Journal of the American Chemical Society最新文献

Activity-based ubiquitin probes (Ub-ABPs) have been instrumental in interrogating deubiquitinases (DUBs), yet conventional Ub-ABPs lack the substrate-specific and site-specific contextual cues required to investigate nucleosomal DUBs, whose activity is tightly regulated by the chromatin environments. Here, we developed a substrate-directed nucleosomal DUB activity-based probe (SD-NucDUB-ABP) employing a disulfide-trapping mechanism. This probe features a 2,2'-dithiodipyridine-activated 2-mercaptoethyl modification on ubiquitinated histone isopeptide amide, enabling selective covalent capture of nucleosome-interacting DUBs via their catalytic cysteines while remaining resistant to hydrolysis. Using this strategy, we synthesized the H2AK15Ub^AT nucleosome probe and applied it in the activity-based profiling of DUBs in nuclear lysates of DNA-damaged HeLa cells. Subsequent biochemical analyses confirmed USP3 as a bona fide DUB for H2AK15Ub nucleosomes. Cross-linking mass spectrometry (XL-MS) further delineated the spatial interaction network among USP3, Ub, and the nucleosome, providing mechanistic insights into H2AK15 deubiquitination. Furthermore, we extended this strategy to other nucleosomal ubiquitination sites (H2AK119Ub and H2BK120Ub), capturing their cognate DUBs (USP16 and Ubp10, respectively). The SD-NucDUB-ABP platform thus enables integrated proteomic discovery and mechanistic dissection of nucleosome-specific deubiquitination, providing a versatile chemical tool for epigenetic research at the intersection of chemical biology and chromatin biology.

The electrochemical nitrate reduction to ammonia (NO₃RR) has garnered considerable interest as a highly promising route for value-added nitrate conversion. However, the efficiency of NO₃RR is often limited by the inadequate supply of active hydrogen species (H*) and their preferential consumption via the competing hydrogen evolution reaction (HER), both of which stem from the lack of precise management of H*. Herein, we report a rationally designed ternary catalyst Pt@ZIF@Cu to achieve precise control and targeted utilization of H*. The spatially separated Pt and Cu sites serve as independent centers for H* generation and consumption, respectively. A ZIF layer is introduced as a hydrogen buffer, facilitating the efficient migration of H* from Pt sites to Cu sites with a reduced energy barrier, which ultimately enhances the NO₃RR performance on the Cu surface while simultaneously suppressing HER at the Pt sites. The ternary Pt@ZIF@Cu exhibits superior NO₃RR performance with an ammonia yield rate of up to 4.6 mmol h^-1 mg_cat^-1 at -0.8 V (vs RHE) through meticulous H* management. Furthermore, it demonstrates enhanced performance (8.34 mmol h^-1 mg_cat^-1) in a membrane electrode assembly (MEA) under ampere-level current densities, and enables the convenient preparation of high-purity solid ammonium products via Ar-stripping.

Prodrug strategies traditionally rely on masking polar functional groups of bioactive molecules with protecting units that can be removed by specific stimuli in biological settings. Here, we introduce an alternative uncaging approach that bypasses the need for heteroatom handles, based on reversible masking of aromatic C-H bonds with thianthrenium groups. Unmasking is triggered by low-energy photoredox activation, which generates aryl radicals that are rapidly reduced by endogenous bioreductants to restore the native C-H bond. Beyond establishing the feasibility of photoredox radical chemistry in living cells, we demonstrate a proof-of-concept application of this strategy for the modulation of activity of antifungal agents.

Understanding the spin and charge transfer (CT) process at the 2D semiconductor interface is of both fundamental and practical importance for photocatalysis and optoelectronics. However, experimentally resolving the interfacial CT dynamics with both species, temporal, and energy information remains challenging. Herein, we exploit the spin degree of freedom to directly visualize the formation and cooling of hot interlayer CT excitons at the 2D interface using spin-resolved ultrafast transient absorption (TA) spectroscopy. We reveal a universal two-stage exciton interfacial process: an initial ultrafast (∼0.1 ps) spin-conserved electron injection forming a weakly bound delocalized hot CT exciton with a hot electron in the accepting layer, followed by a slow hot electron intralayer cooling over hundreds of femtoseconds to yield a lowest-energy tightly bound CT exciton with a band-edge electron and hole. The markedly slower cooling relative to the transfer step indicates that the electron and hole at the 2D type II interface can maintain a transient loosely bound and delocalized phase, which can promote the long-range charge separation and light-to-charge conversion. Indeed, spin-resolved TA measurements on ternary heterostructures directly confirm the spin-conserved long-range electron transfer across multiple interfaces. This study establishes a unified picture of spin-dependent interfacial charge transfer and cooling at a 2D semiconductor interface and provides guiding principles in next-generation light-harvesting and photon-to-charge conversion devices.