting. The values of CH′ increased linearly with decreasing temperature, and the obtained temperature was almost identical to the glass transition temperature, Tg, of PPO when the CH′ value was extrapolated to 0. The 129Xe NMR chemical shift of 129Xe in the PPO showed a nonlinear, low-field shift with increasing Xe pressure at temperatures below the Tg. The mean volumes of individual microvoids were determined at each temperature based on the 129Xe NMR chemical shift analysis, assuming a fast exchange of the Xe atoms between the Henry and Langmuir sorption sites. The temperature dependence of the individual microvoid volumes was similar to that of CH′. 129Xe NMR spectra of 129Xe in polyphenyleneoxide, PPO were measured at various temperatures below Tg. From the analysis of 129Xe NMR chemical shifts, the mean volume of individual microvoids in PPO, v could be determined. The temperature when value of v becomes same as a Xe atom, was very close to Tg of PPO. Temperature dependence of individual microvoid’s volume was very similar with that of CH′, which is obtained by dual-mode sorption model from Xe sorption isotherms and is corresponding to the unrelaxed volume of PPO in the glassy state.

Characterization of the microvoids of a tetramethyl polycarbonate/polystyrene blend system using Xe sorption measurements and 129Xe NMR spectroscopy

Xe sorption properties of tetramethyl bisphenol A polycarbonate (TMPC)/polystyrene (PS) blends indicated the reduction of microvoids by blending. From the analysis of 129Xe NMR chemical shifts of the 129Xe in these blends, the mean volume of individual microvoids (v) was calculated. The v values for these blends were smaller than those of predicted by a simple additive rule, as well as the cases of variation of density and Xe sorption properties. This fact indicates that the volume contraction induced by blending for TMPC/PS blends is mainly attributed to contraction volume of individual microvoids.

Does hydrogen bonding to xenon affect its 129Xe NMR chemical shift? Computational study on selected Brønsted acid–xenon complexes

H-bonding-like interactions between Xe and twelve A–H acids is examined by analysis of calculated A–H⋯Xe geometry and the 129Xe shielding. It was shown that δ(129Xe) is proportional to the 129Xe shielding anisotropy in most cases, generally increases with the A–H proton deshielding and depends on the A–H acidity (PA) on two ways: for stronger and weaker acids δ(129Xe) increases and decreases with PA, respectively. The highest contribution to the δ(129Xe) tensor variations comes from its principal components perpendicular to the H⋯Xe bond. These components are also sensitive on side interactions in non-linear dimers.

Simulations of 129Xe NMR chemical shift of atomic xenon dissolved in liquid benzene

The isotropic 129Xe NMR chemical shift of atomic Xe dissolved in liquid benzene was simulated by combining classical molecular dynamics and quantum chemical calculations of 129Xe nuclear magnetic shielding. Snapshots from the molecular dynamics trajectory of xenon atom in a periodic box of benzene molecules were used for the quantum chemical calculations of isotropic 129Xe chemical shift using nonrelativistic density functional theory as well as relativistic Breit–Pauli perturbation corrections. Thus, the correlation and relativistic effects as well as the temperature and dynamics effects could be included in the calculations. Theoretical results are in a very good agreement with the experimental data. The most of the experimentally observed isotropic 129Xe shift was recovered in the nonrelativistic dynamical region, while the relativistic effects explain of about 8% of the total 129Xe chemical shift.

Shorter Synthesis of Trifunctionalized Cryptophane-A Derivatives

Efficient syntheses of trisubstituted cryptophane-A derivatives that are versatile host molecules for many applications are reported. Trihydroxy cryptophane was synthesized in six or seven steps with yields as high as 9.5%. By a different route, trihydroxy cryptophane modified with three propargyl, allyl, or benzyl protecting groups was synthesized with yields of 4.1-5.8% in just six steps. Hyperpolarized (129)Xe NMR chemical shifts of 57-65 ppm were measured for these trisubstituted cryptophanes.

