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Review

Noble Gases in Medicine: Current Status and Future Prospects

by
David A. Winkler
1,2,3
1
Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Kingsbury Drive, Bundoora 3086, Australia
2
Monash Institute of Pharmaceutical Sciences, Monash University, 392 Royal Parade, Parkville 3052, Australia
3
School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
Oxygen 2024, 4(4), 421-431; https://doi.org/10.3390/oxygen4040026
Submission received: 31 October 2024 / Revised: 10 November 2024 / Accepted: 13 November 2024 / Published: 16 November 2024
(This article belongs to the Special Issue Interaction of Oxygen and Other Gases with Haem Containing Proteins)
Versions Notes

Abstract

:
Noble gases are a valuable but overlooked source of effective and safe therapeutics. Being monoatomic and chemically inert, they nonetheless have a surprisingly wide range of biochemical and medically valuable properties. This mini review briefly summarizes these properties for the most widely used noble gases and focuses and research gaps and missed opportunities for wider use of these intriguing ‘atomic’ drugs. The main research gaps and opportunities lie firstly in the application of advanced computational modelling methods for noble gases and recent developments in accurate predictions of protein structures from sequence (AlphaFold), and secondly in the use of very efficient and selective drug delivery technologies to improve the solubility, efficacy, and delivery of noble gases to key targets, especially for the lighter, poorly soluble gases.

1. Introduction

Noble gases, as all chemists well know, are very chemically inert. They require extreme reaction conditions to form compounds due to their full outer shell of electrons, although their chemistries are undergoing a slow renaissance (see recent review by Mazej [1]). Paradoxically, they exhibit a diverse and potentially useful range of biochemical and medical properties, so have found increasingly significant roles in medicine. Some of the noble gases (helium, neon, argon, krypton, xenon, and radon) exhibit anesthetic, neuroprotective, medical imaging, respiratory therapy, and anticancer properties. Given that they are atoms with a very limited set of physicochemical properties, it has been puzzling how they interact with biological entities to generate manifold in vivo responses. Unlike small organic drug molecules, they cannot assume different shapes that can fit to into protein binding sites, do not have hydrogen bonding capabilities, and have no charge properties that can participate in salt bridges. Their principal physicochemical properties are confined to volume, polarizability, and lipophilicity (affinity for non-polar, or ‘fatty’ environments), see Table 1. Lipophilicity is correlated with aqueous solubility, with the lighter noble gases being much less soluble. Structural biology and computational studies have been integral in understanding how noble gases interact non-specifically and specifically with biochemical and medical targets to generate the wide range of biological responses that have been observed to date. Comprehensive reviews of the biomedical properties of most noble gases have been published recently [2,3]. Consequently, this mini review will provide only a brief summary of the more mainstream medical applications of noble gases. Its major focus is on new therapeutic opportunities, delivery systems for noble gases, and the impact of computational methods on elucidating the biochemical properties of these gases and discovery of new biomedical targets for these rather unique ‘atomic drugs’. The opportunities identified here for noble gases are, of course, also applicable to the other therapeutic gases: CO, NO, N2O, H2S, SO2, H2, CO2, and O2.
To date, the biomedical focus has been primarily on xenon, argon, helium, and krypton. This is partly historical, e.g., use of helium for deep sea diving, and partly driven by empirical or directed studies of medical properties modulated by opportunity, cost, aqueous and blood solubility, and efficacy. Clearly, the medical applications of radon are quite limited due to its radioactive nature [7]. Interestingly, a recent dissertation alluded to the potential of radon to bind to similar target proteins as xenon [8].

2. Xenon: The Multifunctional Noble Gas

Xenon, the heaviest non-radioactive noble gas, is the most studied in medicine due to its wide range of effects that include anesthesia, neuroprotection, and medical imaging.

