The first stages of nanomicelle formation captured in the sevoflurane trimer

Producción CientíficaSelf-aggregation of sevoflurane, an inhalable, fluorinated anesthetic, provides a challenge for current state-of-the-art high-resolution techniques due to its large mass and the variety of possible hydrogen bonds between monomers. Here we present the observation of sevoflurane trimer by chirped-pulse Fourier transform microwave spectroscopy, identified through the interplay of experimental and computational methods. The trimer (>600 Da), one of the largest molecular aggregates observed through rotational spectroscopy, does not resemble the binding (C–H···O) motif of the already characterized sevoflurane dimer, instead adapting a new binding configuration created predominantly from 17 CH···F hydrogen bonds that resembles a nanomicellar arrangement. The observation of such a heavy aggregate highlights the potential of rotational spectroscopy to study larger biochemical systems in the limit of spectroscopic congestion but also showcases the challenges ahead as the mass of the system increases.NSF Major Research Instrumentation program (grant CHE0960074)Ministerio de Ciencia, Innovación y Universidades - Fondo Europeo de Desarrollo Regional (grant PGC2018-098561-B-C22

π-Stacking Isomerism in Polycyclic Aromatic Hydrocarbons: The 2-Naphthalenethiol Dimer

Producción Científicaπ-Stacking is a common descriptor for face-to-face attractive forces between aromatic hydrocarbons. However, the physical origin of this interaction remains debatable. Here we examined π-stacking in a model homodimer formed by two thiol-substituted naphthalene rings. Two isomers of the 2-naphthalenethiol dimer were discovered using rotational spectroscopy, sharing a parallel-displaced crossed orientation and absence of thiol–thiol hydrogen bonds. One of the isomers presents C2 symmetry, structurally analogous to the global minimum of the naphthalene dimer. The experimental data were rationalized with molecular orbital calculations, revealing a shallow potential energy surface. Noncovalent interactions are dominated by dispersion forces according to SAPT energy decomposition. In addition, the reduced electronic density shows a diffuse and extended region of inter-ring interactions, compatible with the description of π-stacking as a competition between dispersion and Pauli repulsion forces

Development and validation of a clinical score to estimate progression to severe or critical state in Covid-19 pneumonia hospitalized patients

The prognosis of a patient with Covid-19 pneumonia is uncertain. Our objective was to establish a predictive model of disease progression to facilitate early decision-making. A retrospective study was performed of patients admitted with Covid-19 pneumonia, classified as severe (admission to the intensive care unit, mechanic invasive ventilation, or death) or non-severe. A predictive model based on clinical, analytical, and radiological parameters was built. The probability of progression to severe disease was estimated by logistic regression analysis. Calibration and discrimination (receiver operating characteristics curves and AUC) were assessed to determine model performance. During the study period 1,152 patients presented with Covid-19 infection, of whom 229 (19.9%) were admitted for pneumonia. During hospitalization, 51 (22.3%) progressed to severe disease, of whom 26 required ICU care (11.4); 17 (7.4%) underwent invasive mechanical ventilation, and 32 (14%) died of any cause. Five predictors determined within 24 hours of admission were identified: Diabetes, Age, Lymphocyte count, SaO2, and pH (DALSH score). The prediction model showed a good clinical performance, including discrimination (AUC 0.87 CI 0.81, 0.92) and calibration (Brier score = 0.11). In total, 0%, 12%, and 50% of patients with severity risk scores ≤5%, 6-25%, and >25% exhibited disease progression, respectively. A simple risk score based on five factors predicts disease progression and facilitates early decision-making according to prognosis.Carlos III Health Institute, Spain, Ministry of Economy and Competitiveness (SPAIN) and the European Regional Development Fund (FEDER)Instituto de Salud Carlos II