Molecular basis for the stepwise and faithful maturation of the 20 proteasome.

The proteasome degrades most superfluous and damaged proteins, and its decline is associated with many diseases. As the proteolytic unit, the 20 proteasome is assembled from 28 subunits assisted by chaperones PAC1/2/3/4 and POMP; then, it undergoes the maturation process, in which the proteolytic sites are activated and the assembly chaperones are cleared. However, mechanisms governing the maturation remain elusive.

Regio- and Enantioselective Rhodium-Catalyzed Allylic Arylation of Racemic Allylic Carbonates with Arylboronic Acids.

Rhodium-catalyzed regio- and enantioselective allylic arylation of racemic alkyl- and aryl- substituted allylic carbonates with arylboronic acids using commercially available BIBOP ligand is reported. This reaction proceeds at room temperature without base or other additive to deliver allylic arylation products in excellent yields, regio- and enantioselectivity (up to 95% yield, >20:1 b/l, >99% ee). Rh/BIBOP is disclosed as an efficient catalytic system for allylic substitution reaction.

A Three-Component Reaction of Alkenyl Thianthrenium Salts, Cyclopropanols and Sulfur Dioxide.

A three-component reaction of alkenyl thianthrenium salts, cyclopropan-1-ols and DABCO·(SO) under catalyst- and additive-free conditions, is accomplished. This sulfonylation with the insertion of sulfur dioxide works efficiently under very mild conditions, leading to a wide range of 1-substituted vinyl sulfones in moderate to good yields. In this protocol, the scope generality of alkenyl thianthrenium salts and cyclopropyl alcohols is demonstrated.

Destabilization of Glycosyl Cation by an Electron-Withdrawing Substituent at C-5 Makes Sialylation Reaction More α-Stereoselective.

Comparison of the reactivity of sialyl chlorides and bromides based on -acetylneuraminic acid (Neu5Ac) and its deaminated analogue (KDN) in reactions with MeOH and -PrOH without a promoter revealed that the acetoxy group at C-5 in a molecule of a sialic acid glycosyl donor can destabilize the corresponding glycosyl cation making the S1-like reaction pathway unfavorable. A change to the S2-like reaction pathway ensures preferential formation of the α-glycoside.

A Facile Approach to Tetracyclic Indolines: Highly Diastereoselective [4+2] Annulation of Indoles with Bicyclic N-Substituted Cyclobutanes.

A new stereoselective [4+2] annulation method for constructing tetracyclic indolines by reacting indoles with bicyclic N-substituted cyclobutanes has been developed. Using Sc(OTf) as a catalyst, a series of tetracyclic indolines with four continued stereogenic carbon centers have been obtained in ≤86% yields as single diastereomers. This reaction offers an accessible way for the rapid construction of the core structures of biologically active natural products like paucidirinine, deethylibophyllidine, and ibophyllidine.

Ring-in-Ring Assembly Facilitates the Synthesis of a [12]Cycloparaphenylene ABC-Type [3]Catenane.

Cycloparaphenylenes (CPPs) represent a significant challenge for the synthesis of mechanically interlocked architectures, because they lack heteroatoms, which precludes traditional active and passive template methods. To circumvent this problem and explore the fundamental and functional properties of CPP rotaxanes and catenanes, researches have resorted to unusual non-covalent and even to labor-intensive covalent template approaches. Herein, we report a ring-in-ring non-covalent template strategy that makes use of the surprisingly strong non-covalent inclusion of crown ethers into suitably sized CPPs.

Cu-Catalyzed Relay Functionalization of Alkenes: Diverse Synthesis of Diazidated Quinazolinones and Polycyclic Imidazoles.

A Cu-catalyzed relay process for the preparation of diazidated quinazolinone and polycyclic imidazole derivatives in which readily available alkene-tethered substrates undergo an addition/cyclization/C(sp)-H functionalization of alkene sequences with high efficiency is described. Various functionalized N-heteropolycyclic compounds were readily prepared in good yields with a broad substrate scope. Moreover, the direct azidation of the α-C(sp)-H bond of the corresponding N-heterocycles has been demonstrated on the basis of mechanistic studies, which provide an alternative late-stage functionalization approach for the derivatization of N-heterocyclic scaffolds.

