The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Nanoporous graphene (NPG) materials are generated by removing internal degree-3 vertices from graphene and introducing nanopores with specific topological structures, which have been widely explored and exploited for applications in electronic devices, membranes, and energy storage. The inherent properties of NPGs, such as the band structures, field effect mobilities and topological properties, are crucially determined by the geometric structure of nanopores. On-surface synthesis is an emerging strategy to fabricate low-dimensional carbon nanostructures with atomic precision. In this review, we introduce the progress of on-surface synthesis of atomically precise NPGs, and classify NPGs from the aspects of element types, topological structures, pore shapes, and synthesis strategies. We aim to provide a comprehensive overview of the recent advancements, promoting interdisciplinary collaboration to further advance the synthesis and applications of NPGs. On-surface synthesis is a useful approach for the construction of nanoporous graphene materials, which are in turn of interest for various electronic applications. Here, the authors review the latest developments in the on-surface synthesis of atomically precise pristine and hetero-atom doped nanoporous graphene materials.

Receptor tyrosine kinases (RTKs) are cell surface receptors with kinase activity that play a crucial role in diverse cellular processes. Among the RTK family members, Human epidermal growth factor receptor 2 (HER2) and HER3 are particularly relevant to breast cancer. The review delves into the complexities of receptor tyrosine kinase interactions, resistance mechanisms, and the potential of anti-HER3 drugs, offering valuable insights into the clinical implications and future directions in this field of study. It assesses the potential of anti-HER3 drugs, such as pertuzumab, in overcoming resistance observed in HER2-positive breast cancer therapies. The review also explores the resistance mechanisms associated with various drugs, including trastuzumab, lapatinib, and PI3K inhibitors, providing insights into the intricate molecular processes underlying resistance development. The review concludes by emphasizing the necessity for further clinical trials to assess the efficacy of HER3 inhibitors and the potential of developing safe and effective anti-HER3 treatments to improve treatment outcomes for patients with HER2-positive breast cancer.

The synthesis of constrained 12-membered rings is notably difficult. The main challenges result from constraints during the linear peptide cyclization. Attempts to overcome constraints through excessive activation frequently cause peptidyl epimerization, while insufficient activation of the C-terminus hampers cyclization and promotes intermolecular oligomer formation. We present a beta-thiolactone framework that enables the synthesis of cyclo-tetrapeptides via direct aminolysis. This tactic utilizes a mechanism that restricts C-terminal carbonyl rotation while maintaining high reactivity, thereby enabling efficient head-to-tail amidation, reducing oligomerization, and preventing epimerization. A broad range of challenging cyclo-tetrapeptides ( > 20 examples) are synthesized in buffer and exhibits excellent tolerance toward nearly all proteinogenic amino acids. Previously unattainable macrocycles, such as cyclo-L-(Pro-Tyr-Pro-Val), have been produced and identified as mu-opioid receptor (MOR) agonists, with an EC50 value of 2.5 nM. Non-epimerizable direct aminolysis offers a practical solution for constrained peptide cyclization, and the discovery of MOR agonist activity highlights the importance of overcoming synthetic challenges for therapeutic development.

By virtue of the atom- and step-economy, utilization of simple arenes as a supplant of pre-prepared aryl metal species or aryl halides for the synthesis of arylated chiral molecules has attracted great attention from the synthetic community. While transition-metal-catalyzed enantioselective diarylation of tethered alkenes has been employed to prepare important chiral cyclic compounds, the direct use of simple arenes as aryl precursors is still underdeveloped, probably due to the difficulties in the effective control of the reactivity, site-selectivity and/or enantioselectivity. Herein we report an asymmetric Pd/Ag dual metal catalytic system for the non-directed, site- and enantioselective domino Heck/intermolecular C-H functionalization of arenes. Mechanistic studies showed that Pd and Ag act in cooperation in the catalysis and the chiral bisphosphine ligand plays a bifunctional role, i.e., assisting the silver species in the cleavage of the aryl C-H bond, while inducing the enantioselectivity on direct complexation with palladium. This method provides an efficient approach to the corresponding chiral oxindoles with good enantiomeric excesses from a broad scope of arenes, including fluoroarenes, heteroarenes and several complex products derived from medicines or natural products.

