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Xenon in Chemistry and Medicine

Given paper aims to reveal xenon’s properties and its application. From the chemist’s point of view, xenon is the strangest gas among the rest of inert gases. Xenon first underwent the chemical reaction forming a stable compound. Therefore, this gas made the term noble gases irrelevant. Today, xenon is widely used for developing treatment methods of various diseases in medicine, namely xenon therapy. It is also used for anesthesia owing to a number of its advantages. This gas exists in small quantities in the air and is harmless and non-allergenic. It can interact with many drugs making its application possible at any age.

In 1785, English explorer Cavendish, studying the composition of the atmosphere with the use of spark discharge, found that 1/120 of the air is neither nitrogen nor oxygen (De Kumar 603). In 1894, British scientists Ramsay and Rayleigh repeated Cavendish’s experiment proving by spectroscopic analysis the existence of residual argon gas (De Kumar 603). At that time, a group of inert (noble) gas elements of the periodic system was discovered.


Noble gases are unusual chemical elements that differ from all others because their atoms have complete outer electron shell (Wicander and Monroe 21). In addition, these gases do not form natural compounds since they exist in small amounts in nature. The difficulty of detecting noble gases lies in the fact that 1m3 of air has only 0.08 ml of xenon (De Kumar 603). Discovery of the noble gases is a critical step in the development of chemistry that gave internal logic to the periodic system, the essence of which is to end the chemical element with complete external electronic level. This fact was the key moment in the creation of valence electron theory by Lewis (Purdue University).

According to this theory, all atoms of the periodic system (besides the atoms of transition elements) are structured in their stable connections. Atoms of noble gases, except helium, have eight electrons in the outer shell, which occupy four orbitals (one S orbital and three P orbitals). These eight electrons are called an octet (Wicander and Monroe 21). Status of a molecule is considered the most stable when each atom attains completed octet. This explains the fact that the noble gas atoms are characterized by high values of energy ionization and negative values of the electron affinity. Currently, argon, krypton and xenon are produced through fractional distillation of liquid air in the deep-cooling (Shakhashiri). For a long time scientists thought the noble gases were chemically dead. Although over a hundred years have passed since their discovery, the study of these compounds is only at the initial stage of its development. Helium and neon are so inert that their compounds have not been obtained yet (Shakhashiri). However, today humanity can describe and analyze the chemical properties of the noble gases.

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Xenon is a colorless inert gas having nine isotopes, two of which, Xe127 and Xe133 in particular, are used in the clinical physiology for the study of the respiratory function of lungs and blood (Brant and Helms 1263). External electronic level of xenon is filled with an octet of electrons (5s2 and 5p6) (Chandra 311). Therefore, like all noble gases, at room temperature xenon is composed of monatomic molecules. Melting and boiling points of xenon are 111,85 °C and - 108,12 °C respectively. Xenon is poorly soluble in water and thus, it better dissolves in organic solvents. It does not react with acids or alkalis and is capable of dissolving in organic solvents such as phenol or hydroquinone 4Хе·6Н5ОН (Chandra 306). Claasen, Selig and Malm discovered the first compound of this noble gas - XeF4 (Chandra 306). Xenon is able to form fluorides due to the higher electronegativity of fluorine in comparison with xenon. Xenon is capable of chlorinating in the temperature range from -230 °C to room temperature under an electric discharge: Xe + Cl2 = XeCl2 (Chandra 307). Reactive xenon hexafluoride reacts with alkalis and silica fluoride (Chandra 307). Interaction with the hot water is one of the most dangerous chemical reactions of the noble gases, because it is accompanied by the formation of an explosive xenon trioxide:

XeF6 + 3 H2O = XeO3 + 6 HF

XeO3 = Xe + 1,5 О2 + 402 kJ / mol

XeO3 and XeO4 are volatile oxides that exhibit acid properties, partly in response to the water and completely with alkalis:

XeO3 + 2 H2O - N2XeO4
2 XeO3 + 3 NaOH (cold) > NaHXeO4 + Na2XeO4 + H2O
XeO4 + 2 H2O - H4XeO6
XeO4 + 2 NaOH > Na2H2XeO6 

All of these compounds are potent oxidants that can be easily decomposed. Currently, chemists try to obtain a compound of xenon with other elements such as carbon and nitrogen - (NO)+2XeF8  (Zuckerman and Hagen 264). Yet, the question of their practical use has not been raised despite the huge interest in the structure and processes of the formation of chemical bonds in molecules and synthesized substances. Chemical inertness of noble gases encourages the search of other representatives of their type. It is noteworthy to discuss the use of xenon as an anesthetic. In 1946, narcotic properties of this gas were predicted and later confirmed (Colloc’h et al.). First application of xenon in clinic anesthesia dates back to 1951. Today, anesthesiology uses only two inhaled anesthetic gases, namely nitrous oxide (N2O) and xenon, as well as liquid gases including halothane, isoflurane, enflurane, sevoflurane and desflurane (Colloc’h et al.). Despite the fact that over a half century passed since the first use of ether anesthesia, there is still no unified theory of anesthesia.