A Water-Soluble Xe@cryptophane-111 Complex Exhibits Very High Thermodynamic Stability and a Peculiar 129Xe NMR Chemical Shift

The known xenon-binding (±)-cryptophane-111 (1) has been functionalized with six [(η(5)-C(5)Me(5))Ru(II)](+) ([Cp*Ru](+)) moieties to give, in 89% yield, the first water-soluble cryptophane-111 derivative, namely [(Cp*Ru)(6)1]Cl(6) ([2]Cl(6)). [2]Cl(6) exhibits a very high affinity for xenon in water, with a binding constant of 2.9(2) × 10(4) M(-1) as measured by hyperpolarized (129)Xe NMR spectroscopy. The (129)Xe NMR chemical shift of the aqueous Xe@[2](6+) species (308 ppm) resonates over 275 ppm downfield of the parent Xe@1 species in (CDCl(2))(2) and greatly broadens the practical (129)Xe NMR chemical shift range made available by xenon-binding molecular hosts. Single crystal structures of [2][CF(3)SO(3)](6)·xsolvent and 0.75H(2)O@1·2CHCl(3) reveal the ability of the cryptophane-111 core to adapt its conformation to guests.

Analysis of the Temperature and Pressure Dependence of the 129Xe NMR Chemical Shift and Signal Intensity for the Derivation of Basic Parameters of Adsorption as Applied to Zeolite ZSM-5

Temperature and pressure dependences of the 129Xe NMR chemical shift and the signal intensity have been investigated using ZSM-5 as an adsorbent under routine conditions without using any high-pressure or especially high-temperature facilities. The use of a rigorously shielded system and a calibration sample for the signal intensity was found to be valuable to obtain reliable data about the chemical shift and the signal intensity. The 129Xe NMR data obtained between 0.05 and 1.5 atm and from 24 to 80 degrees C were analyzed based on the Dubinin-Radushkevich equation as well as the Langmuir type equation. In both analyses, chemical shift data succeeded only partially in providing the profile of adsorption, such as energetic aspects, surface area, saturated amount of Xe adsorption and specific parameters of 129Xe chemical shift. It was shown that the reliable total analysis was achieved when the chemical shift data were used together with the intensity data. Such an analysis of the chemical shift data, aided by the intensity data, will be useful in performing nano-material analysis on 129Xe NMR without invoking the traditional methodology of gravimetric or volumetric adsorption experiments.

Cross-Link Density of a Dispersed Rubber Measured by 129Xe Chemical Shift

129Xe NMR chemical shifts of adsorbed xenon (natural isotopic abundance) were used to probe the free volume in a cross-linked rubber, polybutadiene (PB), alone and occluded within high impact polystyrene (HIPS). Shift dependency on cross-link density, or Nm (average number of monomer units between chemical cross-links) determined by the classical solvent swelling method, was detailed for high-cis-1,4-PB. A decrease in Nm from 262 to 4 caused the shift to increase 4 ppm. A curve inflection, evident at 218 ppm (and Nm = 30), corresponded to a free volume with an average spherical diameter of 0.49 nm using the empirical (shift-pore size) relation known for zeolites. This diameter is essentially equal to that of the PB chain (0.48 nm) at its Tg (glass transition temperature). Tg plotted against Nm showed the same inflection (at Nm = 25), corroborating a regime with more severe interchain contacts when the free volume diameter is inferior to the chain diameter. The empirical relation between 129Xe shift and Nm observed for pure PB was used to estimate the cross-link density of PB dispersed in HIPS as a function of cure time. Cross-linkage was greatly slowed after 8 h of curing, when Nm estimated by NMR spectroscopy was 10.

Evaluation of nanometer-scale droplets in a ternary o/w microemulsion using SAXS and 129Xe NMR

This study revealed a linear correlation between the nanometer-scale oil droplet sizes estimated using small angle X-ray scatterings (SAXS) and the 129Xe NMR chemical shift in an oil-in-water ternary microemulsion system comprising pentaethylene glycol mono- n-dodecyl ether, n-decane, and deuterium oxide. The absolute values of the droplet size estimated using 129Xe NMR show good agreement with those using SAXS. We also found that the results are consistent with a reported relation derived using small angle neutron scattering. The results suggest the validity of 129Xe NMR chemical shifts for investigation of colloidal systems to evaluate their internal structures’ characteristic sizes.

