Experimental and theoretical insights into the formation of weak hydrogen bonds and H center dot center dot center dot H bonding interactions in the solid-state structure of two eucalyptol derivatives

Two eucalyptol derivatives, namely 1,3,3-trimethyl-2-oxabicycle[2.2.2]oct-5-yl acetate (4) and 1,3,3trimethyl-2-oxabicycle[2.2.2]oct-5,8-yl acetate (6) have been synthesized and characterized. Their crystal structures have been solved by single-crystal X-ray diffraction methods indicating that the molecular conformation of both compounds is stabilized by intramolecular C-H center dot center dot center dot O bonds between the H-atoms of the methyl group from the eucalyptol moiety and the O-atom of the acetoxy group. In addition, we have performed a detailed investigation of the intermolecular interactions that stabilize the crystal packing of both structures by using Hirshfeld surface analysis and their associated two-dimensional fingerprint plots. The analysis reveals that the solid-state structure of compounds 4 and 6 is mainly stabilized by C-H center dot center dot center dot O hydrogen bonds and H center dot center dot center dot H bonding interactions. These interactions have also been described and studied energetically using DFT calculations. The nature and strength of these intermolecular contacts have been rationalized by using several computational tools including molecular electrostatic potential (MEP) surfaces, natural bond orbital analysis (NBO), Bader's theory of atoms in molecules (QTAIM) and non-covalent interaction plot (NCI plot) index methods. Furthermore, the intermolecular contacts observed in the crystal lattice of both compounds were experimentally studied through vibrational (IR and Raman) and H-1 and C-13 NMR spectra. The computational molecular docking analysis of the compounds has been carried out against five potential leishmanial drug targets and the main protease of SARS-CoV-2.

[Enoxaparin dose associated with decreased risk of death in COVID-19]

BACKGROUND: In December 2019, an outbreak of COVID-19 was reported for the first time. This disease has caused millions of deaths worldwide. To date multiple drugs have been tried, without finding an effective treatment yet. OBJECTIVE: To describe the evolution and the pharmacological treatment used in patients hospitalized due to COVID-19. MATERIAL AND METHODS: Observational study in 200 patients hospitalized due to COVID-19 in a regional hospital of Acapulco who were admitted between March and July 2020. The characteristics, pharmacological treatment and evolution of the patients were identified. Univariate, bivariate and multivariate analyses were performed. RESULTS: 60% of the patients were male, 83% had at least one comorbidity, 56% died. The most used drug was enoxaparin, of which receiving a 60 mg dose was associated with a lower risk of death, compared to receiving 40 mg. Having received hydroxychloroquine, methylprednisolone, moxifloxacin and being 60 years or older was associated with a higher risk of progressing to death. CONCLUSIONS: There was a high mortality. The most used drug was enoxaparin, of which using doses of 60 mg reduced the risk of death.