Within pharmaceutical research, ensuring the enantiomeric purity of chiral compounds is critical. Specifically, chiral amines are a crucial category of compounds, due to their extensive therapeutic uses. However, the enantiomeric analysis of these compounds, particularly those with significant steric hindrance, remains a challenge. To address this issue, our research introduces a novel chiral 19F-tagged NNO palladium pincer probe, strategically engineered with an open binding site to accommodate bulky amines. This probe facilitates the enantiodifferentiation of such amines, as evidenced by the distinct 19F NMR signals generated by the enantiomers. Moreover, our findings highlight the probe's applicability in the chiral discrimination of various psychoactive substances, underscoring its potential for the identification of illegal stimulant use and contributing to forensic investigations.

Accumulation of aggregated alpha-synuclein (alpha-syn) in Lewy bodies is the pathological hallmark of Parkinson's disease (PD). Genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism. The role of alpha-syn's lipid interactions in its function and aggregation is recognized, yet the specific lipids involved and how lipid metabolism issues trigger alpha-syn aggregation and neurodegeneration remain unclear. Here, we found that alpha-syn shows a preference for binding to lysophospholipids (LPLs), particularly targeting lysophosphatidylcholine (LPC) without relying on electrostatic interactions. LPC is capable of maintaining alpha-syn in a compact conformation, significantly reducing its propensity to aggregate both in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs is associated with an increase in alpha-syn accumulation. Our work underscores the critical role of LPLs in preserving the natural conformation of alpha-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and alpha-syn aggregation in PD.

Solar-driven photocatalytic hydrogen production has been considered as a promising candidate technology for supplying green and sustainable energy source alternative to fossils. But its low solar-to-hydrogen conversion efficiency level hampers its practical application, and lack of effective structure for promoting charge separation is one of the accounts. Herein, intrachain heterojunction structure comprised of donor-acceptor (D-A) blocks has been proved to be one of effective structures for addressing such an issue. Utilizing the facile oxidative coupling polymerization reactions of diacetylene monomers and oligomers, a block heterojunction polymeric photocatalyst named PDTPDPA-BP bearing D-A blocked heterostructure was synthesized by first separative oligomerizations of diacetylene-functionalized dibenzothiophene sulfone (DTP) and triphenylamine (TPA) monomers and then mixed together and undergoing further polymerization. In photocatalytic hydrogen production, PDTPDPA-BP displayed a hydrogen evolution rate of 2164 mu mol g- 1 h-1 , which is much larger than those of PDTP (1270 mu mol g-1 h-1 ) and PTPA (57 mu mol g- 1 h-1 ) synthesized by homopolymerization of DTP and TPA monomers, respectively, and their 1:1 molar ratio physical blend (363 mu mol g- 1 h-1 ). By means of Fluorescence spectroscopy and photo-responsive measurements, it was found PDTPDPA-BP has narrower bandgap and more efficient charge separation than the other polymers. Therefore, the work highlights intrachain heterojunction structure promotes exciton dissociation into free charge carries, and thus deserves the consideration in the design of high performance organic photocatalysts.

As one of the most powerful trifluoromethylation reagents, (trifluoromethyl)trimethylsilane (TMSCF3) has been widely used for the synthesis of fluorine-containing molecules. However, to the best of our knowledge, the simultaneous incorporation of both TMS- and CF3- groups of this reagent onto the same carbon of the products has not been realized. Herein, we report an unprecedented SmI2/Sm promoted deoxygenative difunctionalization of amides with TMSCF3, in which both silyl and trifluoromethyl groups are incorporated into the final product, yielding alpha-silyl-alpha-trifluoromethyl amines with high efficiency. Notably, the silyl group could be further transformed into other functional groups, providing a new method for the synthesis of alpha-quaternary alpha-CF3-amines.