A novel hydrosulfonylation of alkenes using N-hydroxy sulfonamides as sulfonylating reagents has been achieved via visible light photoredox catalysis, featuring a broad substrate scope and high functional group compatibility. N-Hydroxysulfonamides were developed as a good sulfonyl radical source under visible-light catalysis and demonstrated great application potential in industrial and pharmaceutical synthesis.

Enantioselective electrophilic halogenation using organocatalysts has emerged as a powerful tool in asymmetric synthesis, yet its application has been largely concentrated on substrates bearing hydrogen bond donors. This prerequisite aligns with the design of conventional bifunctional catalysts, which operate through complementary hydrogen bond interactions with both the substrate and N-haloamide reagents. Chiral Buchwald-type ligands are useful monophosphine ligands, but their preparation mainly relies on kinetic resolution. Catalytic atroposelective halogenation of achiral Buchwald-type ligands would be an efficient strategy to prepare valuable C 1-symmetric axially chiral biaryl monophosphine ligands. However, Buchwald-type ligands lack hydrogen bond donors, making them incompatible with typical asymmetric halogenation systems. We hypothesized that an achiral halophenol additive could cross-assemble with a chiral phosphoric acid catalyst in situ, reconfiguring the active site from a electron donor/acceptor to an acceptor/acceptor bifunctional system. This strategy bridges the functional group mismatch between the catalyst and substrate. Herein, we report a catalytic desymmetrization of achiral Buchwald-type ligand derivatives via this cross-assembled catalysis. The resulting axially chiral halogenated ligands are amenable to late-stage diversification, providing facile access to a diverse array of chiral monodentate phosphine ligands for asymmetric catalysis.

Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin–activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus . Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.

Accurate modeling of low-κ dielectric materials is essential for advancing next-generation microelectronic devices. However, the inherent structural and chemical disorder in amorphous organosilicate glasses presents significant challenges for conventional molecular dynamics (MD) simulations, particularly when using empirical forcefields calibrated on crystalline phases. In this study, we explore the application of the Materials 3-body Graph Network (M3GNet), a machine learning interatomic potential, for high-fidelity modeling of amorphous organosilicate systems. By integrating M3GNet into extended MD workflows, we generated a chemically diverse set of low-κ organosilicate glass structures and computed their Young’s moduli. The resulting predictions of mechanical properties show excellent agreement with experimental data and outperform static deformation approaches based on density functional theory (DFT) and MD simulations using conventional force fields. These findings underscore the accuracy and transferability of M3GNet for disordered systems and demonstrate its utility in accelerating the structural and property prediction of amorphous low-κ materials.

THE BIGGER PICTURE The effective synthesis of innovative functional compounds frequently depends on the accessibility of chiral building blocks. In recent years, axially chiral biaryl compounds have attracted significant interest due to their diverse applications, and one notable example is circularly polarized luminescence materials. Asymmetric catalytic halofunctionalization has emerged as a key technique for the simultaneous introduction of chirality and halogen functionality. The halogen substituents produced can be readily modified to yield a variety of derivatives at a late stage, rendering halogenated chiral building blocks advantageous for multiple applications. Here, we report an approach that utilizes desymmetrizing asymmetric and regioselective bromination to generate C-N axially chiral N-arylcarbazoles. This process was enabled by a bifunctional catalyst, which was established by cross-assembling a chiral phosphate and an achiral pyridine through hydrogen and halogen bonding. The resulting bromo-carbazoles possess easily modifiable halogen substituents, which allow for the incorporation of additional chiral axes via cross-coupling reactions. Moreover, these axially chiral compounds, which feature coplanar arenes akin to the core structure of planar chiral [2.2]paracyclophanes, demonstrate high fluorescence quantum yields and commendable, satisfying circularly polarized luminescence performance. This research opens an avenue for the synthesis of planar chiral arene mimics, with potential applications in materials science.

Heterogeneous catalysis at the metal surface generally involves the transport of molecules through the interfacial water layer to access the surface, which is a rate-determining step at the nanoscale. In this study, taking the oxygen reduction reaction on a metal electrode in aqueous solution as an example, using accurate molecular dynamic simulations, we propose a novel long-range regulation strategy in which midinfrared stimulation (MIRS) with a frequency of approximately 1,000 cm-1 is applied to nonthermally induce the structural transition of interfacial water from an ordered to disordered state, facilitating the access of oxygen molecules to metal surfaces at room temperature and increasing the oxygen reduction activity 50-fold. Impressively, the theoretical prediction is confirmed by the experimental observation of a significant discharge voltage increase in zinc-air batteries under MIRS. This MIRS approach can be seamlessly integrated into existing strategies, offering a new approach for accelerating heterogeneous reactions and gas sensing within the interfacial water system.

The C—F bond transformation of gem-difluorinated cyclopropanes without cleavage of the highly strained C—C bond is an intractable challenge.The synthesis of cyclopropanone ketals via double defluorination of gem-difluorinated cyclo-propanes under transition-metal free and basic conditions has been developed.A broad range of gem-difluorinated cyclopro-panes and alcohols are amenable in present reaction to permit the synthesis of corresponding products in high yields.The reaction is elucidated to proceed via elimination and addition other than direct substitution based on the mechanistic studies.This transformation not only provides a new strategy for the construction of cyclopropanone ketals,but also reveals a new paradigm on C—F bond transformation without ring-opening ofgem-difluorinated cyclopropanes.

