Journal of the American Chemical Society最新文献

We report how gases impact the hydrogen concentration in the palladium metal lattice during electrochemical hydrogen loading. We built a unique in situ X-ray diffraction cell, where one surface of a palladium membrane is electrochemically loaded with hydrogen and the other surface faces a gas flow. Under N₂ and CO₂ gas, rapid phase transformation from α-Pd to β-PdH occurred with moderate H/Pd ratios of 0.63 ± 0.02 and 0.64 ± 0.01, respectively. Under CO gas, the α → β phase transformation was also fast, but the H/Pd ratio increased to 0.752 ± 0.001. In contrast, the O₂ gas induced a more gradual α → β phase transformation, achieving the maximum H/Pd ratio of 0.66 ± 0.03, followed by the reverse β → α phase transformation. Gas chromatography confirmed that the increased H/Pd ratio under CO originates from the suppressed recombination of hydrogen atoms into H₂ gas. Additionally, we found that O₂ reacts with hydrogen on the Pd surface to form water and hydrogen peroxide, which together promote hydrogen removal. These findings demonstrate that electrochemical hydrogen loading of Pd is governed not only by the applied electrochemical potential but also by gas-surface interactions.

Four-electron reduction of aromatic compounds to produce four-electron reduced compounds has been extremely difficult because of the highly negative reduction potentials. Herein, we report for the first time formation of stable four-electron reduced aromatic molecules using nitrogen-doping at the peripheral positions of a Zn^II complex of a quadruply fused porphyrin (1), containing four imino-nitrogens in the "formal" 30π aromatic circuit. Peripheral nitrogen atoms have been demonstrated to form hydrogen bonds, as indicated by X-ray diffraction analysis. Addition of a strong acid such as triflic acid (TfOH) enables diprotonation of 1 and the diprotonated form (H₂1²⁺) of 1 shows a large positive shift of the first reduction potential. Furthermore, in the presence of an excess amount of TfOH, chemical or electrochemical reduction causes further protonation of the imino-nitrogen atoms of 1, allowing further reduction of 1 through a proton-coupled electron transfer (PCET) mechanism. The multielectron PCET processes are supported by DFT calculations to clarify a large change in the pK_a of the outer imine nitrogens before and after the 1e^--reduction. Consequently, 1 undergoes its tetraprotonation and four-electron-reduction at a relatively positive potential to form H₄1⁰, which bears the 34π aromaticity despite the fact that it is unable to draw an aromatic circuit with alternating single and double bonds. It should be noted that this is the first time to demonstrate multistep PCET of a π-expanded aromatic system and to achieve the emergence of unique aromatic conjugation with 34π electrons.

The emergence of multidrug-resistant (MDR) pathogens has urged us to find new antimicrobial strategies. Phosphatidylglycerol (PG) is an attractive bacterial-specific lipid target but is targeted by only one clinical agent, daptomycin. Yet daptomycin, like most reported PG binders, binds PG through an imprecise hydrophobic-electrostatic mode, necessitating a relatively large molecular size. This requirement, together with its strict Ca²⁺ dependence, significantly limits its efficacy. Here, we report bis-pyridinium amides (BisPAs), a rationally designed class of small molecules capable of precisely recognizing PG through amide-diol hydrogen bonding coupled with pyridinium-phosphate anionic-π interaction, independent of environmental conditions such as Ca²⁺. The lead compound, BisPA14, with ∼one-third the molecular weight of daptomycin, exhibits comparable PG-binding affinity, with K_d(BisPA14) = 1.4 × 10^-6 M versus K_d(daptomycin-Ca²⁺) = 0.9 × 10^-6 M. BisPA14 disrupts PG self-assembly and membrane integrity and simultaneously engages bacterial DNA as a secondary intracellular target. This dual-targeting mechanism enables BisPA14 to eradicate proliferating, tolerant, and persister bacterial populations while suppressing resistance evolution. It remains active in serum-containing environments, protects host cells from bacterial damage, and demonstrates excellent biocompatibility and strong therapeutic efficacy in intraperitoneal, pulmonary, and bloodstream methicillin-resistant Staphylococcus aureus infection models. As a synthetically accessible small molecule that functionally mimics and improves upon daptomycin's lipid-targeting mechanism, this work establishes a secondary-bonding-driven PG-recognition paradigm for combating MDR bacterial infections.

Circulating tumor DNA (ctDNA) offers a promising avenue for noninvasive cancer diagnosis and prognosis, yet its effective utilization is fundamentally limited by rapid in vivo clearance and nuclease-mediated degradation, resulting in extremely low bioavailability. In addition, conventional in vitro recognition-based ctDNA detection means may potentially compromise the diagnostic accuracy. Here, we report an in vivo spatiotemporal protection and recognition strategy that actively enhances ctDNA bioavailability, enabling accurate early cancer diagnosis and quantitative monitoring of disease progression and therapeutic response. This strategy integrates immunoglobulin G-modified liposomes to transiently saturate the mononuclear phagocyte system, thereby suppressing ctDNA clearance, together with systemically administered anti-dsDNA monoclonal antibodies that protect ctDNA from nuclease degradation. The synergistic in vivo intervention enhances recoverable ctDNA levels by up to 56.2-fold relative to unprotected controls. The protected ctDNA subsequently undergoes sequence-specific hybridization with an in vivo recognition nanoprobe, triggering the release and renal excretion of locked nucleic acid (LNA) reporter strands. These urinary LNAs further induce the dissolution of a horseradish peroxidase (HRP)-encapsulated DNA gel to liberate HRP, which generates highly amplified current on a disposable sensor electrode, thereby markedly improving detection sensitivity for noninvasive identification of small tumors down to 30 mm³. This methodology further enables quantitative monitoring of tumor progression and assessment of doxorubicin (DOX)-mediated therapeutic efficacy, underscoring its robust broad potential for convenient and accurate cancer diagnosis and treatment evaluation.