JACS Au最新文献

Electrochemical interfaces are of fundamental importance in electrocatalysis, batteries, and metal corrosion. Finite-field methods are one of the most reliable approaches for modeling electrochemical interfaces in complete cells under realistic constant-potential conditions. However, previous finite-field studies have been limited to either expensive ab initio molecular dynamics or less accurate classical descriptions of electrodes and electrolytes. To overcome these limitations, we present a machine learning-based finite-field approach that combines two neural network models: one predicts atomic forces under applied electric fields, while the other describes the corresponding charge response. Both models are trained entirely on first-principles data without employing any classical approximations. As a proof-of-concept demonstration in a prototypical Au(100)/NaCl-(aq) system, this approach accelerates fully first-principles finite-field simulations by roughly 4 orders of magnitude compared to ab initio molecular dynamics, allowing the extrapolation to cell potentials beyond the training range and accurate prediction of Helmholtz capacitance. Interestingly, we reveal a turnover of both density and orientation distributions of interfacial water molecules at the anode, arising from competing interactions between the positively charged anode and adsorbed Cl^- ions with water molecules as the applied potential increases. This novel computational scheme shows great promise in efficient first-principles modeling of large-scale electrochemical interfaces under potential control.

The rise of multidrug-resistant pathogens, such as Staphylococcus aureus and Mycobacterium tuberculosis, underscores an urgent need for therapeutic innovation. The antibiotic development pipeline targeting these bacteria is critically limited, with most discovered candidates exhibiting structurally similar features of prominent chemical entities and with well-established molecular targets or binding modes. The myxobacterial α-pyrone antibiotics, myxopyronins, represent a highly promising compound class due to their ability to inhibit RNA polymerase by binding to the "switch region", a distinct binding site to that of standard-of-care antibiotics. Mutasynthesis, leveraging engineered microorganisms and tailored precursors, provides a viable alternative to total synthesis for generating novel derivatives. This study utilized a heterologous expression system in Myxococcus xanthus DK1622 to generate analogs. Two carrier protein domain mutants were engineered to facilitate mutasynthesis-based production of structurally diverse derivatives. A trifluoromethyl-modified analog, once accessible only through total synthesis but now obtained via mutasynthesis, exhibits potent antimicrobial activity against Gram-positive pathogens including Mycobacterium tuberculosis and favorable in vitro absorption, distribution, metabolism, excretion and toxicity properties. These findings highlight a promising pathway for developing optimized α-pyrone antibiotics to address the global antimicrobial-resistance crisis.

Monolayer-confined supercooled water exhibits unique dynamic behavior with broad implications in science and engineering, from biomolecular interactions and energy storage to cryopreservation. However, under such extreme confinement, its dynamical heterogeneity, which links closely to early ice formation, remains poorly understood. We used isoconfigurational analysis and van Hoff correlation functions to study dynamical heterogeneity in protein-confined water monolayers at 240 K. Protein confinement was found to markedly attenuate the local-environment dependence of water dynamical heterogeneity. As a result, the usual coupling between slow dynamics and incipient ice-like order seen in bulk water is greatly diminished under confinement, especially in the ice-nucleation protein PsINP. Consistently, no precrystallization slowdown occurs for water at protein interfaces, whereas bulk water shows a pronounced slowdown long before ice nucleation, indicating a distinct freezing mechanism under confinement. These findings provide new insights into how protein environments modulate deeply supercooled water's behavior, with implications for controlling ice formation at the nanoscale.

Gene transfection visualization provides intuitive and direct evidence of gene function and cellular signaling pathways through dynamic, real-time tracking of gene delivery and expression. In this work, we synthesized two tetraphenylethylene-backboned AIE (aggregation-induced emission) fluorophores with acidic tetrazole moieties, which were subsequently integrated with branched polyethylenimine (BPEI) gene carriers via electrostatic interactions to construct a fluorescent gene delivery complex system. This self-reporting gene delivery platform combines responsive AIE fluorescence properties with good biocompatibility while maintaining the vector's binding competence to the host cell in living systems. By employing GFP (green fluorescence protein)-tagged plasmid DNA in a proof-of-concept study, the system enables real-time spatiotemporal tracking and precise localization of gene transporting processes into HeLa cells. Quantitative flow cytometric analysis revealed enhanced transfection efficiency for the TPE-4TA/BPEI/DNA complexes (52.7%) compared to conventional BPEI vectors (47.9%). This study not only contributes to a better understanding of the gene transfection process but also provides valuable concepts and methods for the design and development of gene transfection systems.