2.1. Xenon as an Anaesthetic

Xenon’s use in anesthesia is well-established as it has several advantages over traditional anesthetics like halogenated agents. It has a rapid induction and recovery time, minimal cardiovascular effects, and lack of organ toxicity. It is highly effective, especially for high-risk patients undergoing major surgeries [9,10]. Xenon acts primarily by inhibiting NMDA (N-methyl-D-aspartate) receptors in the central nervous system, which reduces excitatory neurotransmission and produces anesthesia without the depressive effects seen with other agents [11,12,13].
Direct actions at other glutamate receptors, potassium channels, and other targets have also been reported [14]. Conspicuously, unlike most general anesthetics, it does not enhance the activity of inhibitory GABAA (γ-aminobutyric acid type-A) receptors [9]. Computational studies have shown that it can also alter the properties of lipid biolayers, e.g., cell membranes, in a similar manner to other general anesthetics [15].
In clinical trials, xenon anesthesia demonstrated excellent cardiovascular stability during coronary artery bypass surgery compared to agents like sevoflurane, which are known for their cardiodepressive effects [16]. Its lack of interaction with the hepatic or renal systems adds to its safety profile [16]. However, the high cost of xenon has limited its widespread adoption in routine clinical practice [17].
There is considerable scope for better delivery systems for xenon to be developed that would require far less gas and enable selective and triggered release in the relevant body compartments (see later discussion on noble gas delivery systems) [2].

2.2. Xenon in Neuroprotection

With the increasing use of organ transplants and ageing populations suffering higher levels of ischemic events, xenon’s neuroprotective properties have been of particular interest [3]. Xenon has shown promising outcomes in the treatment of ischemic cardiac events and brain injuries like stroke and neonatal hypoxia. As with anesthesia, xenon’s ability to inhibit NMDA receptors, a critical pathway in excitotoxicity, helps to reduce neuronal damage during ischemic events [9].
Xenon also inhibits the serine protease, tissue plasminogen activator (tPA). Intra-ischemic administration reduces tPA-induced thrombolysis and subsequent lowers ischemic brain damage, dose-dependently. When administered postischemically, xenon essentially suppresses ischemic brain damage and tPA-induced brain hemorrhages and disruption of the blood–brain barrier. Some authors have suggested xenon be a gold standard for treating acute ischemic stroke, if given after tPA-induced reperfusion, due to its unique neuroprotective and antiproteolytic (anti-hemorrhage) properties [18]. Xenon has also been shown to preserve mitochondrial function, crucial for cell survival during hypoxic conditions [19].
In neonatal medicine, xenon has exhibited improved outcomes in infants with hypoxic-ischemic encephalopathy (HIE), especially when combined with therapeutic hypothermia [20,21]. It significantly reduces brain damage and improves neurodevelopmental outcomes [21,22,23]. Similarly, studies in adult patients who suffered cardiac arrest and ischemic stroke have demonstrated improved neurological recovery when xenon was administered as part of post-resuscitation care [24,25].

2.3. Xenon in Imaging

Xenon is also a useful contrast agent in medical imaging studies, particularly those using hyperpolarized xenon-129 (129Xe) in MRI scans. Hyperpolarization and inhalation are required as their nuclear density is too low to yield a useful signal under normal conditions. Xenon scans have reduced background noise and increased contrast because the gas is not normally present in biological tissues [26]. It is used to visualize pulmonary function, blood flow, and brain perfusion. In lung imaging, hyperpolarized 129Xe MRI provides a non-invasive method for assessing ventilation defects, making it useful in diseases like asthma, COPD, and interstitial lung diseases [27]. Xenon’s solubility in blood and tissues (compared to the lighter noble gases, see Table 1) also allows dynamic imaging of organ perfusion, especially in the brain, kidney, and heart [28].

3. Argon: The Emerging Neuroprotectant

Argon constitutes around 1% of the atmosphere. It is a cost-effective and useful noble gas with promising neuroprotective properties. However, unlike xenon, argon is not useful as an anesthetic (its low solubility means that hyperbaric conditions are required for it to exhibit measurable anesthetic properties) [2,29,30]. However, soluble argon has demonstrated efficacy in reducing neuronal apoptosis and inflammation following ischemic injuries [31].

Mechanism of Action

Argon’s neuroprotective mechanism is multifaceted. While it does not act directly on NMDA receptors like xenon, it modulates intracellular signaling pathways related to apoptosis and inflammation. Studies have shown that argon upregulates anti-apoptotic proteins like B-cell leukemia/lymphoma 2 (Bcl-2) and reduces pro-apoptotic factors such as Bcl-2 associated X-protein (Bax), thereby preventing cell death after ischemic events. Argon reduces anti-oxidative stress, inflammation and has anti-apoptotic cytoprotective effects. These mainly involve the Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and, as stated, Bcl-2. This makes argon a potential treatment option for ischemic strokes, traumatic brain injury, spinal cord injuries, and retinal ischemia [32,33,34].