Currently, there are four theories of inhalation anesthesia such as coagulation, lipoid, adsorption and surface tension theory. However, none of them is universal. Ability of the noble gases, including xenon, to form crystalline hydrates (clathrates) established interesting interpretation of action mechanism of chemically inert anesthetic agents such as halothane and xenon (Yu et al.). According to this mechanism, formed micro crystals of xenon clathrate (Xe•5.75 H2O) are able to break the water structure of intercellular or intracellular fluid and penetrate the cell membranes. They are also able to inhibit the transport of cations, prevent depolarization of the postsynaptic membrane and block the action potential (Yu et al.). However, this theory has not found full experimental confirmation. Results of recent studies have shown that besides powerful inhibition of the cerebral cortex, anesthetics affect reticular substance of the brain (Møller 325). This fact served as a prerequisite for the creation of a reticular anesthesia theory. The question about which of the mechanisms implemented with the participation of xenon is not answered yet.

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However, authors of basic clinical and experimental studies of xenon anesthesia pointed to the absence of its damaging effect on the internal organs of experimental animals after both single and repeated inhalation exposures. Extended clinical tests indicated that xenon-oxygen mixture provides the required level of anesthetic protection without causing a negative effect on the cardiovascular system, the morphology and biochemistry of blood (Abramo et al.). In addition, allergenic properties of xenon have not been detected.

From the standpoint of xenon’s chemical activity, analysis of the literature data shows dual phenomenology. This refers to an anesthetic effect and the absence of significant biochemical changes. The interest in the search of possible explanatory reasons of this phenomenon has led to extensive research recently. Instead of studying the general problems of modern clinical anesthesiology as well as questions of daily anesthetic practice, research shifted its emphasis to the search of information about possible mechanisms of the biological activity of xenon.

There is evidence that the antinociceptive effect of xenon results from its direct effect on the neurons of the posterior horn of the spinal cord (Georgiev et al.). Other authors showed that xenon anesthesia was accompanied by an increased cyclic guanosine monophosphate concentration in the spinal cord in the trunk portion and paleocortex (Toda et al.). Fluctuations in the concentration of cyclic nucleotides promote occurrence of changes in neurons, which modulate cholinergic transmission. It is also known that an increase of cyclic guanosine monophosphate content accompanies reduction in the concentration of cyclic adenosine monophosphate including brain cells in the cultures. In turn, the decrease in the concentration of cyclic adenosine monophosphate usually results from adenylate cyclase inhibition, which is activated by prostaglandins of E group (Toda et al.). Thus, there is a vision that excessive suppression activity called prostaglandin cascade may take place in the mechanism of xenon anesthesia inhibiting the formation of pain transduction level. In this case, prostaglandin cascade is one of the main mediators of pain (Ricciotti and FitzGerald).

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In recent years, the results of numerous studies have allowed to create the NMDA-receptor theory (N-methyl-D-aspartate) of xenon anesthesia. NMDA receptors are among the glutamine ionotropic receptors, which have a special role in the regulation of neuronal excitability, synaptic plasticity and pathogenesis of neuro-degeneration. These receptors can be included in the etiology of chronic pain (Hummel et al.). The highest density of NMDA receptors is found in the hippocampus, cerebral cortex, amygdale and striatum (Hummel et al.). These receptors build receptor-ion based complex consisting of several subunits of glycoprotein lipids. Xenon attenuates neurological and neurocognitive dysfunction. Unlike N2O, xenon is devoid of neurotoxicity and adverse effects on hemodynamics. Yet, studies of Weigt et al., have shown that xenon does not act as a classical channel blocker of NMDA receptors. Experiments on mice demonstrated that xenon-oxygen mixture (80:20) favorably influence the morphology and state of organs and tissues in a drunken state as well as in cases of hypoxic ischemia, acute paralysis and other (Dingleu et al.).

Xenon is one of the noble gases known for its chemical inertness. Its unique physical and chemical properties are widely used in medicine. It opens up new horizons in biomedical practice as it combines low toxicity with the ability to dissolve in body fluids and cell membranes as well as exercise effects on the metabolic and cellular processes. Xenon gas is colorless, tasteless, odorless and nontoxic, and it does not cause chemical effects. It has unique biochemical property of anesthesia. The ability to inhibit NMDA receptors is among the possible mechanisms of antinociceptive effect of xenon, which is proved by numerous model experiments. Clinical investigations of xenon point to its several advantages as an anesthetic including cardio protective, neuro protective and radio protective properties. Yet, there are still issues to be discovered and solved before the safe usage of xenon in medicine. However, the introduction of xenon anesthesia in anesthetic practice is a new direction in the field of medicine as well as in the field of bioorganic chemistry.

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