Muirlamont3186

A straightforward and modular sequence for the synthesis of substituted spirocyclic tetrahydrofurans is described. The strategy relies on a reductive cobalt-catalyzed three-component reaction between a cyclic ketone, an acrylate, and a vinylic bromide followed by an intramolecular iodoetherification of the resulting γ-hydroxyalkene. Some functional group interconversions allowed the preparation of more varied spirocyclic compounds.Terahertz vibrations are sensitive reporters of the structure and interactions of proteins. Ligand binding alters the nature and distribution of these collective vibrations. The ligand-induced changes in the terahertz protein vibrations contribute to the binding entropy and to the overall thermodynamic stability of the resultant protein-ligand complexes. Here, we have examined the response of the low-frequency (below 6 terahertz) collective vibrations of the calcium-loaded calmodulin (CaM) to binding to five different ligands, both in the presence and absence of water, using normal-mode analysis and molecular dynamics simulations. A comparison of the vibrational spectra of hydrated and dry systems reveals that protein-solvent interactions stiffen the terahertz protein vibrations and that these solvent-coupled collective vibrations contribute significantly to the hydration-sensitive variation in the vibrational entropy of CaM. In the absence of water, the low-frequency vibrations of CaM are stiffened by ligand binding. On the contrary, the number and the cumulative vibrational entropy of low-frequency vibrational modes (ω less then 200 cm-1) of the hydrated CaM are increased noticeably after binding to the peptides, indicating binding-induced softening of collective vibrations of the protein. Although the calculated and experimental binding affinities of the chosen complexes correlated reasonably well, no systematic correlation was observed between the protein vibrational entropy and the binding affinity. The results underscored the importance of the interplay of protein-ligand and solvent interactions in modulating the low-frequency vibrations of proteins.Interfacial photogenerated charge separation and transport have demonstrated great influence on photocatalytic performance. Herein, the composite photocatalysts of methylammonium lead iodide perovskite (MAPbI3) in TiO2 with a hollow multishell structure (HoMS) are designed and synthesized. The results indicate that the heterogeneous interface within the MAPbI3/Pt/TiO2-HoMS can help enhance the separation of photogenerated charges. HoMSs assembled with multiple shells can not only support large surfaces available for building a heterogeneous interface and photocatalytic reactions but also improve the light absorption capability of photocatalysts. Besides, the thin shell structure can also reduce the transmission distance of carriers so as to hinder charge recombination and improve charge utilization. As a result, samples of MAPbI3/Pt/triple-shelled TiO2 hollow structure displayed a H2 yield of 6856.2 μmol h-1 g-1 under visible light, which is greatly better than that of bare MAPbI3 (268.6 μmol h-1 g-1).Cytotoxic blistering agents such as sulfur mustard and nitrogen mustard (HN2) were synthesized for chemical warfare. Toxicity is due to reactive chloroethyl side chains that modify and damage cellular macromolecules including DNA and proteins. In response to DNA damage, cells initiate a DNA damage response directed at the recruitment and activation of repair-related proteins. A central mediator of the DNA damage response is p53, a protein that plays a critical role in regulating DNA repair. We found that HN2 causes cytosolic and nuclear accumulation of p53 in HaCaT keratinocytes; HN2 also induced post-translational modifications on p53 including S15 phosphorylation and K382 acetylation, which enhance p53 stability, promote DNA repair, and mediate cellular metabolic responses to stress. HN2 also cross-linked p53, forming dimers and high-molecular-weight protein complexes in the cells. Cross-linked multimers were also modified by K48-linked ubiquitination indicating that they are targets for proteasome degradation. HN2-induced modifications transiently suppressed the transcriptional activity of p53. Using recombinant human p53, HN2 alkylation was found to be concentration- and redox status-dependent. Dithiothreitol-reduced protein was more efficiently cross-linked indicating that p53 cysteine residues play a key role in protein modification. LC-MS/MS analysis revealed that HN2 directly alkylated p53 at C124, C135, C141, C176, C182, C275, C277, H115, H178, K132, and K139, forming both monoadducts and cross-links. The formation of intermolecular complexes was a consequence of HN2 cross-linked cysteine residues between two molecules of p53. Together, these data demonstrate that p53 is a molecular target for mustard vesicants. Modification of p53 likely mediates cellular responses to HN2 including DNA repair and cell survival contributing to vesicant-induced cytotoxicity.This work provided an interesting finding of lysine (Lys) control on skeletal muscle growth besides protein synthesis. According to the isobaric tag for relative and absolute quantitation and molecular docking analyses, we found both in in vivo skeletal muscle and in vitro muscle satellite cells (MuSCs) that the frizzled7 (FZD7) expression level was positively correlated with Lys levels and this was consistent with the activation of the Wnt/β-catenin pathway. On the other hand, FZD7 inhibition suppressed the Lys-rescued Wnt/β-catenin pathway, FZD7 knockdown caused cell proliferation, and Wnt/β-catenin pathway restrictions could not be compensated for by Lys or Wnt3a. Furthermore, the combination between Lys and recombinant pig frizzled7 (rpFZD7) protein was confirmed by isothermal titration calorimetry. This finding displayed concrete evidence that Lys is not only a molecular block of protein synthesis but is also a ligand for FZD7 to activate β-catenin to stimulate MuSCs in promoting skeletal muscle growth.Cucurbit[n]urils (Q[n]s or CB[n]s), as a classical of artificial organic macrocyclic hosts, were found to have excellent advantages