Local Xenon-Protein Interaction Produces Global Conformational Change and Allosteric Inhibition in Lysozyme.

Noble gases have well-established biological effects, yet their molecular mechanisms remain poorly understood. Here, we investigated, both experimentally and computationally, the molecular modes of xenon (Xe) action in bacteriophage T4 lysozyme (T4L). By combining indirect gassing methods with a colorimetric lysozyme activity assay, a reversible, Xe-specific (20 ± 3)% inhibition effect was observed. Accelerated molecular dynamic simulations revealed that Xe exerts allosteric inhibition on the protein by expanding a C-terminal hydrophobic cavity. Xe-induced cavity expansion results in global conformational changes, with long-range transduction distorting the active site where peptidoglycan binds. Interestingly, the peptide substrate binding site that enables lysozyme specificity does not change conformation. Two T4L mutants designed to reshape the C-terminal Xe cavity established a correlation between cavity expansion and enzyme inhibition. This work also highlights the use of Xe flooding simulations to identify new cryptic binding pockets. These results enrich our understanding of Xe-protein interactions at the molecular level and inspire further biochemical investigations with noble gases.

Spectroscopy of Laser-Induced Dielectric Breakdown Plasma in Mixtures of Air with Inert Gases Ar, He, Kr, and Xe.

The generation of ozone and nitrogen oxides by laser-induced dielectric breakdown (LIDB) in mixtures of air with noble gases Ar, He, Kr, and Xe is investigated using OES and IR spectroscopy, mass spectrometry, and absorption spectrophotometry. It is shown that the formation of NO and NO2 noticeably depends on the type of inert gas; the more complex electronic configuration and the lower ionization potential of the inert gas led to increased production of NO and NO2. The formation of ozone occurs mainly due to the photolytic reaction outside the gas discharge zone. Equilibrium thermodynamic analysis showed that the formation of NO in mixtures of air with inert gases does not depend on the choice of an inert gas, while the equilibrium concentration of the NO+ ion decreases with increasing complexity of the electronic configuration of an inert gas.

Identifying medically relevant xenon protein targets by in silico screening of the structural proteome.

In a previous study, in silico screening of the binding of almost all proteins in the Protein Data Bank to each of the five noble gases xenon, krypton, argon, neon, and helium was reported. This massive and rich data set requires analysis to identify the gas-protein interactions that have the best binding strengths, those where the binding of the noble gas occurs at a site that can modulate the function of the protein, and where this modulation might generate clinically relevant effects. Here, we report a preliminary analysis of this data set using a rational, heuristic score based on binding strength and location. We report a partial prioritized list of xenon protein targets and describe how these data can be analyzed, using arginase and carbonic anhydrase as examples. Our aim is to make the scientific community aware of this massive, rich data set and how it can be analyzed to accelerate future discoveries of xenon-induced biological activity and, ultimately, the development of new "atomic" drugs.

Hitting the Bull's Eye: Stable HeBeOH+ Complex.

It is now known that the heavier noble gases (Ng=Ar-Rn) show some varying degrees of reactivity with a gradual increase in reactivity along Ar-Rn. However, because of their very small size and very high ionization potential, helium and neon are the hardest targets to crack. Although few neon complexes are isolated at very low temperatures, helium needs very extreme situations like very high pressure. Here, we find that protonated BeO, BeOH+ can bind helium and neon spontaneously at room temperature. Therefore, extreme conditions like very low temperature and/or high pressure will not be required for their experimental isolation. The Ng-Be bond strength is very high for their heavier homologs and the bond strength shows a gradual increase from He to Rn. Moreover, the Ng-Be attractive energy is almost exclusively originated from the orbital interaction which is composed of one Ng(s/pσ )→BeOH+ σ-donation and two weaker Ng(pπ )→BeOH+ π-donations, except for helium. Helium uses its low-lying vacant 2p orbitals to accept π-electron density from BeOH+ . Previously, such electron-accepting ability of helium was used to explain a somewhat stronger helium bond than neon for neutral complexes. However, the present results indicate that such π-back donations are too weak in nature to decide any energetic trend between helium and neon.