Protein Tyrosine Phosphatase Oligomerization Studied by a Combination of 15N NMR Relaxation and 129Xe NMR. Effect of Buffer Containing Arginine and Glutamic Acid

15N NMR relaxation and 129Xe NMR chemical shift measurements offer complementary information to study weak protein-protein interactions. They have been applied to study the oligomerization equilibrium of a low-molecular-weight protein tyrosine phosphatase in the presence of 50 mM arginine and 50 mM glutamic acid. These experimental conditions are shown to enhance specific protein-protein interactions while decreasing nonspecific aggregation. In addition, 129Xe NMR chemical shifts become selective reporters of one particular oligomer in the presence of arginine and glutamic acid, indicating that a specific Xe binding site is created in the oligomerization process. It is suggested that the multiple effects of arginine and glutamic acid are related to their effective excluded volume that favors specific protein association and the destabilization of partially unfolded forms that preferentially interact with xenon and are responsible for nonspecific protein aggregation.

129Xe NMR study of xenon in iso-reticular metal–organic frameworks

Hyperpolarized 129Xe NMR spectroscopy is used to investigate the interaction of xenon with four different zinc metal–organic frameworks, IRMOF-1, -7, -8, and -10. Each of the frameworks has a cubic cage of varying size, depending on the organic linker molecule. The 129Xe NMR chemical shifts are influenced by both the cage dimensions and the distribution of xenon within the framework. NMR spectra acquired at low temperature suggest that high xenon loadings can be achieved using the continuous-flow hyperpolarized 129Xe NMR experiment. Information about the adsorption energy is inferred from the behaviour of the xenon chemical shifts as a function of temperature and analyzed for IRMOF-10. The rate at which xenon diffuses through the IRMOF is probed using a signal recovery NMR experiment.

Grand Canonical Monte Carlo Simulations of the 129Xe NMR Line Shapes of Xenon Adsorbed in (±)-[Co(en)3]Cl3

The 129Xe NMR line shapes of xenon adsorbed in the nanochannels of the (+/-)-[Co(en)3]Cl3 ionic crystal have been calculated by grand canonical Monte Carlo (GCMC) simulations. The results of our GCMC simulations illustrate their utility in predicting 129Xe NMR chemical shifts in systems containing a transition metal. In particular, the nanochannels of (+/-)-[Co(en)3]Cl3 provide a simple, yet interesting, model system that serves as a building block toward understanding xenon chemical shifts in more complex porous materials containing transition metals. Using only the Xe-C and Xe-H potentials and shielding response functions derived from the Xe@CH4 van der Waals complex to model the interior of the channel, the GCMC simulations correctly predict the 129Xe NMR line shapes observed experimentally (Ueda, T.; Eguchi, T.; Nakamura, N.; Wasylishen, R. E. J. Phys. Chem. B 2003, 107, 180-185). At low xenon loading, the simulated 129Xe NMR line shape is axially symmetric with chemical-shift tensor components delta(parallel) = 379 ppm and delta(perpendicular) = 274 ppm. Although the simulated isotropic chemical shift, delta(iso) = 309 ppm, is overestimated, the anisotropy of the chemical-shift tensor is correctly predicted. The simulations provide an explanation for the observed trend in the 129Xe NMR line shapes as a function of the overhead xenon pressure: delta(perpendicular) increased from 274 to 292 ppm, while delta(parallel) changed by only 3 ppm over the entire xenon loading range. The overestimation of the isotropic chemical shifts is explained based upon the results of quantum mechanical 129Xe shielding calculations of xenon interacting with an isolated (+/-)-[Co(en)3]Cl3 molecule. The xenon chemical shift is shown to be reduced by about 12% going from the Xe@[Co(en)3]Cl3 van der Waals complex to the Xe@C2H6 fragment.