in the fabricating of tunable and smart organic luminescent materials in aqueous media and the solid state with high emitting efficiency under the rigid pumpkin-shaped structure-derived macrocyclic-confinement effect in recent years. This review aims to give a systematically up-to-date overview of the Q[n]-based supramolecular organic luminescent emissions from the confined spaces triggered host-guest complexes, including the assembly fashions and the mechanisms of the macrocycle-based luminescent complexes, as well as their applications. Finally, challenges and outlook are provided. Since this class of Q[n]-based supramolecular organic luminescent emissions, which have essentially derived from the cavity-dependent confinement effect and the resulting assembly fashions, emerged only a few years ago, we hope this review will provide valuable information for the further development of macrocycle-based light-emitting materials and other related research fields.Reactions in microdroplets can be accelerated and can present unique chemistry compared to reactions in bulk solution. Here, we report the accelerated oxidation of aromatic sulfones to sulfonic acids in microdroplets under ambient conditions without the addition of acid, base, or catalyst. The experimental data suggest that the water radical cation, (H2O)+•, derived from traces of water in the solvent, is the oxidant. The substrate scope of the reaction indicates the need for a strong electron-donating group (e.g., p-hydroxyl) in the aromatic ring. An analogous oxidation is observed in an aromatic ketone with benzoic acid production. The shared mechanism is suggested to involve field-assisted ionization of water at the droplet/air interface, its reaction with the sulfone (M) to form the radical cation adduct, (M + H2O)+•, followed by 1,2-aryl migration and C-O cleavage. A remarkably high reaction rate acceleration (∼103) and regioselectivity (∼100-fold) characterize the reaction.Metal hydroxides catalyze organic transformations and photochemical processes and serve as precursors for the oxide layers of functional multicomponent devices. However, no general methods are available for the preparation of stable water-soluble complexes of metal hydroxide nanocrystals (NCs) that might be more effective in catalysis and serve as versatile precursors for the reproducible fabrication of multicomponent devices. We now report that InIII-substituted monodefect Wells-Dawson (WD) polyoxometalate (POM) cluster anions, [α2-P2W17O61InIIIOH)]8-, serve as ligands for stable, water-soluble complexes, 1, of platelike, predominantly cubic-phase (dzhalindite) In(OH)3 NCs that after optimization contain ca. 10% InOOH. CRT-0105446 manufacturer Images from cryogenic tranmsission electron microscopy reveal numerous WD ligands at the surfaces of platelike NCs, with average dimensions of 17 × 28 × 2 nm, each complexed by an average of ca. 450 InIII-substituted WD cluster anions and charge-balanced by 3600 Na+ countercations. Facilitated by the water solubility of 1, countercation exchange is used to stoichiometrically disperse ca. 1800 Cu2+ ions in an atomically homogeneous fashion around the surfaces of each NC core. The utility of this impregnation method is illustrated by using the ion-exchanged material as an electrocatalyst that reduces CO2 to CO 15 times faster per milligram of Cu than does K6Cu[P2CuII(H2O)W17O61] (control) alone. More generally, the findings point to POM complexation as a promising method for stabilizing and solubilizing reactive d-, p-, and f-block metal hydroxide NCs and for enabling their utilization as versatile components in the fabrication of functional multicomponent materials.Peptide and protein O-glycosylation can occur mostly on any serine or threonine and could generate several positional isomers, which may coelute during liquid chromatography (LC) separation, challenging their characterization. Ion mobility has emerged as a technique of interest to separate isomeric compounds. In the different ion mobility techniques, differential ion mobility (DMS) includes the particular interest to tune ion separation by the possible addition of an organic modifier. Different microflow liquid chromatography coupled to mass spectrometry (μLC-MS) workflows were investigated for the analysis of a set of four model peptides made of three isomeric glycopeptides and a corresponding nonglycosylated peptide using differential mobility spectrometry (DMS), collision induced dissociation (CID), and electron capture dissociation (ECD). Neither DMS nor LC provided sufficient separation of the three isomeric O-glycopeptides while the nonmodified one was clearly separated by LC. The hyphenation of LC with DMS led to differentiating the three glycopeptides, and further detection and characterization (ECD/CID) with a chimeric collision cell were achieved in a single LC run. The position of the modification was determined from ECD data, while CID data characterized the sugar through its distinctive oxoniums ions in the low mass range.Ribonuclease HI (RNHI) nonspecifically cleaves the RNA strand of RNADNA hybrid duplexes in a myriad of biological processes. Several RNHI homologs contain an extended domain, termed the handle region, which is critical to substrate binding. Nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations have suggested a kinetic model in which the handle region can exist in open (substrate-binding competent) or closed (substrate-binding incompetent) states in homologs containing arginine or lysine at position 88 (using sequence numbering of E. coli RNHI), while the handle region populates states intermediate between the open and closed conformers in homologs with asparagine at residue 88 [Stafford, K. A., et al., PLoS Comput. Biol. 2013, 9, 1-10]. NMR parameters characterizing handle region dynamics are highly correlated with enzymatic activity for RNHI homologs with two-state (open/closed) handle regions [Martin, J. A., et al., Biochemistry 2020, 59, 3201-3205]. The work presented herein shows that homologs containing asparagine 88 display distinct structural features compared with their counterparts containing arginine or lysine 88.