Monitoring Noble Gases (Xe and Kr) and Aerosols (Cs and Rb) in a Molten Salt Reactor Surrogate Off-Gas Stream Using Laser-Induced Breakdown Spectroscopy (LIBS).

This study with surrogate materials shows that laser-induced breakdown spectroscopy (LIBS) is a robust tool with promising capability toward monitoring gaseous (Xe and Kr) and aerosol (Cs and Rb) species in an off-gas stream from a molten salt reactor (MSR). MSRs will continually evolve fission products into the cover gas flowing across the reactor headspace. The cover gas entrains Xe and Kr gases, along with aerosol particles, before passing into an off-gas treatment system. Univariate models of Xe and Kr peaks showed a strong correlation to concentration indicated by their coefficients of determination of 0.983 and 0.997, respectively. Multivariate models were built for all four analytes using partial least squares regression coupled with preprocessing steps including normalization, trimming, and/or genetic algorithm derived filters. The models were evaluated by predicting the concentrations of the analytes in four validation samples, in which all calibration models were successfully validated at a confidence interval of 99.9%. Lastly, pressure controllers were used to regulate the mass flow rate of Kr flowing into the measurement cell in sinusoidal and stepwise waveforms to test the real-time monitoring capabilities of the regression models. Both univariate and partial least squares Kr models were able to successfully quantify the gas concentration in the real-time evaluation. The root mean squared error of prediction (RMSEP) values for these real-time tests were calculated to be 0.051, 0.060, and 0.121 mol% demonstrating the measurement systems' capability to perform online monitoring with acceptable accuracy.

On the Proton-Bound Noble Gas Dimers (Ng-H-Ng)+ and (Ng-H-Ng')+ (Ng, Ng'= He-Xe): Relationships betweenStructure, Stability, and Bonding Character.

The structure, stability, and bonding character of fifteen (Ng-H-Ng)+ and (Ng-H-Ng')+ (Ng, Ng' = He-Xe) compounds were explored by theoretical calculations performed at the coupled cluster level of theory. The nature of the stabilizing interactions was, in particular, assayed using a method recently proposed by the authors to classify the chemical bonds involving the noble-gas atoms. The bond distances and dissociation energies of the investigated ions fall in rather large intervals, and follow regular periodic trends, clearly referable to the difference between the proton affinity (PA) of the various Ng and Ng'. These variations are nicely correlated with the bonding situation of the (Ng-H-Ng)+ and (Ng-H-Ng')+. The Ng-H and Ng'-H contacts range, in fact, between strong covalent bonds to weak, non-covalent interactions, and their regular variability clearly illustrates the peculiar capability of the noble gases to undergo interactions covering the entire spectrum of the chemical bond.

Theoretical Prediction on the New Types of Noble Gas Containing Anions OBONgO- and OCNNgO- (Ng = He, Ar, Kr and Xe).

The fluorine-less noble gas containing anions OBONgO- and OCNNgO- have been studied by correlated electronic structure calculation and density functional theory. The obtained energetics indicates that for Ng = Kr and Xe, these anions should be kinetically stable at low temperature. The molecular structures and electron density distribution suggests that these anions are stabilized by ion-induced dipole interactions with charges concentrated on the electronegative OBO and OCN groups. The current study shows that in addition to the fluoride ion, polyatomic groups with strong electronic affinities can also form stable noble gas containing anions of the type Y-…NgO.

Noble-Gas Chemistry More than Half a Century after the First Report of the Noble-Gas Compound.

