Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Novel Noncovalent Interactions in Catalysis: A Focus on Halogen, Chalcogen, and Anion-pi Bonding

Noncovalent interactions play an important role in many biological and chemical processes. Among these, hydrogen bonding is very well studied and is already routinely used in organocatalysis. This Short Review focuses on three other types of promising noncovalent interactions. Halogen bonding, chalcogen bonding, and anion-pi bonding have been introduced into organocatalysis in the last few years and could become important alternate modes of activation to hydrogen bonding in the future

Asymmetric [N–I–N]+ halonium complexes in solution?

Assessment of the solution equilibria of [bis(pyridine)iodine(I)]+ complexes by ESI-MS and NMR reveals the preference of iodine(I) to form complexes with a more basic pyridine. Mixtures of symmetric [bis(pyridine)iodine(I)]+ complexes undergo statistical ligand exchange, with a predominant entropic driving force favoring asymmetric systems. The influence of ligand basicity, concentration, temperature, and ligand composition is evaluated. Our findings are expected to facilitate the investigations, and the supramolecular and synthetic applications of halonium ions’ halogen bonds.peerReviewe

Origin of the Catalytic Effects of Molecular Iodine: A Computational Analysis

Molecular iodine is an excellent catalyst for many organic transformations, but the origin of its catalytic activity is still unknown. To answer this question, we have analyzed four iodine-catalyzed reactions by density functional theory. Our calculations reveal that molecular iodine significantly reduces the activation free energies (-7.6 < Delta G(double dagger) < -1.8 kcal mol(-1)) for reactions involving alpha,beta-unsaturated carbonyls or nitrostyrenes. Closer analysis of the nature of the interaction between iodine and the corresponding Michael acceptors suggests that halogen bonding is the origin of the catalytic activity. The computational and experimental studies show that hidden Bronsted acid catalysis as a competing pathway due to the formation of hydrogen iodide via hypoiodites in aprotic solvents seems less likely for these reactions

Probing Halogen Bonds by Scalar Couplings

As halogen bonding is a weak, transient interaction, its description in solution is challenging. We demonstrate that scalar coupling constants (J) are modulated by halogen bonding. The binding-induced magnitude change of one-bond couplings, even up to five bonds from the interaction site, correlates to the interaction strength. We demonstrate this using the NMR data of 42 halogen-bonded complexes in dichloromethane solution and by quantum chemical calculations. Our observation puts scalar couplings into the toolbox of methods for characterization of halogen bond complexes in solution and paves the way for their applicability for other types of weak σ-hole interactions

Activation of Michael Acceptors by Halogen-Bond Donors

Extending earlier studies on iodine catalysis, experimental investigations show that various halogen-bond donors can also be employed to accelerate the Michael addition between trans -crotonophenone and indole. Solvent as well as counteranion effects have been analyzed, and kinetic and computational investigations provide additional insights into the mode of activation

Jemands Tod. Unica Zürn und Jacques Lacan. Anagramme, Subjekt- und Rechenmaschinen

Lutz H, Tyradellis D. Jemands Tod. Unica Zürn und Jacques Lacan. Anagramme, Subjekt- und Rechenmaschinen. In: Blümle C, von der Heiden A, eds. Blickzähmung und Augentäuschung. Zu Jacques Lacans Bildtheorie. 1st ed. Zürich; Berlin: Diaphanes; 2005: 145-163

Reaction Mechanism of Iodine-Catalyzed Michael Additions

Molecular iodine, an easy to handle solid, has been successfully employed as a catalyst in different organic transformation's for more than 100 years. Despite being active even in very small amounts, the origin of this remarkable catalytic effect is still unknown. Both a halogen bond mechanism as well as hidden Bronsted acid catalysis are frequently discussed as possible explanations. Our kinetic analyses reveal a reaction order of 1 in iodine, indicating that higher iodine species are not involved the rate-limiting transition state. Our experimental investigations rifle out hidden Bronsted acid catalysis by partial deconiposition of I-2 to HI and suggest a halogeri bond activation instead. Finally, molecular iodine turned out to be a similar if not superior,catalyst for Michael additions compared with typical Lewis acids

Are bis(pyridine)iodine(i) complexes applicable for asymmetric halogenation?

Enantiopure halogenated molecules are of tremendous importance as synthetic intermediates in the construction of pharmaceuticals, fragrances, flavours, natural products, pesticides, and functional materials. Enantioselective halofunctionalizations remain poorly understood and generally applicable procedures are lacking. The applicability of chiral trans-chelating bis(pyridine)iodine(I) complexes in the development of substrate independent, catalytic enantioselective halofunctionalization has been explored herein. Six novel chiral bidentate pyridine donor ligands have been designed, routes for their synthesis developed and their [N–I–N]+-type halogen bond complexes studied by 15N NMR and DFT. The chiral complexes encompassing a halogen bond stabilized iodenium ion are shown to be capable of efficient iodenium transfer to alkenes; however, without enantioselectivity. The lack of stereoselectivity is shown to originate from the availability of multiple ligand conformations of comparable energies and an insufficient steric influence by the chiral ligand. Substrate preorganization by the chiral catalyst appears a necessity for enantioselective halofunctionalization