Carbazole-based polymers having a high refractive index of above 1.70 and desirable Abbe number are reported here. These polymers were prepared by the photoclick thiol-ene reaction of two types of allyl-containing carbazole monomers with thiophenol or mercaptans. Among the monomers, those possessing allyl substituents at positions 2 and 7 give the polymers with higher refractive index and satisfactory Abbe number. The polymers also display good thermal and mechanical properties. Moreover, the films prepared from these polymers exhibit good surface roughness. This is a first example regarding the high refractive index polymers derived from allyl-containing carbazoles, and the results suggest the polymers have a potential application as the optical materials in the industry.

Deracemization of C(sp3)-H arylated carbonyl compounds faces limitations in terms of substrate scope. Through the photoactivation of the aryl group and the stereocontrol of the generated arene radical cation via asymmetric ion-pairing catalysis, we are able to achieve deracemization of carbonyl compounds arylated at both enolizable and unenolizable stereocenters. A diverse range of alpha-, beta-, and gamma-aryl ketones and esters, including natural products and medicinal derivatives, can be effectively converted into their enantiomers with high enantioselectivity. Mechanistic investigations through combined experimental and computational studies suggest that the reaction involves single-electron oxidation of electron-rich aryl groups, followed by a kinetic resolution of the resulting radical cation intermediates by the chiral phosphate anion. Deprotonation is identified as the stereodetermining step, while stereoselective back electron transfer and triplet-state quenching of 3 Mes-Acr1 +* may also affect the enantioselectivity at the photostationary state.

Pathological stress can lead to failure in the translocation of mitochondrial proteins, resulting in accumulation of unimported proteins within the cytosol and upregulation of proteasome for their quality control. Malfunction or delay in protein clearance causes dysregulation of mitochondrial protein homeostasis, cellular toxicity, and diseases. Ubiquilins (UBQLNs) are known to serve as chaperone, which associates with unimported mitochondrial membrane protein precursors, and facilitates their proteasomal degradation. However, how UBQLN-engaged proteins are ubiquitinated and efficiently targeted to the proteasome are poorly understood. Here, using mitochondrial membrane protein ATP5G1 (ATP synthase F(0) complex subunit C1) as a model substrate, we report that E3 ubiquitin ligase RNF126 interacts with substrate-engaged UBQLN1, thereby promoting ubiquitination and degradation of unimported proteins during mitochondrial stress. We find that UBQLN1's ubiquitin-associated domain recruits RNF126 when its middle domain binds to unimported protein substrate. Recombinant RNF126 forms ternary complex with UBQLN1 and ATP5G1 precursor in vitro and catalyzes ubiquitination of UBQLN1-bound ATP5G1. Without RNF126, proteasomal degradation of ATP5G1 was compromised. These results explain how RNF126 and UBQLNs interplay to ensure specific quality control of unimported mitochondrial membrane proteins under pathophysiological conditions.

Ketene was identified as an intermediate in syngas-to-olefin (STO) conversion catalyzed by metal oxide-zeolite composites, which sparked a hot debate regarding its formation mechanism and catalytic roles. Here, we employed large-scale atomic simulations using global neural network potentials to explore the STO reaction pathways and microkinetic simulations to couple the reaction kinetics in ZnCrOx|SAPO-34 composite sites. Our results demonstrate that the majority of ketene (86.1%) originates from the methanol carbonylation-to-ketene route via nearby zeolite acidic sites, where methanol is produced through conventional syngas-to-methanol conversion on the Zn3Cr3O8 (0001) surface, while the minority of ketene (13.9%) arises from a direct CHO*-CO* coupling pathway (CHO* + CO* + H* -> CHOCO* + H* -> CH2CO + O*) on Zn3Cr3O8. The presence of the ketene pathway significantly alters the catalytic performance in the zeolite, as methanol carbonylation to ketene is kinetically more efficient in competing with conventional methanol-to-olefins (MTO) conversion and thus predominantly drives the product to ethene. Based on our microkinetic simulation, it is the methanol carbonylation activity in the zeolite that dictates the performance of STO catalysts.

Living crystallization-driven self-assembly (CDSA) has been regarded as a powerful strategy to generate pi-conjugated-polymer-based nanofibers (CPNFs). However, the limited morphological stability and surface tailorability of the resulting CPNFs hinder board applications. Development of highly efficient and facile strategies endowing CPNFs with morphological stability and surface tailorability is, thus, highly desirable. Herein, we report a versatile and facile platform to create uniform CPNFs with controlled length/composition, excellent stability, and surface tailorability by combining living CDSA with the nitrile N-oxide (NNO)-based click reaction. We prepare uniform CPNFs of controlled length/composition containing a PNAAM (poly(N-allyl acrylamide)) corona and an OPV5- (OPV = oligo(p-phenylenevinylene)) or OPE4-DPP-OPE4-based (OPE = oligo(p-phenylene ethynylene), DPP = diketopyrrolopyrrole) core by living CDSA. It is found that NNO units selectively react with alkenes (vinyls) of the PNAAM segment, leaving the chemical structure of the alkene- and alkyne-containing OPV5- and OPE4-DPP-OPE4 intact. 1,3-Dipolar cycloaddition of nitrile N-oxide (NNO) with alkenes of PNAAM segments is then employed to make the shell of the CPNFs cross-link at ambient temperature without the usage of any catalyst and production of any byproduct; the resulting CPNFs exhibit excellent morphological stability in organic solvents and at elevated temperature. By the cycloadditions, additional fluorescent dyes also are introduced into the corona-forming PNAAM segment, which allows the preparation of uniform continuous and segmented CPNFs with high fluorescence by the living CDSA. Additionally, the resulting CPNFs show limited cytotoxicity against both H1299 and HepG2 cell lines, even if the micelles can be uptaken by H1299 cells. This works not only broadens the application scope of NNO-based click ligation but also provides a versatile platform to create CPNFs of varying functionalities and high stability by combining living CDSA and NNO-based click reaction.