Copper-Catalyzed Intermolecular [2 + 2 + 2] Annulation of Diynes with Alkynes: Construction of Carbazoles.

Transition-metal-catalyzed [2 + 2 + 2] annulation of alkynes is an efficient pathway for the synthesis of aromatic compounds. However, most of the established methods require noble metal catalysts. Herein, we report a copper-catalyzed intermolecular [2 + 2 + 2] annulation of diynes with alkynes through vinyl cation intermediates, enabling the atom-economical preparation of biologically important carbazole skeletons.

Rational Modification of a Cross-Linker for Improved Flexible Protein Structure Modeling.

Chemical cross-linking/mass spectrometry (XL-MS) has emerged as a complementary tool for mapping interaction sites within protein networks as well as gaining moderate-resolution native structural insight with minimal interference. XL-MS technology mostly relies on chemoselective reactions (cross-linking) between protein residues and a linker. DSSO represents a versatile cross-linker for protein structure investigation and in-cell XL-MS.

Solvent-Dependent C(sp3)-CF3 Reductive Elimination from Neutral Four-Coordinate Cu(III) Complexes.

A solvent dependent C(sp3)-CF3 bond-forming reductive elimination from neutral four-coordinate Cu(III) complexes [(L)Cu(CF3)2(CH2CO2tBu)] (L = pyridine or its derivatives) is described. Reactions in less polar solvent ClCH2CH2Cl proceed via a concerted bond breaking/bond forming process along with the reorientation of the ligand, while reaction in polar solvent DMF occurs via a rate limiting ligand-dissociation, followed by C(sp3)-CF3 reductive elimination from the resulting three-coordinate intermediate. These mechanistic proposals are supported by kinetic studies that included ligand and temperature effects, as well as DFT calculations.

Sulfur functionalized diamondoid phosphines enable building nanocomposites interfacing sp-carbon and gold nanolayers.

Interfacing metal frameworks with carbon-based materials is attractive for the bottom-up construction of nanocomposite functional materials. The stepwise layering of difunctionalized diamantanes and gold metal from physical and chemical vapor deposition for the preparation of nanocomposites inverts the conventional preparation of metal-organic frameworks (MOFs) and self-assemblies, where the metal is introduced first, and this method delivers metal surfaces with modified properties originating from the sp-carbon core. However, appropriate diamondoid candidates for such an approach are rare.

The Elusive Ternary Intermediates of Chiral Phosphoric Acids in Ion Pair Catalysis─Structures, Conformations, and Aggregation.

In ion-pair catalysis, the last intermediate structures prior to the stereoselective transition states are of special importance for predictive models due to the high isomerization barrier between - and -substrate double bonds connecting ground and transition state energies. However, in prior experimental investigations of chiral phosphoric acids (CPA) solely the early intermediates could be investigated while the key intermediate remained elusive. In this study, the first experimental structural and conformational insights into ternary complexes with CPAs are presented using a special combination of low temperature and relaxation optimized N HSQC-NOESY NMR spectroscopy to enhance sensitivity.

Intermolecular 1,2-Difunctionalization of Nitriles via Redox Gold Catalysis: Synthesis of Benzoxazoles and Benzimidazoles.

The unprecedent gold-catalyzed intermolecular 1,2-difunctionalization of nitriles with aryl iodides via Au(I)/Au(III) redox catalysis has been developed, providing an expedient route to the synthesis of benzoxazoles and benzimidazoles with broad substrate scope and high functional compatibility. Mechanistic investigation reveals that the Au(III)-Ar species generated via oxidative addition of o-iodophenol to MeDalphosAu+, serves as a key intermediate. Particularly and this annulation is initiated by oxidative addition, rather than the nucleophilic attack of the phenol moiety in o-iodophenol towards the nitrile.

Impact of Boron Nitride on the Thermoelectric Properties and Service Stability of CuSe.

Improving the thermoelectric performance and service stability is essential for the effective use of cuprous selenide (CuSe). In this study, hexagonal boron nitride (h-BN) was incorporated into nano-CuSe, with the goal of enhancing thermoelectric performance and service stability. It was found that CuSe-0.

Structure and catalytic activity of the SAM-utilizing ribozyme SAMURI.

