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Purpose: Exercise‐associated hyponatremia (EAH) is common in ultra‐endurance events and severe cases are more common in females. The purpose of this paper is to compare the clinical presentation of EAH between male and female triathletes in ultra‐endurance competitions. Methods: Medical records with sodium concentrations (n = 3138) from the IRONMAN® World Championships over the timeframe of 1989–2019 were reviewed for both male (n = 2253) and female (n = 885) competitors. Logistic regression was used to explore the relationships between sex, sodium concentration, and various clinical presentations. Results: When comparing male and female triathletes, clinical variables found to have a different relationship with sodium concentration include altered mental status (inversely related in males and not related in females), abdominal pain, muscle cramps, hypotension, and tachycardia (directly related in males and not related in females), and vomiting and hypokalemia (not related in males and inversely related in females). Overall, males lost significantly more weight than females, and notably, approximately half of all athletes were dehydrated and lost weight. Conclusions: Altered mental status, vomiting, abdominal pain, muscle cramps, hypotension, tachycardia, and hyperkalemia appear to present differently between sexes when comparing hyponatremic to eunatremic athletes. Although overhydration is the most common etiology of hypervolemic hyponatremia, hypovolemic hyponatremia comprises a significant amount of hyponatremic triathletes. Further understanding of how EAH presents helps athletes and medical professionals identify it early and prevent life‐threatening complications. [ABSTRACT FROM AUTHOR]

The critical micelle concentration is an important property of supramolecular detergents. Two dynamic light scattering approaches have been developed for critical micelle concentration analysis, i. e., concentration-dependent light scattering intensity analysis and diffusion coefficient analysis. Their utility as complementary tools for a reproducible determination of critical micelle concentration remains to be clarified. Herein, we address the question which of the two approaches is more suitable for obtaining reproducible critical micelle concentration values. We systematically compare both approaches in context with common detergent classes and benchmark utility by means of literature values. Our results show that the diffusion coefficient analysis delivers reproducible critical micelle concentration values in aqueous solutions. Our findings outline a roadmap to guide the critical micelle concentration analysis of detergents by dynamic light scattering in the future., (© 2024 The Author(s). ChemPlusChem published by Wiley-VCH GmbH.)

The development of the most comprehensive universal calibration of molar mass dependences will be presented. For the first time, diffusion-ordered spectroscopy (DOSY) can now provide structure-, solvent-, and temperature-independent molar mass determinations for both small and large molecules. This fundamental theoretical approach provides only one single function which could perfectly describe all molar mass dependences. The new development using DOSY was tested on 477 diffusion coefficients representing altogether 56 molar mass dependences of 30 small molecules in 7 solvents, 5 different polymers in 10 solvents, and 11 temperature dependences of 2 polymers in 2 solvents, respectively. These samples cover a very large range of molar masses varying between 70 g/mol until 1 200 000 g/mol. The derived equation for the molar masses delivered a very good accuracy for all samples and might be one of the best tools for molar mass determinations.