Recent development in the synthesis and characterization of noble-gas compounds is reviewed, i.e., noble-gas chemistry reported in the last five years with emphasis on the publications issued after 2017. XeF2 is commercially available and has a wider practical application both in the laboratory use and in the industry. As a ligand it can coordinate to metal centers resulting in [M(XeF2)x]n+ salts. With strong Lewis acids, XeF2 acts as a fluoride ion donor forming [XeF]+ or [Xe2F3]+ salts. Latest examples are [Xe2F3][RuF6]·XeF2, [Xe2F3][RuF6] and [Xe2F3][IrF6]. Adducts NgF2·CrOF4 and NgF2·2CrOF4 (Ng = Xe, Kr) were synthesized and structurally characterized at low temperatures. The geometry of XeF6 was studied in solid argon and neon matrices. Xenon hexafluoride is a well-known fluoride ion donor forming various [XeF5]+ and [Xe2F11]+ salts. A large number of crystal structures of previously known or new [XeF5]+ and [Xe2F11]+ salts were reported, i.e., [Xe2F11][SbF6], [XeF5][SbF6], [XeF5][Sb2F11], [XeF5][BF4], [XeF5][TiF5], [XeF5]5[Ti10F45], [XeF5][Ti3F13], [XeF5]2[MnF6], [XeF5][MnF5], [XeF5]4[Mn8F36], [Xe2F11]2[SnF6], [Xe2F11]2[PbF6], [XeF5]4[Sn5F24], [XeF5][Xe2F11][CrVOF5]·2CrVIOF4, [XeF5]2[CrIVF6]·2CrVIOF4, [Xe2F11]2[CrIVF6], [XeF5]2[CrV2O2F8], [XeF5]2[CrV2O2F8]·2HF, [XeF5]2[CrV2O2F8]·2XeOF4, A[XeF5][SbF6]2 (A = Rb, Cs), Cs[XeF5][BixSb1-xF6]2 (x = ~0.37-0.39), NO2XeF5(SbF6)2, XeF5M(SbF6)3 (M = Ni, Mg, Zn, Co, Cu, Mn and Pd) and (XeF5)3[Hg(HF)]2(SbF6)7. Despite its extreme sensitivity, many new XeO3 adducts were synthesized, i.e., the 15-crown adduct of XeO3, adducts of XeO3 with triphenylphosphine oxide, dimethylsulfoxide and pyridine-N-oxide, and adducts between XeO3 and N-bases (pyridine and 4-dimethylaminopyridine). [Hg(KrF2)8][AsF6]2·2HF is a new example of a compound in which KrF2 serves as a ligand. Numerous new charged species of noble gases were reported (ArCH2+, ArOH+, [ArB3O4]+, [ArB3O5]+, [ArB4O6]+, [ArB5O7]+, [B12(CN)11Ne]-). Molecular ion HeH+ was finally detected in interstellar space. The discoveries of Na2He and ArNi at high pressure were reported. Bonding motifs in noble-gas compounds are briefly commented on in the last paragraph of this review.

Leading Interaction Components in the Structure and Reactivity of Noble Gases Compounds.

The nature, strength, range and role of the bonds in adducts of noble gas atoms with both neutral and ionic partners have been investigated by exploiting a fine-tuned integrated phenomenological-theoretical approach. The identification of the leading interaction components in the noble gases adducts and their modeling allows the encompassing of the transitions from pure noncovalent to covalent bound aggregates and to rationalize the anomalous behavior (deviations from noncovalent type interaction) pointed out in peculiar cases. Selected adducts affected by a weak chemical bond, as those promoting the formation of the intermolecular halogen bond, are also properly rationalized. The behavior of noble gas atoms excited in their long-life metastable states, showing a strongly enhanced reactivity, has been also enclosed in the present investigation.

Effect of different firing atmospheres on debonding strength of dental porcelain fused to commercially pure titanium.

An in vitro investigation was performed to evaluate the bonding characteristics of porcelain fused to metal (PFM)/commercially pure titanium (cp Ti, grade II) in three firing atmospheres of under vacuum and using two noble gases argon (Ar) and helium (He). Three groups of porcelain veneers firing under vacuum, Ar, and He were prepared to evaluate the bonding of porcelain fused to the cold-rolled cp Ti. The bond strength of PFM durability by a three-point bending test, phases, microhardness of cp Ti after firing processes, and fractures were measured and evaluated. Results show the microhardness of cp Ti in group of porcelain firing under He atmosphere was significantly lower than that of the two other groups, which were in vacuum and Ar (P < .05). X-ray diffraction showed the He group produced in relatively small amounts of TiO2 and TiO oxides than other groups but featured relatively high quantity of airhole defects in the porcelain body leading to the lowest bond strength. The Ar group presented the highest bond strength of comparing with the groups under vacuum and using He (P < .05). Although the firing processes in He could efficiently prevent the diffusion of oxygen into Ti, the porcelain-cp Ti bond strength using Ar protective atmosphere presented the advantage to achieve clinical requirement because porcelain firing under He revealed prominent voids and defects within the body of porcelain.