4. Helium: Low Density and Respiratory Support

Helium, the lightest noble gas, has been used in respiratory medicine for decades. Its low density reduces airway resistance and helps to improve gas exchange, making it a valuable tool in treating various pulmonary diseases such as chronic obstructive pulmonary disease and bronchiolitis [35].

4.1. Heliox Therapy

Heliox, a mixture of helium and oxygen, has been employed in critical care settings to treat patients with severe airway obstructions, such as those caused by asthma, bronchiolitis, or upper airway tumors [36]. Helium’s low density reduces the work of breathing by decreasing airway resistance, allowing for easier airflow and more efficient oxygen delivery [26]. In emergency settings, heliox therapy has been shown to improve ventilation and reduce the need for mechanical ventilation [27]. Heliox treatment of COVID-related respiratory infections and pneumonia have also been evaluated in multiple studies [35].

4.2. Helium’s Role in Imaging

In addition to its use in respiratory therapy, helium-3 (3He) has been studied as a hyperpolarized gas for MRI, particularly for imaging lung function. 3He MRI allows high-resolution visualization of ventilation in the lungs and can detect early changes in lung architecture caused by diseases like emphysema and cystic fibrosis [37]. However, the rarity and exorbitant price of 3He, and its low solubility, means that dissolved phase imaging using 129Xe is more practical, prompting a shift away from 3He in recent years [38].

5. Krypton: The Underexplored Noble Gas

Krypton is more abundant and less expensive than xenon but is less researched than xenon or argon. It has shown potential in medical applications, particularly in anesthesia and imaging. Paradoxically, krypton shows no effect on hypoxic-ischemic brain injury and has not been shown to exhibit any other beneficial neuro- or tissue-protective properties under normal pressures [39]. Further research may provide an explanation for this dearth of properties or may reveal under which circumstances these properties emerge.

5.1. Krypton in Anaesthesia

Like xenon, krypton has been evaluated for its anesthetic properties. It has a lower anesthetic potency than xenon but can produce anesthesia under milder hyperbaric conditions of 4.5 atm (argon requires 15 atm) [40]. It may also be neuroprotective at these pressures. However, its higher minimum alveolar concentration makes it impractical as a general anesthetic. As discussed below, improved delivery systems may expand the use of krypton in anesthesia. Studies have suggested that krypton acts on the same molecular targets as xenon, including NMDA and GABA receptors [31].

5.2. Krypton in Medical Imaging

Krypton has a long history of use in medical imaging, particularly in lung scintigraphy. Krypton-81m (81mKr) is a short-lived radioactive isotope used in ventilation-perfusion (V/Q) scans to assess lung function and detect pulmonary embolism. 81mKr is inhaled, and its distribution in the lungs is imaged using tomographic SPECT V/Q imaging, providing clinicians with detailed information about ventilation defects [41]. This made krypton a useful diagnostic tool for patients with respiratory conditions.

6. Computational Studies on Noble Gases: Predicting Biochemical Targets

Advances in computational modelling have significantly enhanced our understanding of how noble gases interact with biological systems. Computational studies use techniques like molecular dynamics (MD) simulations, quantum mechanical calculations, and protein-ligand docking to predict the biochemical and medical targets of noble gases. A recent study explored how the noble gases interact with the ~60,000 proteins in the structural proteome (the proteins that have experimental 3D structures obtained by X-ray crystallography, cryo-electron microscopy, or NMR) using a robust computational docking method (AutoDock) [42].
Recently, studies by Hancock et al. used Xe to identify an alternative gas transport mode in globins, which they have denoted as “xenon pockets” [43]. They proposed that inert gases may likewise modulate many proteins that have similar cavities, possibly via direct (ligand competitive) or allosteric interactions with proteins. This proposal is consistent with the results of the large pan-protein computational study described above. These results helped to elucidate the mechanisms by which noble gases interact with proteins generally, how they modulate specific, known protein targets such as the NMDA receptor, and validated computational docking methods for reliably predicting the binding sites and strengths of the noble gases [44]. Additionally, some noble gas-specific studies are summarized below.