1,2-cis-2-Amino glycosidic linkages are prevalent in biologically important molecules; however, they are difficult to form reliably in high stereoselectivity. Herein, we disclose a catalyst-free, α-stereospecific oxime O-glycosylation in hexafluoroisopropanol (HFIP) that assembles diverse N-O-linked 2-nitro-α-glycosides (60 examples), enabling facile access to 1,2-cis-2-amino glycoside mimetics. The synthetic utility of this approach is highlighted by the late-stage functionalization of complex molecules and various synthetic transformations. Nuclear magnetic resonance (NMR) studies reveal strong hydrogen-bonding (HB) interactions between HFIP and 2-nitroglycals/oximes. Computational studies reveal a novel glycosylation mechanism in which aggregated HFIP trimers play a critical role in facilitating HB activation of substrates and then enable the α-stereospecific, concerted 1,4-addition of oxime to 2-nitroglycal and protonation through a proton shuttle-mediated macrocyclic transition state. Overall, this work uncovers the HFIP trimer as an efficient hydrogen-bond catalyst for stereoselective glycosylation, providing a powerful tool for α-stereospecific synthesis of N-O-linked 1,2-cis-2-amino glycosides.

[This corrects the article DOI: 10.1021/jacsau.4c00177.].

Evaluating the long-term stability of electrocatalysts under operational conditions is critical for understanding performance degradation in fuel cells, electrolyzers, and metal-air batteries. Conventional electrochemical techniques, such as chronoamperometry and chronopotentiometry, often rely on simple current or overpotential versus time correlations, offering limited insight into the evolving structure-performance relationships. In this study, we introduce a time-resolved electrochemical impedance analysis (tr-EIA) protocol that enables the real-time tracking of key electrochemical parameters, including current/overpotential, electrochemical double-layer capacitance, charge transfer resistance, electrolyte resistance, and process relaxation times, all in a single experiment. By applying tr-EIA to commercial RuO₂ and Pt/C catalysts across representative electrochemical reactions, we reveal time-resolved structural dynamics and uncover distinct degradation pathways at different stages of operation. Notably, structural degradation tied to changes in the electrochemically active surface area is distinguished from kinetic factors, such as increased resistance, with quantitative insights provided by the proposed surface area contribution factor. This single-run tr-EIA approach delivers a comprehensive understanding of electrochemical and structural evolution, offering a powerful tool to decode the mechanisms governing electrocatalyst stability under realistic operating conditions.

The development of modular difunctionalization strategies for unsaturated hydrocarbons is of particular interest, as it enables access to complex building blocks in a single step. Although great progress has been recently achieved in this field, difunctionalization of simple, nonconjugated alkenes represents a substantial challenge. Inspired by the radical rebound paradigm found in metalloenzymes, radical ligand transfer (RLT) catalysis has recently emerged as a powerful and broadly applicable strategy for the selective functionalization of alkyl radicals. Here, we present our advancements on the metallaphotoredox platform, which leverages the efficient cooperation between photoredox and cobalt RLT catalysis. A variety of electrophilic, functionalized carbon-centered radicals can be generated and efficiently incorporated into alkene derivatives, while the resulting nucleophilic radicals are further harnessed through homolytic substitution at a cobalt-bound ligand, enabling controlled transfer of a halogen nucleophile. The method accommodates a wide variety of radical precursors and exhibits excellent functional group tolerance, enabling efficient access to chloroalkyl derivatives. An integrated approach combining experimental and density functional theory studies revealed fundamental aspects of cobalt-mediated RLT and provided a plausible explanation for the key roles of the silver carbonate additive.

We report an unprecedented transformation between phenanthrene-9,10-diones and phosphorus ylide, where methylenetriphenylphosphane exhibits dual reactivity patterns, enabling both olefination and ring expansion to construct seven-membered carbocycles in moderate to good yields. This process proceeds through initial Wittig olefination followed by an unusual alkenyl group 1,2-migration pathway from either an oxaphosphetane or betaine intermediate. Mechanistic studies, including deuterium-labeling experiments and isolation of key intermediates, support a pathway involving conformationally controlled ring expansion.

Vaccine adjuvants are substances that are coadministered with antigens to enhance the immune response. Lablaboside F, a triterpene oleanolic acid β-linked to two trisaccharide chains on its eastern and western sides, emerged as a promising adjuvant candidate due to exhibiting robust adjuvanticity and low toxicity . We developed a β-stereoselective glycosylation method using a [PhenH]⁺[BF₄]^- catalyst to glycosylate oleanolic acid with C2-branched oligosaccharides, synthesizing lablaboside F and structural derivatives (S1-S8) as a result of constructing the target oligosaccharide. This approach simplifies the synthetic process when varying sugars are used and provides a platform for structure-activity relationship studies. Lablaboside F and S1-S8 were tested in vivo and in vitro for adjuvant activity, toxicity, and cytokine production. The entire branched trisaccharide on the western side of lablaboside F is not essential for adjuvant activity. Six derivatives showed low toxicity, while four increased pro-inflammatory cytokine levels. Notably, compound S5, composed of oleanolic acid and the eastern trisaccharide, demonstrated a favorable safety profile in vitro and higher antigen-specific total IgG levels than lablaboside F in vivo, without eliciting IgE production that can lead to allergic reactions. These findings advance our understanding of saponin structure-function relationships and provide a pathway for developing nontoxic adjuvants.