Exploring Unconventional σ-Hole Interactions: Computational Insights into the Interaction of XeO3 with Non-Aromatic Coordinating Solvents.

In order to control the explosiveness and shock sensitivity of XeO3 , we have investigated its plausible interaction with various non-aromatic coordinating solvents, serving as potential Lewis base donors, through density functional theory (DFT) calculations. Out of twenty six such solvents, the top ten were thus identified and then thoroughly examined by employing various computational tools such as the mapping of the electrostatic potential surface (MESP), Wiberg bond indices (WBIs), non-covalent interaction (NCI) plots, Bader's theory of atoms-in-molecules (AIM), natural bond orbital (NBO) analysis, and the energy decomposition analysis (EDA). The amphoteric nature of XeO3 was also explored by investigating the extent of back donation from the lone pair of Xe to the antibonding orbital of the donating atom/group of the solvent molecules. The C-H…O interactions were also found to be a contributing factor in the stabilization of these adducts. Although these aerogen-bonding interactions were found to be predominantly electrostatic, significant contributions from the orbital contributions, as well as dispersion interactions, were observed. The top three non-aromatic solvents (among the twenty six studied) which form the strongest adducts with XeO3 are proposed to be hexamethylphosphoramide (HMPA), N,N'-dimethylpropyleneurea (DMPU) and tetramethylethylenediamine (TMEDA).

Synergistic and Diminutive Effects between Regium and Aerogen Bonds.

The aerogen bond is formed in complexes of HCN-XeF2 O and C2 H4 -XeF2 O. The lone pair on the N atom of HCN is a better electron donor in the aerogen bond than the π electron on the C=C bond of C2 H4 . The coinage substitution strengthens the aerogen bond in MCN-XeF2 O (M=Cu, Ag, and Au) and its enhancing effect becomes larger in the Au

A comparative in vitro study of standard facemask jet nebulization and high-flow nebulization in bronchiolitis.

Aim of Study: The use of a nebulizer paired with high-flow nasal cannulas (HFNC) has been proposed for drug delivery in bronchiolitis. Particle size nebulized is a relevant factor determining the efficacy of the nebulization. We replicated in vitro the theoretical parameters most widely used in bronchiolitis and we compared the size of the droplet nebulized with a standard nebulizer and a nebulizer integrated into HFNC. Materials and Methods: We used laser diffraction to analyze the particle size nebulized (volume median diameter Dv50). The standard system was a jet nebulizer connected to a facemask with a flow rate of 8 L/min (JN). Three designs were used as nebulizers integrated into HFNC: a vibrating mesh nebulizer set 1) before (HFNC-BH) and 2) after (HFNC-AH) the humidifier, and 3) a jet nebulizer connected before the nasal cannula (HFNC-BNC). HFNC was used with neonatal (3-8 L/min) and infant cannulas (8-15 L/min). Results: Droplet size was similar among the three drugs studied. A lower particle size was obtained when using the nebulization system integrated into HFNC compared to the standard nebulizer, regardless of the flow rate and the nasal cannula used when the position of the nebulizer was before the nasal cannula (p < 0.05): 6.89 µm (JN), 2.49 µm (HFNC-BNC 3 L/min), 2.59 µm (HFNC-BNC 5 L/min), 2.44 µm (HFNC-BNC 8 L/min), 3.22 µm (HFNC-BNC 10 L/min), 3.23 µm (HFNC-BNC 13 L/min), 3.16 µm (HFNC-BNC 15 L/min). The particle size was lower in HFNC-BF compared to the HFNC-AH using neonatal nasal cannula (3-8 L/min) (p < 0.05). Conclusion: The use of a nebulizer integrated with HFNC has shown promising results in an experimental scenario of bronchiolitis. The particle size achieved with the nebulizer placed before the humidifier is equivalent to the one obtained via conventional nebulization, and it is even smaller when the integrated nebulizer is placed before the nasal cannulas.