6.1. Computational Models of Xenon Binding to Haemoproteins and Other Targets

Noble gases, notably Xe, have been valuable for mapping the properties of hemoproteins such as hemoglobin, myoglobin, and neuroglobin [45]. The first computational study of noble gas interactions with hemoproteins was reported by Tilton and coworkers in 1986 [46]. They determined physical and chemical characteristics of xenon binding sites in myoglobin using X-ray crystallography and computational surface analysis. Subsequently, molecular dynamics simulations have calculated the trajectories of xenon entering the binding site of these important oxygen-transport proteins. For example, Cohen et al. used implicit ligand sampling to generate a three-dimensional map of the favorable binding regions and gas migration pathways inside myoglobin [47,48]. They validated their computational binding site results with X-ray structures of proteins with xenon atoms bound to them. The calculated trajectories of Xe in the protein were consistent with the known oxygen channel from the protein surface to heme and was further validated by a picosecond-resolution X-ray crystallography movie of CO migration [49,50].
Xenon’s interaction with NMDA and GABA receptors has been extensively modelled using computational tools. Quantum chemical, molecular dynamics simulations and mathematical models have revealed how xenon binds to NMDA receptor sites, blocking excitatory neurotransmission and producing neuroprotection [51,52,53].

6.2. Argon and Its Molecular Targets

Computational studies of argon have focused on its neuroprotective effects, though less is known about its specific molecular targets compared to xenon. Recent models suggest that argon modulates cellular pathways involved in apoptosis, particularly by stabilizing mitochondrial membranes and inhibiting the release of pro-apoptotic factors [39]. In an attempt to better understand argon’s mechanism of action, Hammami et al. mined the massive noble gas reverse docking database referenced above to identify the potentially relevant binding sites within protein families [54]. They reported for structurally aligned proteins, the shape, localization, hydrophobicity, and binding energies of conserved binding sites. They applied the method to two protein families where crystallography has identified Ar binding sites. The most hydrophobic sites and/or those with the best binding energy corresponded to the crystallographic Ar gas binding sites. The predicted Ar binding sites that have potential pharmacological interest will be validated by further in vitro studies.

6.3. Krypton and Computational Approaches

There are very few published studies on the interaction of krypton with protein targets. Melnikov and coworkers reported X-ray crystallography studies showing that most krypton (and argon) binding sites were on the outer hydrophobic surface of membrane proteins (two proton pumps and a sodium light-driven ion pump in their study). Supplementary molecular dynamics (MD) simulations predicted even larger numbers of noble gas binding positions on protein surfaces within the bilayer [55].
As described above, Winkler et al. reported the computationally predicted binding affinities and binding sites of all non-radioactive noble gases in almost every protein with an experimental structure. Many proteins did not bind the noble gases, but productive sites on other proteins encompassed a combination of size and lipophilicity. These binding data were calculated for krypton in this study [42]. Validation studies showed that the computational docking methods used recapitulated the binding sites of all crystallographic krypton atoms within one Kr vdW diameter of an experimentally determined binding site [44].

7. Safety and Ethical Considerations

The noble gases do not have teratogenic, mutagenic, carcinogenic, or allergenic properties due to their chemical inertness, and do not adversely affect respiratory function. The gases are non-toxic and environmentally benign (as discussed below), but some are expensive due to rarity and the complex process required to isolate it from the atmosphere. Argon and helium are more abundant and less expensive but have lower solubilities that limit their clinical use to specific therapeutic applications. Krypton, though cheaper than xenon, is still more expensive than argon and helium, and its medical use is largely limited to imaging and specialized research contexts. As described above, most noble gases, under normal or hyperbaric conditions, have benefits in terms of fast induction and washout and potentially favorable synergistic polypharmacy effects on sedation, neuroprotection, analgesia, and other CNS actions.

8. Emerging Applications, Research Gaps, and Future Directions

The future of noble gases in medicine is likely to be shaped by the development of more cost-effective extraction and purification technologies, better delivery systems, and the discovery of new therapeutic targets through computational studies.

8.1. Xenon as a Treatment for Post-Traumatic Stress Disorder (PTSD) and Depressive Illnesses

Xenon’s ability to modulate NMDA receptors has spurred interest in its potential to treat neuropsychiatric conditions such as PTSD. Recent animal studies have shown that xenon can reduce the reconsolidation of traumatic memories by blocking NMDA receptor activity during the memory reconsolidation process [47]. If these findings are confirmed in human trials, xenon could offer a novel therapeutic approach for treating PTSD and other trauma-related disorders.
Shao et al. (2020) administered xenon gas via inhalation or xenon-rich saline intraperitoneally to male mice at subanesthetic doses and reported antidepressant-like and anxiolytic-like effects at 30 min [56].