Ribozymes that catalyze site-specific RNA modification have recently gained increasing interest for their ability to mimic methyltransferase enzymes and for their application to install molecular tags. Recently, we reported SAMURI as a site-specific alkyltransferase ribozyme using S-adenosylmethionine (SAM) or a stabilized analog to transfer a methyl or propargyl group to N of an adenosine. Here, we report the crystal structures of SAMURI in the postcatalytic state.

Solid Lipid Nanoparticles Coated with Glucosylated poly(2-oxazoline)s: A Supramolecular Toolbox Approach.

Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline--2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule.

Breaking the cellular defense: the role of autophagy evasion in virulence.

Many pathogens have evolved sophisticated strategies to evade autophagy, a crucial cellular defense mechanism that typically targets and degrades invading microorganisms. By subverting or inhibiting autophagy, these pathogens can create a more favorable environment for their replication and survival within the host. For instance, some bacteria secrete factors that block autophagosome formation, while others might escape from autophagosomes before degradation.

The protein cargo of extracellular vesicles correlates with the epigenetic aging clock of exercise sensitive DNAmFitAge.

Extracellular vesicles (EVs) are implicated in inter-organ communication, which becomes particularly relevant during aging and exercise. DNA methylation-based aging clocks reflect lifestyle and environmental factors, while regular exercise is known to induce adaptive responses, including epigenetic adaptations. Twenty individuals with High-fitness (aged 57.

LEGO-Lipophosphonoxin membrane activity is enhanced by presence of phosphatidylethanolamine but hindered by outer membrane.

Finding effective antibiotics against multi-resistant strains of bacteria has been a challenging race. Linker-Evolved-Group-Optimized-Lipophosphonoxins (LEGO-LPPOs) are small modular synthetic antibacterial compounds targeting the cytoplasmic membrane. Here we focused on understanding the reasons for the variable efficacy of selected LEGO-LPPOs (LEGO-1, LEGO-2, LEGO-3, and LEGO-4) differing in hydrophobic and linker module structure and length.

BrCFCN for photocatalytic cyanodifluoromethylation.

Considering the unique electronic properties of the CF and the CN groups, the CFCN group has significant potential in drug and agrochemical development, as well as material sciences. However, incorporating a CFCN group remains a considerable challenge. In this work, we disclose a use of bromodifluoroacetonitrile (BrCFCN), a cost-effective and readily available reagent, as a radical source for cyanodifluoromethylation of alkyl alkenes, aryl alkenes, alkynes, and (hetero)arenes under photocatalytic conditions.

Interrupting Associative π-σ-π Isomerization Enables -Retentive Asymmetric Tsuji-Trost Reaction.

The asymmetric Tsuji-Trost reaction has been extensively studied due to its importance in establishing stereogenic centers, often adjacent to an -olefin moiety in organic molecules. The generally preferential formation of chiral -olefin products is believed to result from the thermodynamically more stable -π-allylpalladium intermediate. The rapid associative π-σ-π isomerization makes it challenging to synthesize chiral -olefin products via the transient -π-allylpalladium intermediate.

Dirhodium-Palladium Dual-Catalyzed [1 + 1 + 3] Annulation to Heterocycles Using Primary Amines or HO as the Heteroatom Sources.

The ever-increasing demand in chemical biology and medicinal research requires the development of new synthetic methods for the rapid construction of libraries of heterocycles from simple raw materials. In this context, the utilization of primary amines or HO as the simple - or -sources in the assembly of a heterocyclic ring skeleton is highly desirable from the viewpoint of atom- and step-economy. Herein, we describe a highly efficient three-component reaction of diazo, allylic diacetates, and commercially available anilines (or HO) to access structurally diverse pyrrolidine and tetrahydrofuran derivatives.

Solid-State Photoswitching of Hydrazones Based on Excited-State Intramolecular Proton Transfer.

The development of new photochromic systems is motivated by the possibility of controlling the properties and functions of materials with high spatial and temporal resolution in a reversible manner. While there are several classes of photoswitches operating in solution, the design of systems efficiently operating in the solid state remains highly challenging, mainly due to limitations related to confinement effects. Triaryl-hydrazones represent a relatively new subclass of bistable hydrazone photoswitches exhibiting efficient / photochromism in solution.