The Halogen-Bond Nature in Noble Gas-Dihalogen Complexes from Scattering Experiments and Ab Initio Calculations.

In order to clarify the nature of the halogen bond (XB), we considered the prototype noble gas-dihalogen molecule (Ng-X2) systems, focusing on the nature, range, and strength of the interaction. We exploited data gained from molecular beam scattering experiments with the measure of interference effects to obtain a suitable formulation of the interaction potential, with the support of high-level ab initio calculations, and charge displacement analysis. The essential interaction components involved in the Ng-X2 adducts were characterized, pointing at their critical balance in the definition of the XB. Particular emphasis is devoted to the energy stability of the orientational Ng-X2 isomers, the barrier for the X2 hindered rotation, and the influence of the X2 electronic state. The present integrated study returns reliable force fields for molecular dynamic simulations in Ng-X2 complexes that can be extended to systems with increasing complexity and whose properties depend on the selective formation of XB.

How Far Can One Push the Noble Gases Towards Bonding?: A Personal Account.

Noble gases (Ngs) are the least reactive elements in the periodic table towards chemical bond formation when compared with other elements because of their completely filled valence electronic configuration. Very often, extreme conditions like low temperatures, high pressures and very reactive reagents are required for them to form meaningful chemical bonds with other elements. In this personal account, we summarize our works to date on Ng complexes where we attempted to theoretically predict viable Ng complexes having strong bonding to synthesize them under close to ambient conditions. Our works cover three different types of Ng complexes, viz., non-insertion of NgXY type, insertion of XNgY type and Ng encapsulated cage complexes where X and Y can represent any atom or group of atoms. While the first category of Ng complexes can be thermochemically stable at a certain temperature depending on the strength of the Ng-X bond, the latter two categories are kinetically stable, and therefore, their viability and the corresponding conditions depend on the size of the activation barrier associated with the release of Ng atom(s). Our major focus was devoted to understand the bonding situation in these complexes by employing the available state-of-the-art theoretic tools like natural bond orbital, electron density, and energy decomposition analyses in combination with the natural orbital for chemical valence theory. Intriguingly, these three types of complexes represent three different types of bonding scenarios. In NgXY, the strength of the donor-acceptor Ng→XY interaction depends on the polarizing power of binding the X center to draw the rather rigid electron density of Ng towards itself, and sometimes involvement of such orbitals becomes large enough, particularly for heavier Ng elements, to consider them as covalent bonds. On the other hand, in most of the XNgY cases, Ng forms an electron-shared covalent bond with X while interacting electrostatically with Y representing itself as [XNg]+Y-. Nevertheless, in some of the rare cases like NCNgNSi, both the C-Ng and Ng-N bonds can be represented as electron-shared covalent bonds. On the other hand, a cage host is an excellent moiety to examine the limits that can be pushed to attain bonding between two Ng atoms (even for He) at high pressure. The confinement effect by a small cage-like B12N12 can even induce some covalent interaction within two He atoms in the He2@B12N12 complex.

Using Noble Gases to Assess the Ocean's Carbon Pumps.

Natural mechanisms in the ocean, both physical and biological, concentrate carbon in the deep ocean, resulting in lower atmospheric carbon dioxide. The signals of these carbon pumps overlap to create the observed carbon distribution in the ocean, making the individual impact of each pump difficult to disentangle. Noble gases have the potential to directly quantify the physical carbon solubility pump and to indirectly improve estimates of the biological organic carbon pump. Noble gases are biologically inert, can be precisely measured, and span a range of physical properties. We present dissolved neon, argon, and krypton data spanning the Atlantic, Southern, Pacific, and Arctic Oceans. Comparisons between deep-ocean observations and models of varying complexity enable the rates of processes that control the carbon solubility pump to be quantified and thus provide an important metric for ocean model skill. Noble gases also provide a powerful means of assessing air-sea gas exchange parameterizations.

Mechanoluminescence of Ce/Tb inorganic salts in methane-acetylene mixtures with inert gases.