The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N–N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N–N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations.

We report herein an efficient NHC-catalyzed kinetic resolution of acyclic tertiary propargylic alcohols that provides them in high to excellent enantioselectivity. This is the first example of kinetic resolution realized by enantioselective acylation. The recovered enantioenriched alcohols can be facilely converted into other valuable compounds such as densely functionalized tertiary alcohols and carbmates in high yields and excellent stereopurity. Density functional theory calculations were performed to determine the reaction mechanism and to understand the origin of enantiodiscrimination.

The use of gem-difluorinated cyclopropanes (gem-DFCPs) as fluoroallyl surrogates under transition-metal catalysis has drawn considerable attention recently but such reactions are restricted to producing achiral or racemic mono-fluoroalkenes. Herein, we report the first enantioselective allylation of indoles under rhodium catalysis with gem-DFCPs. This reaction shows exceptional branched regioselectivity towards rhodium catalysis with gem-DFCPs, which provides an efficient route to enantioenriched fluoroallylated indoles with wide substrate scope and good functional group tolerance.

Three novel azatwistarenes 5a, 8, and 13 have been synthesized via the Povarov reaction and fully characterized. All of the enantiomers were separated using chiral high-performance liquid chromatography, and their optical properties were investigated through circular dichroism and circularly polarized luminescence spectra. In addition, such desired azatwistarenes have a positive response to acid in dichloromethane.

An efficient and highly enantioconvergent and diastereoselective ternary catalysis in a one-pot process is reported, which represents an integrated strategy for the synthesis of atropisomeric hydrazides with defined vicinal central and axial chirality from readily available racemic alpha-amino-ynones, azodicarboxylates, and Morita-Baylis-Hillman (MBH) carbonates. This method utilizes in situ-generated racemic pyrrolin-4-ones via hydroamination of racemic alpha-amino-ynones by AuCl catalysis as a novel and versatile C1 synthon, which engage commercially available azodicarboxylates to generate amination products in high yields and uniformly excellent enantioselectivities under the catalysis of a chiral phosphoric acid. Following amination, N-alkylation catalyzed by diastereoselective organocatalyst afforded axially chiral hydrazides with excellent diastereoselectivities (>98 : 2 dr). The synthetic utility of the amination products and axially chiral hydrazides was also demonstrated by their facile conversion to diverse molecules in high yields with excellent stereopurity. Density functional theory calculations were performed to understand the origin of diastereoselectivity.

Atomistic modeling of amorphous SiOC:H structures is crucial for understanding structure - property relationship and designing of new low - k materials. While a cubicgrid algorithm was previously developed to automatically construct amorphous SiOC:H structures, it required pre-treatment of the cubic grid to meet atomic valency and connectivity criteria. Additionally, the resulting structures suffered from persistent dangling bonds. In this paper, we introduce a novel unit -cell algorithm of generating amorphous SiOC:H structures. It takes the numbers of different types of silicon atoms (Q, T, D, M, and V) and the dimension of the supercell as input parameters. The algorithm ensures automatic handling of atomic coordinates, valency, connectivity, and cell periodicity by modeling the structures on the alpha-quartz unit cell. Throughout the process, these features are maintained by restricting the types of allowable structural modifications. Amorphous characteristics are introduced by randomly distributing various types of silicon atoms in the supercell. Our algorithm produces structures with amorphous traits, as shown by radial distribution function plots. To validate the effectiveness of the approach, we compare calculated properties of structures generated by the new algorithm to an experimental dataset of SiOC:H films. The good agreement between the two suggests that the new unit -cell algorithm is capable of generating realistic low - k amorphous SiOC:H structures.

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

In recent years, formal cycloaddition reactions involving bicyclo[1.1.0]butanes (BCBs) have furnished an array of innovative methodologies and strategies for the efficient synthesis of bicyclo[2.1.1]hexanes (BCHs). Most methods can be broadly classified into two main modes: the radical pathway and the two-electron pathway. This Synpacts article will summarize the recent advancements in Lewis acid catalyzed formal cycloaddition reactions involving BCBs with alkenes, dipolar molecules, and alkynes, spanning the period from 2022 to 2024. Additionally, we introduce the formal cycloaddition reaction of BCBs with ynamides, catalyzed by Sc(OTf)3, which has been recently developed by our group. This approach offers a novel and efficient method for the synthesis of polysubstituted 2-amino-bicyclo[2.1.1]hexenes.

