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.
Journals
2025 EN
Weaver Jason F. · Xiang Shuting · Jamir Jovenal
+19 more
Abstract Self‐stabilized, heterometallic pair‐sites can enable fine‐tuning of catalytic functionality while also mitigating dynamic structural changes that degrade catalytic performance. This study demonstrates the development and characterization of trimetallic Pt x Cr x Ag 1‐2x ( x ≤ 0.1) alloys with active Pt–Cr pair‐ensembles for non‐oxidative ethanol dehydrogenation, leveraging predictions that favorable bonding stabilizes Pt–Cr pairs diluted in Ag. Operando X‐ray absorption spectroscopy confirms the preferential formation and stability of Pt–Cr pairings dispersed throughout the Ag matrix, and ambient‐pressure X‐ray photoelectron spectroscopy shows that Pt–Cr sites have significant activity for ethanol dehydrogenation, while suppressing reaction processes that deactivate binary Pt–Ag and Cr–Ag alloys. This work demonstrates that stabilizing heterometallic pair sites within trimetallic alloys provides a new avenue for designing catalysts with discrete active sites that are durable and highly selective.
Journals
2025 EN
Guo Chaofei · Liu Tiancun · Wang Zhenzhen
+5 more
Abstract Although the catalytic activity is heavily reliant on the electronic structure of the catalyst, understanding the impact of electron spin regulation on electrocatalytic performance is still rarely investigated. This work presents a novel approach involving the single‐atom coordination of cobalt (Co) within metalloporphyrin‐based three‐dimensional covalent organic frameworks (3D‐COFs) to facilitate the catalytic conversion for sodium‐iodine batteries. The spin state of Co is modulated by altering the oxidation state of the porphyrin‐centered Co, achieving optimal catalysis for iodine reduction. Experimental results demonstrate that Co II and Co III are incorporated into the 3D‐COFs, exhibiting spin ground states of S=1/2 and S=0, respectively. The low spin state of Co III is favorable to hybridize with the sp 3d orbitals of I 3 − , thus facilitating the conversion of I 3 − to I − . Density‐functional theory (DFT) calculations further reveal that the presence of Co III enhances iodide adsorption and accelerates the formation of NaI in 3D‐COFs‐Co III , thereby promoting its rapid kinetic behaviors. Notably, the I 2 @3D‐COFs‐Co III cathode achieves a high reversible capacity of 227.7 mAh g −1 after 200 cycles at 0.5 C and demonstrates exceptional cyclic stability, exceeding 2000 cycles at 10 C with a minor capacity fading rate of less than one 0.01 % per cycle.
Journals
2025 EN
Kmiec Steven · Ruoff Erick · Manthiram Arumugam
Abstract Sodium‐based batteries are gaining momentum due to the abundance and lower cost of sodium compared to lithium. Solid‐state sodium batteries can also provide further safety advantages. However, sodium‐based solid‐state electrolytes (SSEs) that meet all the rigorous requirements, such as high ionic conductivity, oxidative stability with the cathode, and ease of processability, are lacking. We present here a new class of sodium‐based oxyhalide electrolytes NaNbCl 6‐2x O x with a facile mechanochemical synthesis. The oxyhalide NaNbCl 4 O exhibits close to two orders of magnitude higher ambient‐temperature sodium‐ion conductivity (1.03×10 −4 S cm −1 ) compared to the halide counterpart NaNbCl 6 (3×10 −6 S cm −1 ). Structural motifs unique to the oxygen content in NaNbCl 6‐2x O x are identified with 23 Na and 93 Nb magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy and x‐ray diffraction (XRD). Solid‐state sodium batteries assembled with NaNbCl 4 O electrolyte and the cobalt‐ and nickel‐free layered Na 0.70 Fe 0.3 Mn 0.65 Al 0.05 O 2 cathode exhibit a maximum discharge capacity of 155 mAh g −1 with good cycle life at ambient temperature.
Journals
2025 EN
Roshanzadeh Amir · Medeiros Hyllana C. D. · Herrera Christopher K.
+8 more
Abstract Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Here, we report the discovery of cyanine‐carborane salts as potent photosensitizers (PSs) that harness the near‐infrared (NIR) absorbing [cyanine + ] with the inertness of [carborane − ]. The implementation of [cyanine + ] [carborane − ] salts dramatically enhance cancer targeting of the PSs and decrease cytotoxicity. We characterize the cellular uptake of the cyanine‐carborane PSs, organelle localization, generation of reactive oxygen species (ROS) with the ability to cogenerate multiple ROS species, suppression of pro‐metastatic pathways, and activation of apoptotic pathways. We further demonstrate the ability of optimized PSs to eliminate tumors in vivo using an orthotopic mouse model of breast cancer. These newly developed [cyanine + ] [carborane − ] salt PSs introduce a potent therapeutic approach against aggressive breast cancer while decreasing side effects.