The mechanoluminescence of cerium (Ce) and terbium (Tb) lanthanide salts is studied in hydrocarbon [methane (CH4 ) and acetylene (C2 H2 )] and inert [helium (He), neon (Ne), argon (Ar), krypton (Kr), and xenon (Xe)] gaseous mixtures. The lines of *N2 , *Ln3+ , inert gases, *CH, and *C2 radicals resulted from the mechanochemical decomposition of CH4 and C2 H2 are observed in the emission spectrum. The luminescence intensity of the inert gases decreases with the hydrocarbon gas concentration in the mixture. The intensities of the *CH or *C2 bands remains almost unchanged within 15-100 vol% of CH4 or C2 H2 in the mixture. When the concentration of CH4 or C2 H2 is lower than 15%, the intensities of the CH or C2 bands increase achieving their maxima at 0.5-3% of the hydrocarbon. This is probably due to the optimal compositions of the mixtures with the most efficient generation of electrical discharges responsible for mechanoluminescence.

Anesthetic Molecule Interaction of Noble Gases with Proteins and Lipids and their Effect: A Review.

Surgical operations are impossible without administering proper analgesia. Advancement in the field of anesthesia has invariably resulted in the accomplishment of all surgical processes without any inconvenience. Admittedly, the use of noble gas is on the decline. The noble gases may not interact chemically with any other substance under normal temperature and pressure but they may interact with proteins and lipids. Different anesthetic molecules may stimulate either proteins or lipids in membrane. There is a connection between the anesthetic molecules and the hydrophobic region of the membrane. In the present review, we attempt to highlight the interaction between the anesthetic molecule with proteins and lipids and their effects. We sketched few noble gases and some other existing molecules such as halothane and alcohol which interacted with proteins and lipids.

Use of computational fluid dynamics for improving freeze-dryers design and process understanding. Part 2: Condenser duct and valve modelling.

This manuscript shows how computational models, mainly based on Computational Fluid Dynamics (CFD), can be used to simulate different parts of an industrial freeze-drying equipment and to properly design them; in particular in this part the duct connecting the chamber with the condenser, with its valves, is considered, while the chamber design and its effect on drying kinetics have been investigated in Part 1. Such an approach allows a much deeper process understanding and assessment of the critical aspects of lyophilisation. This methodology will be demonstrated on freeze-drying equipment of different sizes, investigating influence of valve type (butterfly and mushroom) and shape on duct conductance and critical flow conditions. The role of the inlet and boundary conditions considered has been assessed, also by modelling the whole apparatus including chamber and condenser, and the influence of the duct diameter has been discussed; the results show a little dependence of the relationship between critical mass flux and chamber pressure on the duct size. Results concerning the fluid dynamics of a simple disk valve, a profiled butterfly valve and a mushroom valve installed in a medium size horizontal condenser are presented. Also in these cases the maximum allowable flow when sonic flow conditions are reached can be described by a correlation similar to that found valid for empty ducts; for the mushroom valve the parameters are dependent on the valve opening length. The possibility to use the equivalent length concept, and to extend the validity of the results obtained for empty ducts will be also discussed. Finally the presence of the inert gas modifies the conductance of the duct, reducing the maximum flow rate of water that can be removed through it before the flow is choked; this also requires a proper over-sizing of the duct (or duct-butterfly valve system).

Inert Gas Deactivates Protein Activity by Aggregation.

Biologically inert gases play important roles in the biological functionality of proteins. However, researchers lack a full understanding of the effects of these gases since they are very chemically stable only weakly absorbed by biological tissues. By combining X-ray fluorescence, particle sizing and molecular dynamics (MD) simulations, this work shows that the aggregation of these inert gases near the hydrophobic active cavity of pepsin should lead to protein deactivation. Micro X-ray fluorescence spectra show that a pepsin solution can contain a high concentration of Xe or Kr after gassing, and that the gas concentrations decrease quickly with degassing time. Biological activity experiments indicate a reversible deactivation of the protein during this gassing and degassing. Meanwhile, the nanoparticle size measurements reveal a higher number of "nanoparticles" in gas-containing pepsin solution, also supporting the possible interaction between inert gases and the protein. Further, MD simulations indicate that gas molecules can aggregate into a tiny bubble shape near the hydrophobic active cavity of pepsin, suggesting a mechanism for reducing their biological function.