8.2. Organ Preservation and Neuroprotection

Organ transplantation is increasing substantially due to improved surgical techniques and the growing needs of an ageing population. Argon and krypton have well-established efficacies as neuroprotectants and are being investigated as gases to preserve organs destined for transplantation. Their anti-apoptotic and anti-inflammatory properties are useful for maintaining tissue viability during cold storage and reperfusion, particularly in organs like the liver and kidneys [57]. Preclinical studies have demonstrated that argon-enriched preservation solutions can improve post-transplant organ function and reduce the risk of graft failure [58]. A very recent paper, published while this review was being completed, reported that inhaled krypton exhibited neuroprotective effects on photothrombotic ischemic stroke [59].

8.3. High-Altitude and Space Medicine

As well as its beneficial effects in intensive care, helium’s low density and ability to improve gas exchange have prompted research into its use in high-altitude and space medicine. At high altitudes or in critical illness where oxygen availability is reduced, heliox can be used to alleviate hypoxia and reduce the physical strain on the respiratory system [60]. In the context of space exploration, helium is being studied as a possible breathing gas for astronauts, particularly during extravehicular activities (EVA) in low-pressure and microgravity environments in which airway closure can occur [61]. Xenon can stimulate the production or red blood cells, potentially useful in hypoxic environments but leading to a ban by sporting bodies [62]. It is a putative hypoxia-inducible factor (HIF) activating agent [63]. Recent studies have also highlighted the potential for xenon to inhibit carbonic anhydrase and generate a beneficial effect on hypoxia by this mechanism [44]. As carbonic anhydrase is also a very useful target for glaucoma treatment, this discovery opens another possible therapeutic avenue for noble gas therapy.

8.4. Effects on Addiction

Recent studies have highlighted the potential of argon in treating drug addiction and dependence [64]. Inhaled xenon therapy was also found to result in the most rapid reduction of symptoms of opioid withdrawal and post-withdrawal states [65]. Similarly, xenon reduces alcohol-seeking behavior in rats and may therefore also interfere with craving in human alcoholics, unlike other gaseous anesthetics like N2O [66].

8.5. Computational Identification of New Noble Gas Biochemical Targets

Computational models have notably increased our understanding of how noble gases interact with biochemical targets and have identified numerous potential therapeutic applications. Recent models have predicted that xenon and krypton might interact with voltage-gated ion channels, potentially opening up a new area of research into their roles in pain management and cardioprotection [67].
As computational power continues to increase, models that simulate the behavior of noble gases at the molecular and systemic levels will become more sophisticated. The validity of large molecular docking studies of the binding of noble gases to protein targets has already been demonstrated. The reverse docking studies described in Section 6 provide insight into the mechanisms of known biomedical properties of noble gases but also identified many other proteins to which the heavier noble gases particularly are predicted to bind. Given the recent spectacular rise of deep learning and large language model (LLM) algorithms, there is a greatly increased scope for extending these studies from this large set of proteins to virtually any protein with a sequence. Developments in sequence-to-3D structure methods, exemplified by AlphaFold [68] and its competitors (awarded the Nobel Prize in Chemistry in 2024), mean that the number of structures potentially available for computational study is much larger [69]. So far, the AlphaFold predicted protein structure database contains over 214 million structures, 1000-fold more than the protein structure databank (rcsb.org) [70].
Machine learning techniques are already being used to predict the pharmacokinetics and dynamics of drugs in various tissues and would be expected to perform well for noble gases, paving the way for limited personalized medicine approaches for noble gas therapies, probably in conjunction with targeted gas delivery systems [71]. These advances will also aid in the discovery of next generation clinical applications for noble gases, particularly more effective and selective neuroprotection, cardioprotection, and the new medical applications highlighted above.
Clearly, these very powerful platform computational methods are very applicable to the study of other therapeutic gases such as CO, NO, N2O, H2S, SO2, H2, O2 and CO2.

