Journals
2025 EN
Achouba Yanis · Peres Basile · Ascoët Steven
+16 more
Abstract Natural peptides from animal venoms effectively modulate ion channel activity. While photoswitches regulate small compound pharmacology, their application to natural peptides rich in disulfide bridges and active on ion channels is novel due to larger pharmacophores. A pilot study integrating azobenzene photoswitches into charybdotoxin (ChTx), known for blocking potassium channels is initiated. Two click‐chemistry‐compatible azobenzene are synthesized differing in length and amide orientation (Az 1 & Az 2 ). Az 1 is grafted onto ChTx at various amino acid positions using L‐azidohomoalanine mutation. ChTx monomers outperformed dimers, particularly with azobenzene at position 14, by exhibiting optimal photoswitching activity. In the cis configuration, Az 1 altered ChTx's pharmacophore, reducing potassium channel blockage, while conversely, Az 2 increased ChTx potency. This study pioneers photoswitch application to complex peptides, leveraging structure‐activity relationships. Successful integration depends on precise azobenzene positioning and chemical grafting guided by SAR insights. This advancement underscores the adaptability of photoswitch technology to intricate peptide structures, offering new avenues for pharmacological modulation.
Journals
2025 EN
Guan Xiushuai · Wang Xiaokun · Zhang Xiaochao
+3 more
Abstract The thermodynamic stability and intrinsic kinetic inertia of CO 2 present a critical challenge for its effective activation in the synthesis of high‐value dimethyl carbonate (DMC). In this work, we report the fabrication of novel O‐Ce‐O vacancy clusters (V O‐Ce‐O ) incorporated into CeO 2 nano‐sheets with a near single‐unit‐cell thickness to construct atomically adjacent multiple active sites on their surfaces. These active sites significantly enhance the activation of both CO 2 and CH 3 OH. Impressively, the as‐prepared CeO 2 with V O‐Ce‐O catalyst exhibits an excellent DMC yield of 31.2 mmol g −1 , surpassing previously reported Ce‐based catalysts under equivalent reaction conditions. Experimental results and theoretical calculations reveal that oxygen vacancy increases the reducibility of lattice oxygen, facilitating CO 2 activation, while cerium vacancies weaken the *CH 3 O adsorption, promoting the coupling reaction between *CH 3 O and *CO 2 to form the intermediate (*CH 3 OC(O) 2 ). Notably, the formation of vacancy clusters reduces the energy barrier for the rate‐controlled step (*CH 3 OC(O) 2 dissociation to *CH 3 OCO), thereby boosting the DMC yield. Our new findings provide valuable insights into surface engineering and active site modulation of cerium‐based catalysts, offering a viable pathway for green resource utilization of CO 2 .
Journals
2025 EN
Sun Yue · Abella Laura · Emge Thomas J.
+8 more
Abstract Endohedral metallofullerenes are chemically more inert compared to empty fullerenes, primarily due to their intramolecular electron transfer. In this work, we report an inverse electron demand Diels–Alder (IEDDA) reaction on M 3 N@C 80 (M=Lu, Sc), where they show significantly higher reactivity than empty fullerenes. The molecular structures of the [4+2] cycloadducts were unambiguously characterized. Moreover, the cycloadducts can fully revert to pristine M 3 N@C 80 via retro‐cycloaddition upon thermal treatment. With the unusual reactivity and reversibility, the IEDDA reaction enables an effective separation approach for metallofullerenes from their soot extracts, opening path to efficient and economical scale‐up synthesis of metallofullerenes in laboratory and industrial settings.
Journals
2025 EN
Chen Zixuan · Ming Hongwei · Li Zhi
+9 more
Abstract Here, we investigate PbSnS 2 , a wide band gap (1.13 eV) compound, as a promising thermoelectric material for power generation. Single crystal X‐ray diffraction analysis reveals its 2D‐layered structure, akin to the GeSe structure type, with Pb and Sn atoms sharing the same crystallographic site. The polycrystalline PbSnS 2 exhibits an intrinsically ultralow lattice thermal conductivity ( κ lat ) of 0.37 W m −1 K −1 at 573 K. However, the low carrier concentration ( n ) leads to suboptimal electrical conductivity ( σ ), capping the ZT value at 0.1. Accordingly, the halogen elements (Cl, Br, and I) are employed as the n‐type dopants to improve the n . The DFT results indicate a significant weakening of Pb/Sn─S bonds upon halogen‐doping, contributing to the observed reduction in κ lat . Our analysis indicates the activation of multiconduction band transport driven by halogen substitution. The PbSnS 1.96 Br 0.04 has a high power factor of five times that of intrinsic PbSnS 2 . Halogen‐doping weakens the Pb/Sn─S bonds and enhances the phonon scattering, leading to an ultralow κ lat of 0.29 W m −1 K −1 at 873 K for PbSnS 1.96 Br 0.04 . Consequently, PbSnS 1.96 Br 0.04 achieved a maximum ZT value of 0.82 at 873 K.
Journals
2025 EN
Yang Jun · Yang Yusheng · Wang Huizhe
+2 more
Abstract Lophine, the first chemiluminescent compound discovered in history, has rarely been applied for in vivo imaging since its discovery in 1877. In this report, we demonstrate that lophine's chemiluminescence emission could be significantly enhanced by caging the imidazole moiety via molecular afterglow mechanism. Notably, our study revealed a rare superoxide anion‐mediated luminescence. Our novel probes JIMI‐11 and JIMI‐12 could be used for in vivo mouse imaging. Compared to its uncaged form JIMI‐6, JIMI‐11 exhibited a significant enhancement (126‐fold) in vitro and a 190‐fold higher emission signal in vivo. JIMI‐11 selectively accumulates in white adipose tissues (WAT) and can be used to monitor changes in WAT mass in a mouse model of type‐1 diabetes. Additionally, it can assess the therapeutic effects of Semaglutide in a mouse model of diet‐induced obesity. Lastly, we designed JIMI‐12 with a reactive oxygen/nitrogen species (ROS/RNS) responsive moiety as the caging group and demonstrated its utility for in vivo imaging of ROS in a lipopolysaccharide (LPS)‐induced inflammatory mouse model. Our studies suggest that re‐designing lophine‐based probes could unlock their potential for both in vitro and in vivo applications. The ability to switch from chemiluminescence to molecular afterglow introduces a novel approach to designing imaging probes.
