Journal of the American Chemical Society最新文献

Iridium oxide (IrO₂) is the state-of-the-art electrocatalyst for water oxidation in electrolyzers, yet it suffers from instability under operating conditions. Here, we combine first-principles modeling with in situ liquid-phase transmission electron microscopy and device-scale characterization to resolve the atomic-scale morphology and dissolution dynamics of IrO₂ nanocrystals. Our computational Wulff constructions uniquely incorporate high-index facets, providing new insights into thermodynamic facet-dependent stability under operating conditions. Atomically resolved studies reveal multiple distinct collective dissolution pathways, including high-index facet formation, monolayer reconstruction, step-edge formation, and monolayer delamination on {110} surfaces. Device-scale studies confirm that electrochemical operation results in high-index facet formation. Ab initio molecular dynamics simulations further show that initial dissolution kinetics are facet-dependent. These findings highlight how combining in situ imaging with first-principles modeling reveals atomic-scale dynamics that influence material performance.

Enantioenriched β-allyl carbonyl compounds constitute an important class of versatile chiral building blocks that can be transformed into a variety of intermediates and utilized in the synthesis of numerous biologically active natural products. Catalytic enantioselective conjugate allyl addition to simple α,β-unsaturated esters provides one of the most efficient approaches for access to such moieties. However, this reaction has not been accomplished for a long time in synthetic chemistry. The natural tendency for 1,2-addition or the formation of stable π-allyl complexes and reluctance to 1,1-reductive elimination make such a reaction very challenging. Herein, by means of copper(I)-N-heterocyclic carbene (NHC) catalysis, such a problem is successfully addressed, and a broad range of simple α,β-unsaturated esters undergo conjugate allylation with commercially available allylBpin in moderate to high yields with excellent regioselectivity and high enantioselectivity. The hydroxyl group in the NHCs was found to be indispensable for both a high yield and high enantioselectivity. Based on control experiments and DFT calculations, a redox reaction pathway involving reversible oxidative addition of allyl cuprate to simple α,β-unsaturated esters, isomerization of Cu(III) π-allyl species, and unique 3,3'-allyl-allyl reductive elimination is proposed rationally. Finally, the synthetic utility of the present methodology is showcased by its application in efficient asymmetric formal syntheses of three bioactive natural products and transformations of the allylation product.

Natural products remain a vital source of therapeutic innovation, but their structural complexity often limits the systematic optimization and clinical translation. This challenge is exemplified by the fungal metabolite fumagillin, a covalent inhibitor of methionine aminopeptidase 2 (MetAP2), which advanced toward clinical development but whose semisynthetic derivatives were discontinued in trials for cancer and obesity because of adverse effects. To overcome these barriers, we reengineered the fumagillin biosynthetic pathway in Aspergillus nidulans to expand chemical diversity, uncovering its natural analog ovalicin as a more potent agent active against Entamoeba histolytica. Although ovalicin had never been developed clinically, our analyses revealed that its rapid degradation by hepatic cytochrome P450 enzymes underlies its therapeutic ineffectiveness in preclinical studies. We then established a chem-bio hybrid platform that integrates pathway-engineered biosynthesis with site-selective chemical derivatization to address this metabolic fragility. Introduction of a C6-hydroxyl group as a built-in functional handle enabled preparative-scale diversification and the synthesis of about 30 analogs. Several C6-modified derivatives maintained subnanomolar MetAP2 inhibition, resisted P450-mediated metabolism, and exhibited negligible cytotoxicity. Two optimized compounds, YOK24 and NS-181, achieved complete resolution of amebic liver abscess in hamsters after both subcutaneous and oral administration. Together, these findings establish a general and broadly applicable strategy for the biosynthetic reprogramming of natural products, providing a blueprint for expanding the chemical and therapeutic space of complex metabolites beyond conventional synthetic and biosynthetic limits.

Metal-oxide interactions are ubiquitous in many technological applications and involve a complex interplay between the oxide support and the metal nanoparticle. Particularly, it has been proposed that in strong metal-support interaction, the defect chemistry affects the metal cluster morphology. Here we develop a physics-guided machine learning framework to decode these interactions using Pt₇ and Pt₁₃ representative of planar and tridimensional clusters, analyzing the impact of across oxygen vacancy concentrations of CeO_2-x = 0-12.5% (528 configurations). Our models (R² > 0.97) reveal that polaron swarms, rather than defect concentrations, predominantly control cluster shape and charge through size-dependent pathways. The framework yields quantitative design principles for defect-driven catalyst optimization and provides a general methodology for systematic mechanisms of metal-support interactions across diverse catalyst systems.

The orthorhombic tri-tin tetraoxide (Sn₃O₄) is a newly discovered polymorph and has attracted great attention due to its visible-light absorption capability. To improve performance and broaden the material space based on orthorhombic Sn₃O₄, impurity doping represents a promising approach. In this study, we predict stable cation-doped orthorhombic Sn₃O₄ crystals using machine learning interatomic potential (MLIP) calculations. Several candidate cations such as boron (B), aluminum (Al), strontium (Sr), and yttrium (Y) have been predicted as stable dopants in orthorhombic Sn₃O₄ with low Gibbs energies of formation. Based on this prediction, we synthesized cation-doped Sn₃O₄ powder samples using a hydrothermal method. We confirmed that the cations predicted to be stable by the MLIP could be synthesized into the orthorhombic powder phase. Among the samples, the Al-doped Sn₃O₄ powder exhibited superior photocatalytic hydrogen production activity under visible light. Furthermore, we fabricated thin films of Al-doped Sn₃O₄ and optimized the doping amount of Al to achieve high photocatalytic activity. The 5% Al-doped Sn₃O₄ exhibited the highest activity owing to its high crystallinity and optimal morphology for better separation of photogenerated carriers. The Al-doped orthorhombic Sn₃O₄ is promising for application as a visible light-active photocatalyst.

