Xenon NMR: chemical shifts of a general anesthetic in common solvents, proteins, and membranes.

Abstract

The rare gas xenon contains two NMR-sensitive isotopes in high natural abundance. The nuclide '"Xe has a spin of 'h; '31Xe is quadrupolar with a spin of 3/2. The complementary NMR characteristics ofthese nuclei provide a unique opportunity for probing their environment. The method is widely applicable because xenon interacts with a useful range of condensed phases including pure liquids, protein solutions, and suspensions of lipid and biological membranes. Although xenon is chemically inert, it does interact with living systems; it is an effective general anesthetic. We have found that the range of chemical shifts of '"Xe dissolved in common solvents is ca. 200 ppm, which is 30 times larger than that found for 13C in methane dissolved in various solvents. Resonances were also observed for 131Xe in some systems; they were broader and exhibited much greater relaxation rates than did '29Xe. The use of '29Xe NMR as a probe of biological systems was investigated. Spectra were obtained from solutions of myoglobin, from suspensions of various lipid bilayers, and from suspensions of the membranes of erythrocytes and of the acetylcholine receptor-rich membranes of Torpedo californica These systems exhibited a smaller range ofchemical shifts. In most cases there was evidence of a fast exchange of xenon between the aqueous and organic environments, but the exchange was slow in suspensions of dimyristoyl lecithin vesicles.Xenon NMR spectroscopy is a potential probe of the structural and dynamic aspects ofthe molecular environment ofthe xenon atom in physical and biological media. Natural xenon contains 26% '29Xe which has spin I = 1/2 and 21% 131Xe which is a quadrupolar nucleus and has spin I = 3/2. The NMR sensitivity of '29Xe is relatively large and the solubility of xenon in most liquids is high for an apolar gas-e.g., from 4.3 mM in water to 166 mM in isooctane at 1 atm and 273 K-so the NMR spectra ofboth isotopes can be observed with commercial multinuclear spectrometers. The chemical shift of the xenon atom is especially reflective of its environment due to its large, polarizable, electron cloud. In xenon compounds, shifts up to 4000 ppm have been observed (1). In the free xenon atom, the effects of the medium can produce sizable shifts. Such shifts have been observed in pure liquid and gaseous xenon as well as in gas mixtures of xenon with a second component (1). However this effect had not been studied in condensed phases. We have observed solvent-dependent shifts over a range of ca. 200 ppm, a range that is much larger than the solvent shifts of 13C and 19F (2, 3).Xenon interacts with many biological systems including myoglobin (4) and hemoglobin (5). It is also soluble in lipid bilayers: membrane/gas partition coefficients vary from 0.4 (at 20°C) in erythrocytes (6) to 1.3 (at 25°C) in egg lecithin (unpublished data). Its most striking pharmacological property is its ability to induce general anesthesia; its efficacy is comparable to that of nitrous oxide (7). The physicochemical mechanism of anestheti...

High resolution spectroscopy and chemical shift imaging of hyperpolarized 129Xe dissolved in the human brain in vivo at 1.5 tesla

“…These earlier studies suggested the following peak assignments: 187.2 ppm, muscle 19, 20, 21; 192.7 ppm, white matter (and soft‐tissue in this study) 18, 19, 20, 21; 195.6 ppm, gray matter 18, 19, 20, 21; 199.6 ppm, aqueous solution (cerebrospinal fluid, plasma, and interstitial fluid in this study) 10, 11, 24, 25, 26 and fat/lipid tissue outside the brain 19, 20; and 217.2 ppm, red blood cells 4, 10, 24, 26.…”

Development of a Functionalized Xenon Biosensor

“…[35][36][37] Recently, extensive reviews regarding the history and development of hyperpolarized xenon NMR have been published. 38,39 Biological systems studied with 129 Xe NMR include globular proteins such as myoglobin and hemoglobin, [40][41][42][43][44][45][46] membrane associated peptides such as gramicidin, 47 and lipid membranes themselves. 48 While xenon shows appreciable binding to many proteins, as evidenced by its use in making heavy atom derivatives of protein crystals for x-ray crystallography, 49 In spite of the favorable attributes of xenon interacting with proteins in solution, high-sensitivity molecular sensing is not compatible with the fast-exchange characteristic of xenon-protein interactions.…”

Simultaneous magnetic resonance imaging of ventilation distribution and gas uptake in the human lung using hyperpolarized xenon-129

“…In particular, xenon's relatively high solubility in biological tissues (2), along with its exquisite sensitivity to its environment that results in an enormous range of chemical shifts upon solution (3), make hyperpolarized Xe129 particularly attractive for exploring certain characteristics of lung function, such as gas exchange and uptake (4,5), not accessible with the use of hyperpolarized He3. Upon inhalation, Xe129 gives rise to multiple MRI spectral peaks in the lung (6)(7)(8)(9), each associated with a physically different compartment.…”