The aim of this study was to introduce a powerful coupling of Liquid Adsorption Chromatography (LAC) and Diffusion-Ordered Spectroscopy (DOSY) for comprehensive structure analysis. This new hyphenation approach facilitated the simultaneous separation of a polymer mixture and the determination of molar masses within a single 3D experiment. The online coupling of High-Performance Liquid Chromatography (HPLC) and two-dimensional DOSY-NMR will be called 3D-LAC-NMR-DOSY experiment. Our methodology enabled the chromatographic separation of analytes based on their chemical heterogeneity, and provided accurate molar masses of the analytes through 2D-DOSY. This new method was demonstrated on a polystyrene oligomer mixture. In this case, the oligostyrenes could be separated with LAC according to their tacticity and chain length in protonated acetonitrile as eluent and DOSY measurements provided the molar masses of each oligomer. In order to show the power of the 3D-LAC-NMR-DOSY method, the comparison to 2D-DOSY, 3D-DOSY and LAC-NMR was separately evaluated. Furthermore, the recently published solvent-independent molar mass calibration of diffusion coefficients was also successfully applied in our LAC-DOSY studies for molar mass predictions of the oligomers in acetonitrile. The predicted molar masses were in good agreement with the LAC-DOSY measurements and were verified by calibrations of diffusion coefficients and mass spectrometry. Finally, this pioneering 3D technique offers a powerful new tool for advancing structure analysis and enhancing our understanding of complex systems such as oligostyrenes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Interpreting NMR experiments benefits from first-principles predictions of chemical shifts. Reaching the accuracy limit of theory is relevant for unambiguous structural analysis and dissecting theoretical approximations. Since accurate chemical shift measurements are based on using internal reference compounds such as trimethylsilylpropanesulfonate (DSS), a detailed comparison of experimental with theoretical data requires simultaneous consideration of both target and reference species ensembles in the same solvent environment. Here we show that ab initio molecular dynamics simulations to generate liquid-state ensembles of target and reference compounds, including explicitly their short-range solvation environments and combined with quantum-mechanical solvation models, allows for predicting highly accurate 1 H (∼0.1-0.5 ppm) and aliphatic 13 C (∼1.5 ppm) chemical shifts for aqueous solutions of the model compounds trimethylamine N -oxide (TMAO) and N -methylacetamide (NMA), referenced to DSS without any system-specific adjustments. This encompasses the two peptide bond conformations of NMA identified by NMR. The results are used to derive a general-purpose guideline set for predictive NMR chemical shift calculations of NMA in the liquid state and to identify artifacts of force field models. Accurate predictions are only obtained if a sufficient number of explicit water molecules is included in the quantum-mechanical calculations, disproving a purely electrostatic model of the solvent effect on chemical shifts.

It will be shown how diffusion-ordered spectroscopy (DOSY) can produce a universal calibration of molar mass dependences of polymers compared to size exclusion chromatography (SEC) or recently published DOSY methods. Whereas SEC can deliver only structure-independent universal calibrations for a particular solvent, DOSY was used for creating solvent-independent calibrations for a certain polymer. Now, we can demonstrate a universal calibration method that generates both a structure- and solvent-independent molar mass calibration. Only one mathematical function describes the structure- and solvent-independent calibrations for DOSY by implementing the Mark-Houwink approach. The derived equation is tested on polystyrene (PS), poly(ethylene oxide), and poly(methyl methacrylate) of different molar masses and in different solvents. Altogether, 94 diffusion coefficients representing 16 molar mass calibrations of the diffusion coefficients in 10 different solvents could be perfectly matched to one universal calibration function with an average deviation of just 2.5%. It was also found that the Mark-Houwink parameters calculated by DOSY are very close to the SEC data. In any case, this new approach is a very useful tool for the determination of molar masses and new Mark-Houwink parameters via DOSY.

Since its introduction in 2004, Knochel's so called Turbo-Grignard reagents revolutionized the usage of Grignard reagents. Through the simple addition of LiCl to a magnesium alkyl an outstanding increase in reactivity can be achieved. Though the exact composition of the reactive species remained mysterious, the reactive mixture itself is readily used not only in synthesis but also found its way into more distant fields like material science. To unravel this mystery, we combined single-crystal X-ray diffraction with in-solution NMR-spectroscopy and closed our investigations with quantum chemical calculations. Using such a variety of methods, we have gained insight into and an explanation for the extraordinary reactivity of this extremely convenient reagent by determining the structure of the first bimetallic reactive species [t-Bu 2 Mg ⋅ LiCl ⋅ 4 thf] with two tert-butyl anions at the magnesium center and incorporated lithium chloride., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Strong and weak halogen bonds (XBs) in discrete aggregates involving the same acceptor are addressed by experiments in solution and in the solid state. Unsubstituted and perfluorinated iodobenzenes act as halogen donors of tunable strength; in all cases, quinuclidine represents the acceptor. NMR titrations reliably identify the strong intermolecular interactions in solution, with experimental binding energies of approx. 7 kJ/mol. Interaction of the σ hole at the halogen donor iodine leads to a redshift in the symmetric C-I stretching vibration; this shift reflects the interaction energy in the halogen-bonded adducts and may be assessed by Raman spectroscopy in condensed phase even for weak XBs. An experimental picture of the electronic density for the XBs is achieved by high-resolution X-ray diffraction on suitable crystals. Quantum theory of atoms in molecules (QTAIM) analysis affords the electron densities and energy densities in the bond critical points of the halogen bonds and confirms stronger interaction for the shorter contacts. For the first time, the experimental electron density shows a significant effect on the atomic volumes and Bader charges of the quinuclidine N atoms, the halogen-bond acceptor: strong and weak XBs are reflected in the nature of their acceptor atom. Our experimental findings at the acceptor atom match the discussed effects of halogen bonding and thus the proposed concepts in XB activated organocatalysis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The syntheses of the racemic amino alcohol rac -N(CH 2 CMe 2 OH)(CMe 2 CH 2 OH)(CH 2 CHMeOH) ( L 22'1 * H 3 , 2 ) and its representative N(CH 2 CMe 2 OH)(CMe 2 CH 2 OH)(CH 2 C( R )HMeOH) ( L 22'1 R H 3 , 3 ) with the stereogenic carbon center being R -configured are reported. Also reported are the stannatranes L 22'1 * SnO t -Bu ( 4 ) L 22'1 R SnO t -Bu ( 6 ) and germatranes L 22'1 * GeOEt ( 5 ) and L 22'1 R GeOEt ( 7 ) as well as the trinuclear tin oxocluster [(μ 3 -O)(μ 3 -O- t -Bu){Sn L 22'1 R } 3 ] ( 8 ). NMR and IR spectroscopy, electrospray ionization mass spectrometry (ESI MS), and single crystal X-ray diffraction analysis characterize these compounds. Computational studies accompany the experimental work and help understand the diastereoselectivity observed in the course of the metallatrane syntheses.

