A new 1:1 cocrystal (L-Asc–Pic) of L-ascorbic acid (vitamin C) with picolinic acid was prepared as a powder and as single crystals. The crystal structure was solved and refined from single-crystal X-ray diffraction (SCXRD) data collected at 293 (2) and 100 (2) K. The samples of the L-Asc–Pic cocrystal were characterized by elemental (HCNS) analysis and titrimetric methods, TG/DTG/DSC, and IR and Raman spectroscopy. The asymmetric unit comprises a picolinic acid zwitterion and an L-ascorbic acid molecule. The stabilization energy of intermolecular interactions involving hydrogen bonds, the vibrational spectrum and the energies of the frontier molecular orbitals were calculated using the GAUSSIAN09 and the CrystalExplorer17 programs. The charge distribution on the atoms of the L-Asc–Pic cocrystal, L-ascorbic acid itself and its 12 known cocrystals (structures from Version 5.40 of the Cambridge Structural Database) were calculated by the methods of Mulliken, Voronoi and Hirshfeld charge analyses (ADF) at the bp86/TZ2P+ level of theory. The total effective charges and conformations of the L-ascorbic acid molecules in the new and previously reported cocrystals were compared with those of the two symmetry-independent molecules in the crystals of L-ascorbic acid. A correlation between molecular conformation and its effective charge is discussed.
Acute respiratory distress syndrome (ARDS) is the main danger to the life of patients with pneumonia caused by SARS-CoV-2. At the same time, respiratory failure (RF) after ARDS can persist for a long time despite intensive therapy. Therefore, it is important to develop new effective approaches for restoring the ventilation function of the lungs after COVID-19. Here, we present a case report of effective application of short-term inhalations of xenon-oxygen (Xe/O
2
) gas mixture for treatment of RF and neuropsychiatric disorders (NPD) associated with COVID-19. The patient inhaled a gas mixture of 70 % Xe and 30 % O
2
. We used multispiral computed tomography, evaluated psychometry, studied hematological and biochemical blood parameters, and applied some other methods of clinical studies to assess the therapeutic effectiveness of Xe inhalation. Also, we studied the mechanism of action of xenon with computer modeling. The clinical case showed the high efficacy of Xe/O
2
mixture for treating severe RF and NPD after SARS-CoV-2 infection. Xenon inhalations dramatically increased oxygen saturation and the degree of pneumatization of the lungs. We found out that in coronavirus pneumonia, saturated phospholipids of surfactant are transferred to the solid-ordered phase, which disrupts the surface tension of the alveoli and alveolar gas exchange. Using molecular modeling methods, we demonstrated that the xenon atom increases the distance between the acyl chains of phospholipids due to the van der Waals dispersion interaction. These changes allow for the phase transition of phospholipids from the solid-ordered phase to the liquid phase and restore the functional activity of the surfactant. The findings suggest the feasibility of conducting studies on the effectiveness of Xe/O
2
inhalations for treating ARDS in SARS-CoV-2 infection.
The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O
2
gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O
2
gas mixture relieved manifestations of ventilation insufficiency and increased SpO
2
and pneumatization of the terminal parts of the lungs.
The effects of inhalations of an oxygen-xenon (70%/30%) mixture were studied in two models of acute respiratory distress syndrome caused by intratracheal administration of 0.5 mg/kg LPS or 0.04 ml acidin-pepsin (pH 1.2). Inhalation of the oxygen-xenon mixture inhibited the development and reduced the intensity of the inflammatory process in the lung tissue, which was assessed by the dynamics of lung weight and body weight of animals: the therapeutic exposure decreased both parameters. It was found that the thrombogenic stimulus, pathognomonic for the development of acute respiratory distress syndrome, decreased under the effect of oxygen-xenon inhalations, while the level of natural anticoagulant antithrombin III increased.
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