Notes

L influx syndromes: What's brand-new?: M say syndromes.
A voltammetric study of a series of alkyl and aryl S-glucosides unveiled the reactivity patterns of alkyl S-glucosides toward anodic oxidation and found noteworthy differences with the trends followed by aryl derivatives. The oxidation potential of alkyl S-glucosides, estimated herein from square-wave voltammetry peak potentials (Ep), depends on the steric properties of the aglycone. Glucosides substituted with bulky groups exhibit Ep values at voltages more positive than the values of those carrying small aglycones. This relationship, observed in all analyzed alkyl series, is evidenced by good linear correlations between Ep and Taft's steric parameters (ES) of the respective alkyl substituents. Moreover, the role of the aglycone's steric properties as a primary reactivity modulator is backed by poor correlations between Ep and the radical stabilization energies (RSEs) of the aglycone-derived thiyl radicals (RS•). In contrast, aryl glucosides' Ep values exhibit excellent correlations with the aryl substituents' Hammett parameters (σ+) and the ArS• RSEs, evidencing the inherent stability of the reactive radical intermediate as the primary factor controlling aryl glucoside's electrochemical reactivity. The reactivity differences between alkyl and aryl S-glucosides also extend to the protective group's effect on Ep. Alkyl S-glucosides' reactivity proved to be more sensitive to protective group exchange.The therapeutic properties of Curcuma (ginger and turmeric's family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from Curcuma phaeocaulis been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework. Prompted by the promising biological profile of phaeocaulisin A and by the absence of a synthetic route for its provision, we have implemented the first enantioselective total synthesis of phaeocaulisin A in 17 steps with 2% overall yield. Our route design builds on the identification of an enantioenriched lactone intermediate, tailored with both a ketone moiety and a conjugated alkene system. Taking advantage of the umpolung carbonyl-olefin coupling reactivity enabled by the archetypal single-electron transfer (SET) reductant samarium diiodide (SmI2), the lactone intermediate was submitted to two sequential SmI2-mediated cyclizations to stereoselectively construct the polycyclic core of the natural product. Crucially, by exploiting the innate inner-sphere nature of carbonyl reduction using SmI2, we have used a steric blocking strategy to render sites SET-unreceptive and thus achieve chemoselective reduction in a complex substrate. Our asymmetric route enabled elucidation of the naturally occurring isomer of phaeocaulisin A and provides a synthetic platform to access other guaiane-type sesquiterpenes from C. phaeocaulis─as well as their synthetic derivatives─for medicinal chemistry and drug design.The lead optimization stage of a drug discovery program generally involves the design, synthesis, and assaying of hundreds to thousands of compounds. The design phase is usually carried out via traditional medicinal chemistry approaches and/or structure-based drug design (SBDD) when suitable structural information is available. Two of the major limitations of this approach are (1) difficulty in rapidly designing potent molecules that adhere to myriad project criteria, or the multiparameter optimization (MPO) problem, and (2) the relatively small number of molecules explored compared to the vast size of chemical space. To address these limitations, we have developed AutoDesigner, a de novo design algorithm. AutoDesigner employs a cloud-native, multistage search algorithm to carry out successive rounds of chemical space exploration and filtering. Millions to billions of virtual molecules are explored and optimized while adhering to a customizable set of project criteria such as physicochemical properties and pot chemical matter within the constraints of a given drug discovery lead optimization campaign.The restriction on legacy perfluoroalkyl substances (PFASs) has led to increasing application and contamination of their precursors and novel alternatives. However, the indirect contribution from precursors has not been well characterized. In this study, 24 PFASs were measured in the paired human blood and urine from general volunteers (n = 20), as well as their corresponding exposure matrices (7 day duplicate diet, drinking water and dust). Perfluorooctanoic acid (PFOA) was predominant, followed by 62 chlorinated polyfluoroalkyl ether sulfonate (62 Cl-PFESA), contributing 21.6-47.0 and 6.6-20.0% of the total concentrations, respectively. Total oxidable precursor (TOP) assay and isomeric analysis coupled with a toxicokinetic model suggested that around 19% of perfluorooctane sulfonate (PFOS) in human was contributed by its precursors. The strong correlation between the estimated daily intake (EDI) and human blood concentration for 62 Cl-PFESA suggested that it was mainly contributed by direct exposure. The bioavailability of 62 Cl-PFESA in the food matrices was estimated as 18.6% by comparing the estimated and measured blood concentrations, implying that human exposure might be overestimated if the bioavailability of PFASs in food was not considered. Assuming that they had a similar bioavailability, it was estimated that ca. 20% of PFOS body burden was from indirect exposure to its precursors, which was supported by TOP assay.The real-time and in situ monitoring of the synthesis of nanomaterials (NMs) remains a challenging task, which