Fragment-based drug discovery has played an important role in medicinal chemistry and pharmaceutical research. Despite numerous demonstrated successes, the limited diversity and overrepresentation of planar, sp 2 -rich structures in commercial libraries often hamper the full potential of this approach. Hence, the thorough design of screening libraries inevitably determines the probability for meaningful hits and subsequent structural elaboration. Against this background, we present the generation of an exclusive fragment library based on iterative entry nomination by a specifically designed computational workflow: "Fragtory". Following a pharmacophore diversity-driven approach, we used Fragtory in an interdisciplinary academic setting to guide both tailored synthesis efforts and the implementation of in-house compounds to build a curated 288-member library of sp 3 -enriched fragments. Subsequent NMR screens against a model protein and hit validation by protein crystallography led to the identification of structurally novel ligands that were further characterized by isothermal titration calorimetry, demonstrating the applicability of our experimental approach.

Benzoxazoles are important structural motifs in pharmaceutical drugs. Here, we present the heterologous production of 3-hydroxyanthranilate-derived benzoxazoles in the host bacterium Myxococcus xanthus following the expression of two genes from the nataxazole biosynthetic gene cluster of Streptomyces sp. Tü 6176. The M. xanthus expression strain achieved a benzoxazole titer of 114.6±7.4 mg L -1 upon precursor supplementation, which is superior to other bacterial production systems. Crosstalk between the heterologously expressed benzoxazole pathway and the endogenous myxochelin pathway led to the combinatorial biosynthesis of benzoxazoles featuring a 2,3-dihydroxybenzoic acid (2,3-DHBA) building block. Subsequent in vitro studies confirmed that this crosstalk is not only due to the availability of 2,3-DHBA in M. xanthus, rather, it is promoted by the adenylating enzyme MxcE from the myxochelin pathway, which contributes to the activation of aryl carboxylic acids and delivers them to benzoxazole biosynthesis., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

The natural product aurachin D is a farnesylated quinolone alkaloid, which is known to possess activity against the causative agent of malaria, Plasmodium spp. In this study, we show that aurachin D inhibits other parasitic protozoa as well. While aurachin D had only a modest effect on Trypanosoma brucei rhodesiense , two other trypanosomatids, T. cruzi and Leishmania donovani , were killed at low micromolar and nanomolar concentrations, respectively, in an in vitro assay. The determined IC 50 values of aurachin D were even lower than those of the reference drugs benznidazole and miltefosine. Due to these promising results, we set out to explore the impact of structural modifications on the bioactivity of this natural product. In order to generate aurachin D derivatives with varying substituents at the C-2, C-6 and C-7 position of the quinolone ring system, we resorted to whole-cell biotransformation using a recombinant Escherichia coli strain capable of aurachin-type prenylations. Quinolone precursor molecules featuring methyl, methoxy and halogen groups were fed to this E. coli strain, which converted the substrates into the desired analogs. None of the generated derivatives exhibited improved antiprotozoal properties in comparison to aurachin D. Obviously, the naturally occurring aurachin D features already a privileged structure, especially for the inhibition of the causative agent of visceral leishmaniasis.

