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The features of well-conjugated and planar aromatic structures make π-conjugated luminescent materials suffer from aggregation caused quenching (ACQ) effect when used in solid or aggregated states, which greatly impedes their applications in optoelectronic devices and biological applications. Herein, we reduce the ACQ effect by demonstrating a facile and low cost method to co-assemble polycyclic aromatic hydrocarbon (PAH) chromophores and octafluoronaphthalene together. Significantly, the solid photoluminescence quantum yield (PLQYs) for the as-resulted four micro/nanococrystals are enhanced by 254%, 235%, 474 and 582%, respectively. Protection from hydrophilic polymer chains (P123 (PEO 20 -PPO 70 -PEO 20 )) endows the cocrystals with superb dispersibility in water. More importantly, profiting from the above-mentioned highly improved properties, nano-cocrystals present good biocompatibility and considerable cell imaging performance. This research provides a simple method to enhance the emission, biocompatibility and cellular permeability of common chromophores, which may open more avenues for the applications of originally non- or poor fluorescent PAHs. Organic luminescent materials are often used in modern technologies, but aggregation induced quenching caused by planar aromatic structures hampers their applicability. Here, the authors demonstrate a facile co-assembly method for luminescent cocrystals and protection with hydrophilic PEO chains which allow good dispersibility in water.

We show that the different bond orders of individual carbon-carbon bonds in polycyclic aromatic hydrocarbons and fullerenes can be distinguished by noncontact atomic force microscopy (AFM) with a carbon monoxide (CO)—functionalized tip. We found two different contrast mechanisms, which were corroborated by density functional theory calculations: The greater electron density in bonds of higher bond order led to a stronger Pauli repulsion, which enhanced the brightness of these bonds in high-resolution AFM images. The apparent bond length in the AFM images decreased with increasing bond order because of tilting of the CO molecule at the tip apex.

This protocol is intended to provide chemists who discover or make new organic compounds with a valuable tool for validating the structural assignments of those new chemical entities. Experimental 1 H and/or 13 C NMR spectral data and its proper interpretation for the compound of interest is required as a starting point. The approach involves the following steps: (i) using molecular mechanics calculations (with, e.g., MacroModel) to generate a library of conformers; (ii) using density functional theory (DFT) calculations (with, e.g., Gaussian 09) to determine optimal geometry, free energies and chemical shifts for each conformer; (iii) determining Boltzmann-weighted proton and carbon chemical shifts; and (iv) comparing the computed chemical shifts for two or more candidate structures with experimental data to determine the best fit. For a typical structure assignment of a small organic molecule (e.g., fewer than ∼10 non-H atoms or up to ∼180 a.m.u. and ∼20 conformers), this protocol can be completed in ∼2 h of active effort over a 2-d period; for more complex molecules (e.g., fewer than ∼30 non-H atoms or up to ∼500 a.m.u. and ∼50 conformers), the protocol requires ∼3–6 h of active effort over a 2-week period. To demonstrate the method, we have chosen the analysis of the cis - versus the trans -diastereoisomers of 3-methylcyclohexanol ( 1- cis versus 1- trans ). The protocol is written in a manner that makes the computation of chemical shifts tractable for chemists who may otherwise have only rudimentary computational experience.

The neuroprotective role of schizandrin (SA) in cerebral ischemia-reperfusion (I/R) was recently highlighted. However, whether SA plays a regulatory role on autophagy in cerebral I/R injury is still unclear. This study aimed to explore whether the neuroprotective mechanisms of SA were linked to its regulation of AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/autophagy pathway in vivo and in vitro. The present study confirmed that SA significantly improved oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced PC12 cells injury. The results of immunoblotting and confocal microscope showed that SA decreased autophagy in OGD/R-injured PC12 cells, which was reflected by the decreased Beclin-1 and LC3-II expression, autophagy flux level, and LC3 puncta formation. In addition, the autophagy inducer rapamycin partially prevented the effects of SA on cell viability and autophagy after OGD/R, whereas the autophagy inhibitor 3-methyladenine (3-MA) exerted the opposite effect. The results of Western blotting showed that SA markedly decreased the phosphorylation of AMPK (p-AMPK), whereas the phosphor-mTOR (p-mTOR) levels increased in the presence of OGD/R insult. Furthermore, pretreatment with the AMPK inducer AICAR partially reversed the protective effects and autophagy inhibition of SA. However, AMPK inhibitor Compound C pretreatment further promoted the inhibition of SA on autophagy induction and cell damage induced by OGD/R. Taken together, these findings demonstrate that SA protects against OGD/R insult by inhibiting autophagy through the regulation of the AMPK-mTOR pathway and that SA may have therapeutic value for protecting neurons from cerebral ischemia.

A novel double aza-oxa[7]helicene was synthesized from the commercially available N1,N4-di(naphthalen-2-yl)benzene-1,4-diamine and p-benzoquinone in two steps. Combining the acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero[7]helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.