is of pivotal importance by assisting fundamental studies (e.g., synthesis kinetics and colloidal phenomena) and providing optimized quality control. In fact, the lack of reproducibility in the synthesis of NMs is a bottleneck against the translation of nanotechnologies into the market toward daily practice. Here, we address an impedimetric millifluidic sensor with data processing by machine learning (ML) as a sensing platform to monitor silica nanoparticles (SiO2NPs) over a 24 h synthesis from a single measurement. The SiO2NPs were selected as a model NM because of their extensive applications. Impressively, simple ML-fitted descriptors were capable of overcoming interferences derived from SiO2NP adsorption over the signals of polarizable Au interdigitate electrodes to assure the determination of the size and concentration of nanoparticles over synthesis while meeting the trade-off between accuracy and speed/simplicity of computation. The root-mean-square errors were calculated as ∼2.0 nm (size) and 2.6 × 1010 nanoparticles mL-1 (concentration). Further, the robustness of the ML size descriptor was successfully challenged in data obtained along independent syntheses using different devices, with the global average accuracy being 103.7 ± 1.9%. Dynasore nmr Our work advances the developments required to transform a closed flow system basically encompassing the reactional flask and an impedimetric sensor into a scalable and user-friendly platform to assess the in situ synthesis of SiO2NPs. Since the sensor presents a universal response principle, the method is expected to enable the monitoring of other NMs. Such a platform may help to pave the way for translating "sense-act" systems into practice use in nanotechnology.Recent clinical trials have revealed that the chimeric peptide hormones simultaneously activating glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) demonstrate superior efficacy in glycemic control and body weight reduction, better than those activating the GLP-1R alone. However, the linear peptide-based GLP-1R/GIPR dual agonists are susceptible to proteolytic cleavage by common digestive enzymes present in the gastrointestinal tract and thus not suitable for oral administration. Here, we report the design and synthesis of biaryl-stapled peptides, with and without fatty diacid attachment, that showed potent GLP-1R/GIPR dual agonist activities. Compared to a linear peptide dual agonist and semaglutide, the biaryl-stapled peptides displayed drastically improved proteolytic stability against the common digestive enzymes. Furthermore, two stapled peptides showed excellent efficacy in an oral glucose tolerance test in mice, owing to their potent receptor activity in vitro and good pharmacokinetics exposure upon subcutaneous injection. By exploring a more comprehensive set of biaryl staplers, we expect that this stapling method could facilitate the design of the stapled peptide-based dual agonists suitable for oral administration.Silicon oxide (SiOx) has outstanding capacity and stable lithium-ion uptake/removal electrochemistry as a lithium-ion anode material; however, its practical massive commercialization is encumbered by unavoidable challenges, such as dynamic volume changes during cycling and inherently inferior ionic conductivities. Recent literature has offered a consensus that binders play a critical role in affecting the electrochemical performance of Si-based electrodes. Herein, we report an aqueous binder, γ-polyglutamic acid cross-linked by epichlorohydrin (PGA-ECH), that guarantees enhanced properties for SiOx anodes to implement long-term cycling stability. The abundant amide, carboxyl, and hydroxyl groups in the binder structure form strong interactions with the SiOx surface, which contribute strong interfacial adhesion. The robust covalent interactions and strong supramolecular interactions in the binder ensure mechanical strength and elasticity. Additionally, the interactions between lithium ions and oxygen (nitrogen) atoms of carboxylate (peptide) bonds, which serve as a Lewis base, facilitate the diffusion of lithium ions. A SiOx anode using this PGA-ECH binder exhibits an impressive initial discharge capacity of 1962 mA h g-1 and maintains a high capacity of 900 mA h g-1 after 500 cycles at 500 mA g-1. Meanwhile, the assembled SiOx||LiNi0.6Co0.2MnO0.2 full cell shows a reversible capacity of 155 mA g-1 and displays 73% capacity retention after 100 cycles.Recently, Cu2AgBiI6 semiconductor has been investigated due to the high absorption coefficient, direct bandgap, and low exciton binding energy, which are promising for eco-friendly photoelectric devices. Herein, pyridine is introduced as solvent additive to completely dissolve the solutes and form clear Cu2AgBiI6 precursor solution, which results in high-quality films and may provide a general approach for high-quality film growth of other bismuth-based metal halide semiconductors. In addition, the electronic structure of Cu2AgBiI6 has been demonstrated for the first time and shows an intrinsically weak n-type semiconductor. Furthermore, phenethylammonium iodide for surface passivation significantly improves the film quality, slightly n-dopes the material, and shifts up the band level. Finally, the photovoltaics and photodetector performance for n-i-p planar heterojunction devices have been investigated. The efficiency is up to 1%, highest for Cu2AgBiI6 solar cells and comparable with other lead-free bismuth based metal halide solar cells.
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