Journals
2025 EN
Velpula Gangamallaiah · Tomm Emilia · Shen Boxuan
+3 more
Abstract Controlling the surface orientation of DNA origami nanostructures (DON) is crucial for applications in nanotechnology and materials science. While previous work utilized various DON modifications, simple methods for controlling their landing orientation remain scarce. Here, we demonstrate a straightforward approach to control the adsorption orientation of chiral double‐L (CDL) DON on mica by tuning magnesium ion (Mg 2 ⁺) concentration and exploiting global shape distortions. Using atomic force microscopy (AFM), we analyzed the resulting distribution of the mirror‐image orientations, referred to as S and Z orientations, at both buffer/mica and air/mica interfaces and identified conditions resulting in homogenous CDL orientation of 100% S. These results demonstrate how DON conformation and ionic environments influence DON orientation, offering insights for precise nanostructure deposition.
Journals
2025 EN
Huxley Cohan · Fung Ethan · Singh Bara
+5 more
Abstract Bridged nucleic acids (BNAs) are nucleoside analogues (NAs) in which the 2′‐alcohol is linked to the C4′‐position on ribose. In oligonucleotide therapeutics (ONTs), BNAs can impart beneficial properties, including enhanced stability, duplex melting temperatures, and tissue half‐lives. However, their lengthy syntheses challenge medicinal chemistry efforts and larger‐scale production. Here we demonstrate that a wide range of BNAs can be produced with various locking ring sizes and substitution patterns from a common thymine‐containing aldol product through cascade cyclization processes. Critically, several clinically relevant BNAs are now made available in as little as 3–5 steps. We expect these strategies will inspire and support medicinal and process chemistry efforts in this critical area for ONTs.
Journals
2025 EN
Schlichter Antoine · Wolf Alexander · Ferrand Thomas
+27 more
Abstract Glycerophospholipids (GPLs) play important roles in cellular compartmentalization and signaling. Among them, phosphatidic acids (PA) exist as many distinct species depending on acyl chain composition, each one potentially displaying unique signaling function. Although the signaling functions of PA have already been demonstrated in multiple cellular processes, the specific roles of individual PA species remain obscure due to a lack of appropriate tools. Indeed, current synthetic PA analogues fail to preserve all the functions of natural PA. To circumvent these limitations, we developed a novel synthetic approach to produce PA analogues without compromising structural integrity of acyl chains. Moreover, addition of a clickable moiety allowed flexible grafting of different molecules to PA analogues for various biological applications. Hence, this innovation also provides powerful tools to investigate specific biological activities of individual PA species, with potential applications in unraveling complex GPL‐mediated signaling pathways.
Journals
2025 EN
Havens Steven M. · Georgis Brian · Weng Jian
+5 more
Abstract Dopamine is a neurotransmitter essential for motor control, reward processing, and motivation through G‐protein coupled receptor (GPCR) signaling. Recent GPCR‐based real‐time sensors allow for optical monitoring of dopamine release in behaving animals. However, there is still a need for high resolution mapping of dopamine release across large mouse brain volume for systemic studies. To fill this need, we have developed a new chimeric GPCR‐based sensor to detect dopamine with a permanent green fluorescent mark through a combination of computational modeling and rational design. This new sensor, named “Single‐chain Protein‐based Ligand Indication through a Chimerically‐Engineered Integrator Tool” (SPLICEIT), detects dopamine at cellular‐resolution with high specificity and a fourfold signal‐to‐background ratio. We also developed a version of SPLICEIT whose signal can be normalized for varying sensor expression in cell culture and in vivo. This paves the way for further studies into dopamine release across the brain and enables the possibility of whole‐brain dopamine mapping.
Journals
2025 EN
Chen PeiHsuan · Bloom Steven
Abstract Dehydroamino acids (ΔAAs) are vital building blocks in the design and optimization of peptide drugs. The exact olefin geometry, side chain chemotype, and ancillary β‐carbon substituents play a significant role. Unfortunately, general approaches to install these motifs into peptides are lacking, complicated by the instability of unsaturated residues during traditional amide‐bond coupling and failure of divergent protocols, such as oxidative Heck and Horner–Wadsworth–Emmons, to accommodate a complete range of substrate classes. Herein, we conceive and interrogate an original bioorthogonal reagent, β‐sulfonyldehydroamino acid (ΔSulf), that can be site‐specifically encoded into standard peptides through solid‐ or liquid‐phase synthesis. When combined with an aqueous flavin photocatalyst, myriad boronic acids and 525 nm light—a more biologically benign portion of the flavin visible absorption spectra that has not previously been exploited for flavin photoredox catalysis,—this latent residue becomes one of several ( Z )‐ΔAA variants (aromatic, heteroaromatic, aliphatic) via stereoretentive radical conjugate addition and β‐scission. The importance of green light is established through mechanistic studies showing that it tempers radical formation and discourages flavin‐catalyzed isomerization, controlling product selectivity. We apply our original reagent and catalytic platform in a brief medicinal chemistry campaign to discover tetrapeptides that modulate Aβ42 aggregation for the treatment of Alzheimer's disease.