Helicity is an archetypal structural motif of many biological systems and provides a basis for molecular recognition in DNA. Whilst artificial supramolecular hosts are often helical, the relationship between helicity and guest encapsulation is not well understood. We report a detailed study on a significantly coiled-up Pd 2 L 4 metallohelicate with an unusually wide azimuthal angle (∼176°). Through a combination of NMR spectroscopy, single-crystal X-ray diffraction, trapped ion mobility mass spectrometry and isothermal titration calorimetry we show that the coiled-up cage exhibits extremely tight anion binding ( K of up to 10 6 M -1 ) by virtue of a pronounced oblate/prolate cavity expansion, whereby the Pd-Pd separation decreases for mono-anionic guests of increasing size. Electronic structure calculations point toward strong dispersion forces contributing to these host-guest interactions. In the absence of a suitable guest, the helical cage exists in equilibrium with a well-defined mesocate isomer that possesses a distinct cavity environment afforded by a doubled Pd-Pd separation distance., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Bacteria of the genus Massilia represent an underexplored source of bioactive natural products. Here, we report the discovery of massinidine ( 1 ), a guanidine alkaloid with antiplasmodial activity, from these microbes. The unusual scaffold of massinidine is shown to originate from l-phenylalanine, acetate, and l-arginine. Massinidine biosynthesis genes were identified in the native producer and validated through heterologous expression in Myxococcus xanthus . Bioinformatic analyses indicate that the potential for massinidine biosynthesis is distributed in various proteobacteria.

Four new phenolic siderophores were isolated from the actinomycete Nocardia altamirensis along with the known natural product amamistatin B and a putative biosynthetic shunt product. The structures of all compounds were elucidated through 1D and 2D NMR analyses as well as mass spectrometry. The iron-chelating properties of the retrieved metabolites were evaluated in a chrome azurol S assay., (Copyright © 2022, Steinmetz et al.)

Lubricating greases based on urea thickeners are frequently used in high-performance applications since their invention in 1954. One property that has so far been neglected in the further development of these systems due to their low solubility and the resulting difficulty of analysis, is to better understand how the degree of polymerization affect such polyurea lubricating systems. In this work, we prepared three different oligo- or polyurea systemswith different degrees of polymerization (DP) and investigated the influence of DP on rheological and tribological properties. The results showed that the DP has an influence on the flow limit in rheology as well as on the extreme pressure (EP) and anti-wear (AW) properties as examined by tribology measurements. By optimizing the DP for a thickener system, comparable EP and AW properties can be achieved through the use of additives. The DP showed an increasing influence on the flow limit. This could reduce damage to rolling bearings due to lateral loading at rest. Therefore, modifying the DP of the polyurea systems shows similar effects as the addition of external additives. Overall, this would reduce the use of additives in industrial applications.

Fluorescent RNA aptamers have the potential to enable routine quantitation and localization of RNA molecules and serve as models for understanding biologically active aptamers. In recent years, several fluorescent aptamers have been selected and modified to improve their properties, revealing that small changes to the RNA or the ligands can modify significantly their fluorescent properties. Although structural biology approaches have revealed the bound, ground state of several fluorescent aptamers, characterization of low-abundance, excited states in these systems is crucial to understanding their folding pathways. Here we use pressure as an alternative variable to probe the suboptimal states of the Mango III aptamer with both fluorescence and NMR spectroscopy approaches. At moderate KCl concentrations, increasing pressure disrupted the G-quadruplex structure of the Mango III RNA and led to an intermediate with lower fluorescence. These observations indicate the existence of suboptimal RNA structural states that still bind the TO1-biotin fluorophore and moderately enhance fluorescence. At higher KCl concentration as well, the intermediate fluorescence state was populated at high pressure, but the G-quadruplex remained stable at high pressure, supporting the notion of parallel folding and/or binding pathways. These results demonstrate the usefulness of pressure for characterizing RNA folding intermediates., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)