Electron transport across interfaces governs a broad range of fundamental phenomena. Although orbital overlap is recognized as a key determinant, its experimental quantification remains elusive. Here, we establish the interfacial hopping integral (t_eld-mol), quantifying orbital overlap between contacting atoms, as a predictive descriptor of single-molecule conductance in a benchmark domain of saturated α,ω-functionalized alkane junctions. Using scanning tunneling microscopy and molecular-junction mapping technique, we correlate conductance with molecular tilt (tilt_mol) across π- and σ-type headgroups to extract t_eld-mol. We start with single-atom-thick bismuth and lead adlayers on gold, with dominant p-character simpler than gold's d-orbitals. A tight-binding model incorporating Newns-Anderson-Grimley theory yields conductance heatmaps that qualitatively match experiment results and generalize to diverse molecular junctions. Applying this model to the seminal case of alkanedithiols rationalizes literature findings of one to three conductance sets by linking them to tilt_mol and corresponding t_eld-mol variations.

Proton-coupled electron transfer (PCET) governs many redox transformations, but is thermodynamically constrained when proton and electron transfer occur at a single site. Here, we introduce a new multisite PCET (MS-PCET) platform, based on the Keggin-type polyoxotungstate, [VW₁₂O₄₀]^3- (VW₁₂). Pairing VW₁₂ with either Brønsted bases or acids yields reagent pairs with tunable effective bond dissociation free energies (BDFE_eff) over 15 kcal mol^-1, enabling both oxidative and reductive H atom transfer reactions. Kinetic studies on the oxidative pathway by using 2,4,6-^tBu₃PhOH as a model hydrogen atom (H atom) donor reveal a product-like, entropy-dominated concerted proton-electron transfer (CPET) pathway from a preorganized hydrogen-bonded complex. By contrast, reductive H atom transfer reactions exhibit larger ΔH^‡ values, measurable kinetic isotope effects, and balanced Brønsted slope, consistent with synchronous CPET-type mechanism. Extension to N-H, O-H, and C-H substrates demonstrates the versatility of the VW₁₂ MS-PCET platform for tunable (de)hydrogenation.

We report the direct piezoelectric response of four deep eutectic solvents (DESs): choline chloride:ethylene glycol (ChCl:EG), choline chloride:glycerol (ChCl:Gly), choline chloride:1,3-propanediol (ChCl:PD), and choline chloride:urea (ChCl:urea). Measurement of current as a function of applied force produces a linear relationship from which the piezoelectric coefficient (d₃₃) was determined. The piezoelectric effect has previously been observed in room-temperature ionic liquids (RTILs), attributable to a pressure-induced liquid-to-crystalline solid phase transition. The observation of this phenomenon in DESs is unprecedented and underscores its generality. The magnitude of d₃₃ in these DESs is similar to that for RTILs, suggesting the potential to tune the piezoelectric response through careful selection of the DES constituents and constituent ratios.

ortho-Diacylbenzenes serve as versatile precursors for pharmaceutical synthesis, other biological applications, and organic synthesis. The intermolecular cyclization between the alkyl chains of two ketone substrates for the synthesis of ortho-diacylbenzenes offers atom-economical access to ortho-diacylbenzenes. However, intermolecular cyclization between the alkyl chains of two ketone substrates is a challenging chemical transformation. Here, we report that the copper-catalyzed reaction between ketone substrates containing alkyl chains in the presence of TEMPO as the oxidant undergoes dehydrogenation-initiated intermolecular [4 + 2] cyclization between the alkyl chains of two ketone substrates to regioselectively produce the ortho-diacylbenzene with high functional group tolerance. This copper-catalyzed intermolecular cyclization between the alkyl chains of two ketone substrates enables ketone substrates containing diverse molecular scaffolds to serve as efficient substrates for the synthesis of ortho-diacylbenzenes, although butyl-phenyl-ketones containing substituents at the δ-positions of the butyl chains regioselectively produce meta-diacylbenzene products. Consequently, structurally complex ketones generated from natural products or bioactive compounds undergo targeted transformation to efficiently produce ortho-diacylbenzenes. Interestingly, this copper-catalyzed intermolecular cyclization between the alkyl chains of two ketone substrates proceeds through the electrophilic TEMPO-catalyzed unknown [4 + 2] cycloaddition of two electron-poor alkenyl ketone intermediates, which overcomes the general requirement of the Diels-Alder cycloaddition reactions.

Multibridged azapyrenophanes were synthesized as organic circularly polarized luminescence (CPL) emitters. The g_lum reached +0.12 and the B_CPL amounted to 2,600 M^-1 cm^-1 at -95 °C. The xylylene-bridging to the binaphthyl-bridged pyrenophane produced a quadruply bridged structure that prompted the pyrene excimer to adopt a D₂-symmetric rigid conformation. This strategy maximized the latent CPL performance. Furthermore, these emitters functioned as temperature- and acid/base-triggered (+)/(-)- or on/off-CPL switches in which enantiospecific responses toward chiral solvents were also observed.