Diverging effects of isotopic fractionation upon molecular diffusion of noble gases in water: mechanistic insights through ab initio molecular dynamics simulations.

Atmospheric noble gases are routinely used as natural tracers to analyze gas transfer processes in aquatic systems. Their isotopic ratios can be employed to discriminate between different physical transport mechanisms by comparison to the unfractionated atmospheric isotope composition. In many applications of aquatic systems molecular diffusion was thought to cause a mass dependent fractionation of noble gases and their isotopes according to the square root ratio of their masses. However, recent experiments focusing on isotopic fractionation within a single element challenged this broadly accepted assumption. The determined fractionation factors of Ne, Ar, Kr and Xe isotopes revealed that only Ar follows the prediction of the so-called square root relation, whereas within the Ne, Kr and Xe elements no mass-dependence was found. The reason for this unexpected divergence of Ar is not yet understood. The aim of our computational exercise is to establish the molecular-resolved mechanisms behind molecular diffusion of noble gases in water. We make the hypothesis that weak intermolecular interactions are relevant for the dynamical properties of noble gases dissolved in water. Therefore, we used ab initio molecular dynamics to explicitly account for the electronic degrees of freedom. Depending on the size and polarizability of the hydrophobic particles such as noble gases, their motion in dense and polar liquids like water is subject to different diffusive regimes: the inter-cavity hopping mechanism of small particles (He, Ne) breaks down if a critical particle size achieved. For the case of large particles (Kr, Xe), the motion through the water solvent is governed by mass-independent viscous friction leading to hydrodynamical diffusion. Finally, Ar falls in between the two diffusive regimes, where particle dispersion is propagated at the molecular collision time scale of the surrounding water molecules.

Anisotropic noble metal nanoparticles: Synthesis, surface functionalization and applications in biosensing, bioimaging, drug delivery and theranostics.

Anisotropic nanoparticles have fascinated scientists and engineering communities for over a century because of their unique physical and chemical properties. In recent years, continuous advances in design and fabrication of anisotropic nanoparticles have opened new avenues for application in various areas of biology, chemistry and physics. Anisotropic nanoparticles have the plasmon absorption in the visible as well as near-infrared (NIR) region, which enables them to be used for crucial applications such as biological imaging, medical diagnostics and therapy ("theranostics"). Here, we describe the progress in anisotropic nanoparticles achieved since the millennium in the area of preparation including various shapes and modification of the particle surface, and in areas of application by providing examples of applications in biosensing, bio-imaging, drug delivery and theranostics. Furthermore, we also explain various mechanisms involved in cellular uptake of anisotropic nanoparticles, and conclude with our opinion on various obstacles that limit their applications in biomedical field. STATEMENT OF SIGNIFICANCE: Anisotropy at the molecular level has always fascinated scientists and engineering communities for over a century, however, the research on novel methods through which shape and size of nanoparticles can be precisely controlled has opened new avenues for anisotropic nanoparticles in various areas of biology, chemistry and physics. In this manuscript, we describe progress achieved since the millennium in the areas of preparation of various shapes of anisotropic nanoparticles, investigate various methods involved in modifying the surface of these NPs, and provide examples of applications in biosensing and bio-imaging, drug delivery and theranostics. We also present mechanisms involved in cellular uptake of nanoparticles, describe different methods of preparation of anisotropic nanoparticles including biomimetic and photochemical synthesis, and conclude with our opinion on various obstacles that limit their applications in biomedical field.

An overview of heavy-atom derivatization of protein crystals.

Heavy-atom derivatization is one of the oldest techniques for obtaining phase information for protein crystals and, although it is no longer the first choice, it remains a useful technique for obtaining phases for unknown structures and for low-resolution data sets. It is also valuable for confirming the chain trace in low-resolution electron-density maps. This overview provides a summary of the technique and is aimed at first-time users of the method. It includes guidelines on when to use it, which heavy atoms are most likely to work, how to prepare heavy-atom solutions, how to derivatize crystals and how to determine whether a crystal is in fact a derivative.