In order to develop new composites composed of all carbon molecules and polynitrogen molecules, composites formed by a new all-carboatomic ring cyclo[18]carbon (C18) and a famous high energy molecule pentazole (N5H) with different proportions and sizes including N5H@C18, N5H@ 2 C18, 2 N5H@C18 and 2 N5H@ 2 C18 were designed. The intermolecular interactions, molecular and electronic structures, properties like conjugation effect and impact sensitivity, electrical conductivity and electrostatic sensitivity, recovery time, UV-Vis spectrum and IR spectrum were investigated theoretically. The results showed that N5H can be adsorbed inside the center of big C18 ring through the chemisorption. Intermolecular interactions in composites were mainly contributed by the dispersion interaction, but the electrostatic interaction also could not be neglected for 2 N5H@C18 and 2 N5H@ 2 C18 composites. The conjugation effect and ESP value in high positive region of N5H may be enhanced and decreased by C18, respectively, leading to better structural stability and lower impact sensitivity of composites than sole N5H. Due to the obviously decrease in energy GAP caused by C18, the electron transition ability and electrical conductivity of composites were greatly better than sole N5H, leading to lower electrostatic sensitivity and better safety performance markedly. Besides, the recovery time was very short, the difference in the UV-Vis and IR spectrum between sole N5H and composites was very obviously, showing the second function of C18 used as a new sensor for polynitrogen molecules like N5H.

High-entropy alloy catalysts with fascinating properties have inspired hot debate in renewable energy fields. Moreover, metal loaded hollow carbon nanostructures can boost the catalytic performance due to the void-confinement effect. In the paper, high-entropy alloy nanoparticles loaded hollow mesoporous carbon spheres (HMCS) with tailorable microenvironment effects were prepared for highly efficient hydrogenation of biomass-derived acetyl levulinate (LA) to produce the liquid fuel gamma-valerolactone (GVL). Moreover, the influence of curvature of hollow carbon shell on the electron-metal-carbon interaction (EMCI) as well as the enrichment and diffusion effects of high entropy alloys loaded hollow nanoreactor was investigated. The results revealed that nanoreactors with moderate curvature exhibited the most balanced reaction environment and enhanced electron-metal-carbon interaction (EMCI) effects, reducing the activation energy for acetyl levulinate conversion, resulting in high gamma-valerolactone yields. Furthermore, the high-entropy alloy’s abundant electronic characteristics established electron-rich regions on the metal surface, facilitating the hydrogenation of acetyl levulinate.

Spirocyclopentadienyl rhodium (SCpRh) complexes are powerful catalystsfor promoting asymmetric C-H functionalization reactions. However,the application of chiral SCp ligands is limited due to tedious syntheticprocedures and expensive starting materials. Herein, we have developeda series of chiral spiro ligands (BCSCp) with 6-7 steps fromcommercially available and cheap Bisphenol C. Their correspondingrhodium complexes have been prepared and successfully applied in enantioselectivearyl C-H addition to nitroalkenes, affording a series of C-Hadducts in up to 88% yield with up to 98% ee.

Nitroreductases (NTRs) constitute an important class of oxidoreductase enzymes that have evolved to metabolize nitro-containing compounds. Their unique characteristics have spurred an array of potential uses in medicinal chemistry, chemical biology, and bioengineering toward harnessing nitro caging groups and constructing NTR variants for niche applications. Inspired by how they carry out enzymatic reduction via a cascade of hydride transfer reactions, we sought to develop a synthetic small-molecule NTR system based on transfer hydrogenation mediated by transition metal complexes harnessing native cofactors. We report the first water-stable Ru-arene complex capable of selectively and fully reducing nitroaromatics into anilines in a biocompatible buffered aqueous environment using formate as the hydride source. We further demonstrated its application to activate nitro-caged sulfanilamide prodrug in formate-abundant bacteria, specifically pathogenic methicillin-resistant Staphylococcus aureus. This proof of concept paves the way for a new targeted antibacterial chemotherapeutic approach leveraging on redox-active metal complexes for prodrug activation via bioinspired nitroreduction.

Background and Aims:Nonsmall cell lung cancer accounts for over 85% of lung cancer incidences worldwide, and often has a poor prognosis. Proteasome inhibitors, such as bortezomib, have previously demonstrated evidence in preclinical and clinical models in the treatment of NSCLC both alone and as part of chemotherapeutic regimens. Methods:Five databases were searched from inception to February 2023 to identify published clinical trial data and ongoing clinical trials on the use of proteasome inhibitors in treatment of NSCLC with a comprehensive search strategy. Results:This review examines the clinical evidence from 21 completed and published phase I and II trials studying the use of bortezomib monotherapy and combination therapy in the treatment of NSCLC. Bortezomib/docetaxel combination resulted in longer median time-to-progression (TTP), median duration of response, median duration of disease control and median progression-free survival (PFS) than bortezomib monotherapy, with concurrent administration having greater 6-month PFS and median overall survival (OS) than sequential administration. Bortezomib/vorinostat with chemotherapy was well tolerated and effective. Bortezomib/gemcitabine/carboplatin, bortezomib/bevacizumab/carboplatin and bortezomib/paclitaxel/carboplatin combinations showed promising results and were of further investigational value. Conclusion:Bortezomib showed some clinical promise in combination therapy but not monotherapy. It also demonstrated a manageable side effect profile. Combination regimens are of further investigation value in Phase II trials.