8.6. Delivery Systems for Noble Gas Therapeutics

The cost of xenon (US $5000–$12,000 per kg) is a barrier to its wider use in medicine. Most clinical studies use masks, sometimes with gas recovery, to administer the xenon. Thus, most of the gas is lost, and only a small faction is delivered to the target sites. Drug delivery technologies have advanced markedly in this century and should be used to improve the efficiency of delivery of therapeutic noble gases [72]. The potential benefits are manifold. The efficiency of delivery of therapeutic gases to targets would be greatly increased, improving both efficacy and cost in the case of xenon. Delivery systems would overcome the low aqueous and blood solubility of the lighter noble gases, potentially negating the need for hyperbaric conditions to achieve therapeutic concentration at the target proteins. This would provide an opportunity for higher abundance, less expensive gases to be deployed across a wider range of therapeutic regimens, e.g., anesthesia. Even for xenon, noticeable neuroprotective effects require the gas to be inhaled at concentrations of 50–70%, critically limiting the fraction of inspired oxygen and potentially leading to hypoxic tissue damage [73]. New nanoparticle delivery systems are often designed to target specific tissues and/or feature triggered release mechanisms, ensuring that the maximum concentration of therapeutic occurs where it is needed [73].
Early proof of concepts studies have shown that liposomes, [74] nanoparticles, and nanobubbles can be effective ways to deliver xenon intravenously, with various physical or chemical modes of triggering cargo release, e.g., by ultrasound, being available. Nanobubbles, for example, can contain gaseous cargoes such as perfluoropentane and decafluoropentane and other therapeutic molecules. Being echogenic, they can also be triggered to release by ultrasound [75].
Despite the promising results from the few proof-of-concept experiments published to date, paradoxically, this has not stimulated an increase in experimental studies on therapeutic gas delivery systems. This is a missed opportunity and identifies a potentially valuable research gap that can be filled by exploiting the advances in nanotechnology and drug delivery technologies.

9. Environmental Considerations

Anesthetic gases can be potent greenhouse agents and there is increasing pressure to reduce their environmental impact. Xenon is not a greenhouse gas and hence, does not lead to global warming. The noble gases are chemically unreactive and should not affect the ozone layer like nitrous oxide and volatile anesthetics do [76]. The metric of global warming potential (GWP) and persistence over 20- or 100-year time frames is used to rank the impacts of chemicals released to the atmosphere. Carbon dioxide has, by definition, a GWP of 1. The IPCC uses the 100-year time horizon GWP (GWP100) to compare long-lived greenhouse gas effects. GWP100 for desflurane is 2540, for sevoflurane 130, for isoflurane 510, and for N2O 265. Worldwide anesthetic nitrous oxide use is estimated to contribute 1–3% of N2O’s global emissions [77].

10. Conclusions and Perspective

The chemically inert noble gases, once thought to be biologically inert, have proven to be valuable ‘atomic drugs’ in modern medicine. They all offer unique therapeutic and diagnostic benefits, from neuroprotection and anesthesia, to respiratory therapy and medical imaging. While challenges remain—particularly in terms of cost and accessibility—ongoing research and technological advances are likely to expand their clinical use. Computational studies are playing an increasingly important role in uncovering new molecular targets and predicting novel applications for these gases, heralding a new era of noble gas-based therapeutics.
As research on noble gas protein targets and methods for the efficient delivery of noble gases progresses, they will find even more applications across a broad spectrum of medical fields, enhancing patient outcomes and offering new treatment modalities for conditions ranging from ischemic brain injury to post-traumatic stress disorder. The integration of computational models and machine learning into noble gas research will accelerate the discovery of novel uses, potentially revolutionizing the way these inert elements are used in healthcare.

Funding

This research received no external funding.

Conflicts of Interest

The author declares no conflict of interest.

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Table 1. Physicochemical properties of the noble gases.
Table 1. Physicochemical properties of the noble gases.
GasAtomic Radius (pm)Polarizability (Å3) [4]logP Octanol/Water [5]Aqueous Solubility 20 °C (cm3/kg) [2]Blood Solubility 37 °C (cm3/kg) [6]
He310.200.288.68.0
Ne380.400.2810.59.3
Ar711.660.7433.630.0
Kr882.510.8959.460
Xe1084.061.28108.1146
Rn1205.01…230…
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Winkler, D. A. (2024). Noble Gases in Medicine: Current Status and Future Prospects. Oxygen, 4(4), 421-431. https://doi.org/10.3390/oxygen4040026

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