Hole interactions of aerogen oxides with Lewis bases: an insight into σ-hole and lone-pair-hole interactions.

σ-Hole and lone-pair (lp)-hole interactions of aerogen oxides with Lewis bases (LB) were comparatively inspected in terms of quantum mechanics calculations. The ZOn ⋯ LB complexes (where Z = Kr and Xe, n = 1, 2, 3 and 4, and LB = NH3 and NCH) showed favourable negative interaction energies. The complexation features were explained in light of σ-hole and lp-hole interactions within optimum distances lower than the sum of the respective van der Waals radii. The emerging findings outlined that σ-hole interaction energies generally enhanced according to the following order: KrO4 ⋯ < KrO⋯ < KrO3⋯ < KrO2⋯LB and XeO4⋯ < XeO⋯ < XeO2⋯ < XeO3⋯LB complexes with values ranging from -2.23 to -12.84 kcal mol-1. Lp-hole interactions with values up to -5.91 kcal mol-1 were shown. Symmetry-adapted perturbation theory findings revealed the significant contributions of electrostatic forces accounting for 50-65% of the total attractive forces within most of the ZOn⋯LB complexes. The obtained observations would be useful for the understanding of hole interactions, particularly for the aerogen oxides, with application in supramolecular chemistry and crystal engineering.

-Comparison of σ/ π-hole aerogen-bonding interactions based on C2H4···NgOX2 (Ng = Kr, Xe; X = F, Cl, Br) complexes.

The geometric structure, energy properties, and electronic properties of the aerogen-bonding interaction formed by C2H4 and NgOX2 (Ng = Kr, Xe; X = F, Cl, Br) have been studied at the B2PLYP-D3(BJ)/ aug-cc-pVTZ (PP) level. Two kinds of aerogen-bonding interactions were observed among the title systems: the σ-hole and the π-hole complexes. The σ-hole aerogen-bonding complex has a binding energy in the range of - 6.29 ~ - 8.17 kcal/mol, which is the most stable. The binding energies of C2H4···NgOX2 increased as X = F < Cl < Br and Ng = KrOX2 < XeOX2 for the σ/π-hole aerogen-bonding complexes. The atoms in molecules (AIM), the non-covalent interaction (NCI) index, and the LMO-EDA energy decomposition analysis were adopted to study the nature of the σ/π-hole aerogen-bonding interaction. The results show that the electrostatic term contributes the most to the total interaction energy for the σ/π-hole aerogen-bonding complexes.

Unexpected Interruptions in the Inhaled Epoprostenol Delivery System: Incidence of Adverse Sequelae and Therapeutic Consequences in Critically Ill Patients.

OBJECTIVES: Inhaled epoprostenol is a continuously delivered selective pulmonary vasodilator that is used in patients with refractory hypoxemia, right heart failure, and postcardiac surgery pulmonary hypertension. Published data suggest that inhaled epoprostenol administration via vibrating mesh nebulizer systems may lead to unexpected interruptions in drug delivery. The frequency of these events is unknown. The objective of this study was to describe the incidence and clinical consequences of unexpected interruption in critically ill patients. DESIGN: Retrospective review and analysis. SETTING: Stanford University Hospital, a 605-bed tertiary care center. PATIENTS: Patients receiving inhaled epoprostenol in 2019. INTERVENTIONS: No interventions. MEASUREMENTS AND MAIN RESULTS: Clinical indication, duration of inhaled epoprostenol delivery, mode of respiratory support, and documented unexpected interruption. In 2019, there were 493 administrations of inhaled epoprostenol in 433 unique patients. Primary indications for inhaled epoprostenol were right heart dysfunction (n = 394; 79.9%) and hypoxemia (n = 92; 18.7%). Unexpected delivery interruptions occurred in 31 administrations (6.3%). Median duration of therapy prior to unexpected interruption was 2 days (interquartile range, 2-5 d). Respiratory support at the time of unexpected interruption was mechanical ventilation (61.3%), high-flow nasal cannula (35.5%), and noninvasive positive pressure ventilation (3.2%). Adverse sequelae of unexpected interruption included elevated pulmonary artery pressures (n = 12), systemic hypotension (n = 8), hypoxemia (n = 8), elevated central venous pressure (n = 4), and cardiac arrest (n = 1). Therapeutic interventions following unexpected interruption included initiation of inhaled nitric oxide (n = 21), increase in vasoactive medication (n = 2), and increase in respiratory support (n = 2). Most of the adverse events were Common Terminology Criteria for Adverse Events grade 3 and 4 (93.5%). CONCLUSIONS: A retrospective review of patients receiving inhaled epoprostenol via vibrating mesh nebulizer in 2019 revealed interruptions in 6.3% of administrations with most of these interruptions requiring therapeutic intervention. The true incidence of unexpected interruption and subsequent rate of unexpected interruption's requiring intervention is unknown due to the reliance on unexpected interruption identification and subsequent documentation in the electronic medical record. Sudden interruption in inhaled epoprostenol delivery can result in severe cardiopulmonary compromise, and on rare occasion, death.