An efficient method for the synthesis of [18F]-difluoromethylated alkanes by the combination of [18F]radio-fluoride with monofluoroalkyl triflates has been developed. This method uses [18F]KF/K2.2.2 as the fluorine source. It features synthetic simplicity without tedious precursor preparation, high RCC and RCY, good functional group tolerance, and is silver salt-free, providing potential for developing new PET agents.

Selective functionalization of ubiquitous C-H bonds in organic molecules provides a straightforward and efficient approach to construct complex molecules with fewer synthetic steps and high atom economy, thus promoting more sustainable and economical chemical synthesis. A formidable challenge in the field is to increase the turnover numbers (TONs) for catalytic C-H functionalization reactions reported in the literature (generally<10,000) to="" reasonably="" high="" levels="" reduce="" the="" cost="" of="" reaction.="" another="" challenge="" is="" selective="" functionalization="" less="" reactive="" primary="" c="">

Visible light-induced perfluoroalkylation reaction of 3-substituted indoles using Na2-Eosin Y as photoredox catalysis was achieved under mild conditions to give a series of C2-perfluoroalkylated indoles in moderate to good yields. Under similar conditions, both C3 and C4 perfluoroalkylation reactions of 2-substituted indoles occurred to produce two regioisomers. The reaction of unsubstituted indole gave the C2 and C3 perfluoroalkylation products. A possible pathway was proposed based on the experimental results.

Peroxisomes are integral metabolic organelles involved in both catabolic and anabolic processes in humans, with defects linked to diseases. The functions of peroxisomes are regulated at transcriptional, translational, and posttranslational levels. In this study, we employed the CRISPR/Cas9-based screening of a ubiquitin ligase library to identify regulators of human peroxisomes. We discovered that ZBTB17 (MIZ1) plays a role in regulating the import of proteins into peroxisomes. Independent of its ubiquitin ligase activity, ZBTB17/MIZ1 operates as a transcription factor to modulate the expression of key importer PEX13, influencing the localization of peroxisomal enzymes. Furthermore, metabolomic profiling reveals that knockdown of ZBTB17 or PEX13 results in similar metabolic alterations, with downregulated purine synthesis. Collectively, we identify ZBTB17 as a key regulator of peroxisomal protein import, thereby affecting peroxisomal function and nucleotide metabolism. Our findings provide insights into the multifaceted regulation of peroxisomes in complex human cells and shed light on the molecular mechanisms underlying ZBTB17's role as a transcriptional regulator.

Oncogenic mutations in EGFR often result in EGF-independent constitutive activation and aberrant trafficking and are associated with several human malignancies, including non-small cell lung cancer. A major consequence of EGFR mutations is the activation of the mechanistic target of rapamycin complex 1 (mTORC1), which requires EGFR kinase activity and downstream PI3K/AKT signaling, resulting in increased cell proliferation. However, recent studies have elucidated kinase-independent roles of EGFR in cell survival and cancer progression. Here, we report a cis mTORC1 activation function of EGFR that is independent of its kinase activity. Our results reveal that lysosomal localization of EGFR is critical to mTORC1 activation, where EGFR physically binds Rheb, acting as a guanine exchange factor (GEF) for Rheb, with its Glu804 serving as a potential glutamic finger. Genetic knock-in of EGFR-E804K in cells reduces the level of GTP-bound Rheb, and significantly suppresses mTORC1 activation, cell proliferation and tumor growth. Different tyrosine kinase inhibitors exhibit distinct effects on EGFR-induced mTORC1 activation, with afatinib, which additionally blocks EGFR's GEF activity, causing a much greater suppression of mTORC1 activation and cell growth, and erlotinib, which targets only kinase activity, resulting in only a slight decrease. Moreover, a novel small molecule, BIEGi-1, was designed to target both the Rheb-GEF and kinase activities of EGFR, and shows a strong inhibitory effect on the viability of cells harboring EGFR mutants. These findings unveil a fundamental event in cell growth and suggest a promising strategy against cancers with EGFR mutations.

At the same time that our capabilities to synthesize open-shell carbon-based materials are rapidly growing with the development of on-surface synthesis under vacuum conditions, interest in pi-magnetism is rising due to its excellent prospects for potential applications. As a result, increasing efforts are being focused on the detailed understanding of open-shell carbon nanostructures and all of the parameters that determine their spin densities and magnetic ground states. Here we present a facile route to synthesize different open-shell acene derivatives with closely related structures by the addition of functional groups. A systematic comparison allows us to draw conclusions on the role of the functional groups and their number and distribution, as well as on the role of the radical state delocalization in relation with the presence or absence of charge transfer at interfaces, which consequently affects the molecule's pi-magnetism.