Schisandra chinensis (Turcz.) Baill. (S. chinensis) and Schisandra sphenanthera Rehd. et Wils (S. sphenanthera) are called “Wuweizi” in traditional Chinese medicine, and they have distinct clinical applications. To systematically compare the differential characteristics of S. chinensis and S. sphenanthera, this study employed ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatography–mass spectrometry (GC-MS) to construct chemical profiles of these two species from different regions. In total, 31 non-volatiles and 37 volatiles were identified in S. chinensis, whereas 40 non-volatiles and 34 volatiles were detected in S. sphenanthera. A multivariate statistical analysis showed that the non-volatiles tigloygomisin P, schisandrol A, schisantherin C, and 6-O-benzoylgomisin O and the volatiles ylangene, γ-muurolene, and β-pinene distinguish these species. Additionally, the metabolism of oxygen free radicals can contribute to the development of various diseases, including cardiovascular and neurodegenerative diseases. Therefore, antioxidant activities were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) scavenging assays. The results showed that S. sphenanthera exhibited significantly higher antioxidant potential. A gray relational analysis indicated that the key contributors to the antioxidant activity of S. chinensis were schisandrol A, gomisin G, schisantherin C, pregomisin, gomisin J, and schisantherin B. For S. sphenanthera, the key contributors included gomisin K2, schisantherin B, gomisin J, pregomisin, schisantherin C, schisandrin, gomisin G, schisantherin A, schisanhenol, and α-pinene. The identification of the differential chemical markers and the evaluation of the antioxidant activities provide a foundation for further research into the therapeutic applications of these species. This innovative study provides a robust framework for the quality control and therapeutic application of S. chinensis and S. sphenanthera, offering new insights into their medicinal potential.

Homochirality is essential to many biological systems, and plays a pivotal role in various technological applications. The generation of homochirality and an understanding of its mechanism from the single-molecule to supramolecular level have received much attention. Two-dimensional chirality is a subject of intense interest due to the unique possibilities and consequences of confining molecular self-assembly to surfaces or interfaces. Here, we report the perfect generation of two-dimensional homochirality of porous molecular networks at the liquid–solid interface in two different ways: (i) by self-assembly of homochiral building blocks and (ii) by self-assembly of achiral building blocks in the presence of a chiral modifier via a hierarchical structural recognition process, as revealed by scanning tunnelling microscopy. The present results provide important impetus for the development of two-dimensional crystal engineering and may afford opportunities for the utilization of chiral nanowells in chiral recognition processes, as nanoreactors and as data storage systems. The generation of two-dimensional homochiral porous molecular networks at the liquid–solid interface is described. Using scanning tunnelling microscopy, the formation of homochiral porous networks was observed both from solutions of homochiral molecules and from solutions of achiral molecules in the presence of a small amount of a chiral modifier.

Myocardial microvascular injury plays a critical role in myocardial ischemia‑reperfusion injury (MI/RI), and ferroptosis has emerged as an important contributor to cardiac damage. Although Schizandrin A (Sch) possesses cardioprotective effects, its clinical application is limited by poor stability and low bioavailability. This study aimed to develop a CMEC‑targeted delivery system for Sch and evaluate its ability to attenuate ferroptosis in cardiac microvascular endothelial cells (CMECs), thereby alleviating MI/RI. A cardiac endothelium‑targeting peptide CRPPR was conjugated to DSPE‑PEG2000 to prepare a Sch‑loaded nanoparticle (CRPPR@Sch). MI/RI was induced in mice by 45‑minute ischemia followed by 6‑hour reperfusion. CRPPR@Sch, free Sch, or non‑targeted DSP@Sch was administered intravenously for seven consecutive days. Cardiac function, infarct size, microvascular integrity and ferroptosis‑related markers were evaluated in vivo. In vitro, CMECs were exposed to hypoxia/reoxygenation (H/R), and ferroptosis was assessed. CRPPR@Sch efficiently accumulated in cardiac endothelial cells, improved cardiac function, reduced infarct size, restored microvascular perfusion, and alleviated CMEC injury. RNA‑seq indicated that CRPPR@Sch suppressed ferroptosis‑related pathways. In vitro and in vivo experiments demonstrated that CRPPR@Sch significantly up‑regulated GPX4 expression, reduced ROS, lipid peroxidation and ferroptosis markers. Moreover, TRIM25 expression was elevated in MI/RI mice and H/R‑injured CMECs. Co‑immunoprecipitation and molecular dynamics simulations revealed that Sch binds to GPX4 and interferes with TRIM25‑mediated GPX4 ubiquitination and degradation. CRPPR@Sch effectively delivers Sch to cardiac endothelium, stabilizes GPX4 by disrupting the TRIM25‑GPX4 interaction, and thus inhibits ferroptosis in CMECs, ultimately protecting against myocardial microvascular injury in MI/RI.

The P2X7 receptor is an ATP-gated ion channel that activates inflammatory pathways involved in diseases such as cancer, atherosclerosis, and neurodegeneration. However, despite the potential benefits of blocking overactive signaling, no P2X7 receptor antagonists have been approved for clinical use. Understanding species-specific pharmacological effects of existing antagonists has been challenging, in part due to the dearth of molecular information on receptor orthologs. Here, to identify distinct molecular features in the human receptor, we determine high-resolution cryo-EM structures of the full-length wild-type human P2X7 receptor in apo closed and ATP-bound open state conformations and draw comparisons with structures of other orthologs. We also report a cryo-EM structure of the human receptor in complex with an adamantane-based inhibitor, which we leverage, in conjunction with functional data and molecular dynamics simulations, to design a potent and selective antagonist with a unique polycyclic scaffold. Functional and structural analysis reveal how this optimized ligand, termed UB-MBX-46, interacts with the classical allosteric pocket of the human P2X7 receptor with subnanomolar potency and high selectivity, revealing its significant therapeutic potential. Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus . Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro -hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus . This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development. Structurally diverse natural products are a promising source of antibiotics. Here, the authors report the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners and discover a compound active against both drug-sensitive and drug-resistant Staphylococcus aureus .