Adapting the Aerogen Mesh Nebulizer for Dried Aerosol Exposures Using the PreciseInhale Platform.

Background: Many substances used in inhalation research are water soluble and can be administered as nebulized solutions. Typical examples are therapeutic, small-molecular agents, or macromolecules. Another category is a number of water-soluble agents used for airway diagnostics or disease modeling. Mesh nebulizers have facilitated well-controlled liquid aerosol exposures. Meanwhile, a benchtop inhalation platform, PreciseInhale, was developed for providing small-scale, well-controlled aerosol exposures in preclinical configurations. The purpose of the current research was to adapt the Aerogen mesh nebulizer to work within the PreciseInhale system for both cell culture and rodent exposures. Methods: The wet aerosols produced with the Aerogen Pro nebulizer were dried out in an aerosol holding chamber by supplying dry carrier air, which was provided by passing the incoming ambient air through a column with silica gel. The nebulizer was installed in an aerosol holding chamber between an upstream flow-rate pneumotach and a downstream aerosol monitor. By pulsing, the nebulizer output was reduced to 1%-10% of continuous operation to better match the exposure ventilation requirements. Additional drying was obtained by mantling the holding chamber with dried paper. Results and Conclusions: The nebulizer output was reduced to 3-30 µL/min and dried out before reaching the in vitro or in vivo exposure modules. Using solute concentrations in the range of 0.5%-2% (w/w), dried aerosols were produced with a mass median aerodynamic diameter of 1.5-2.0 µm, compared to the 4-5 µm droplets emitted by the nebulizer. Controlling the Aerogen nebulizer under a reduced output scheme within the PreciseInhale platform gave two major advantages: (i) by reducing aerosol output to better match exposure flow rates of single rodents, increased airway deposition yields were obtained in a range of 1%-10% relative to the nebulized amount of test substance and (ii) shrinking aerosol particle sizes through drying improved the peripheral lung deposition of test aerosols.

The Aerogen® Solo Is an Alternative to the Small Particle Aerosol Generator (SPAG-2) for Administration of Inhaled Ribavirin.

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

Is Aerogen-π Interaction Capable of Initiating the Noncovalent Chemistry of Group 18?

The interactions between atoms of noble gases and π systems are generally considered as van der Waals interaction, which have not attracted attention yet. Herein, we present high-level ab initio calculations to show the unexpected noncovalent interaction between a covalently bonded noble gas atom and a delocalized aromatic π electron using XeO3⋅benzene as the prototype. The CCSD(T)/CBS reference data show its strength amounting to -10.2 kcal mol(-1), comparable to a typical H-bond or an anion-π interaction. The energy decomposition analysis reveals that the aerogen-π interaction is favored by the electrostatic interaction (27.7%), the induction (13.4%), and the dispersion (21.6%). This interaction may prompt us to consider the noncovalent chemistry of aerogen derivatives in the near future.