ACS Combinatorial Science最新文献

Cuproptosis, a recently identified form of copper-dependent cell death, shows promising tumor suppressive effects with minimal drug resistance. However, its therapeutic efficacy is hampered by its dependence on copper ions and the glutathione (GSH)-rich microenvironment in tumors. Here, we have developed polyvalent aptamer nanodrug conjugates (termed CuPEs@PApt) with a nucleosome-like structure to improve tumor cuproptosis therapy by exploiting mitochondrial copper overload and GSH depletion. Polyvalent aptamer (PApt), comprising polyvalent epithelial cell adhesion molecule aptamers for tumor targeting and repetitive PolyT sequences for copper chelation, facilitates efficient loading and targeted delivery of copper peroxide-Elesclomol nanodots (CuPEs). Upon internalization by tumor cells, Elesclomol released from CuPEs@PApt accumulates copper ions in mitochondria to initiate cuproptosis, while lysosomal degradation of CuP nanodots generates exogenous Cu²⁺ and H₂O₂, triggering a Fenton-like reaction for GSH depletion to enhance cuproptosis. In vitro and in vivo experiments confirm the efficacy of this strategy in inducing tumor cell cuproptosis and immunogenic cell death, the latter contributing to the activation of the antitumor immune response for synergistic tumor growth inhibition.

The direct utilization of carbon dioxide as an ideal one-carbon source in value-added chemical synthesis has garnered significant attention from the standpoint of global sustainability. In this regard, the photo/electrochemical reduction of CO₂ into useful fuels and chemical feedstocks could offer a great promise for the transition to a carbon-neutral economy. However, challenges in product selectivity continue to limit the practical application of these systems. A robust and general method for the conversion of CO₂ to the polarity-reversed carbon dioxide radical anion, a C1 synthon, is critical for the successful valorization of CO₂ to selective carboxylation reactions. We demonstrate herein a hydride and hydrogen atom transfer synergy driven general catalytic platform involving CO₂^•– for highly selective anti-Markovnikov hydrocarboxylation of alkenes via triple photoredox, hydride, and hydrogen atom transfer catalysis. Mechanistic studies suggest that the synergistic operation of the triple catalytic cycle ensures a low-steady-state concentration of CO₂^•– in the reaction medium. This method using a renewable light energy source is mild, robust, selective, and capable of accommodating a wide range of activated and unactivated alkenes. The highly selective nature of the transformation has been revealed through the synthesis of hydrocarboxylic acids from the substrates bearing a hydrogen atom available for intramolecular 1,n-HAT process as well as diastereoselective synthesis. This technology represents a general strategy for the merger of in situ formate generation with a synergistic photoredox and HAA catalytic cycle to provide CO₂^•– for selective chemical transformations.

In a photocatalysis process, quick charge recombination induced by small electron polarons in a photocatalyst and sluggish kinetics of hole transfer at the solid–liquid interface have greatly limited photocatalytic efficiency. Herein, we demonstrate hydrated transition metal ions as mediators that can simultaneously accelerate small electron polaron dissociation (via metal ion reduction) and hole transfer (through high-valence metal production) at the solid–liquid interface for improved photocatalytic pollutant degradation. Fe³⁺, by virtue of its excellent redox ability as a homogeneous mediator, enables the BiVO₄ photocatalyst to achieve drastically increased photocatalytic degradation performance, up to 684 times that without Fe³⁺. The enhanced performance results from Fe(IV) species production (via Fe³⁺ oxidation) induced by dissociation of small electron polarons (via Fe³⁺ reduction), featuring an extremely low kinetic barrier (5.4 kJ mol^–1) for oxygen atom transfer thanks to the donor–acceptor orbital interaction between Fe(IV) and organic pollutants. This work constructs a high-efficiency artificial photosynthetic system through synergistically eliminating electron localization and breaking hole transfer limitation at the solid–liquid interface for constructing high-efficiency artificial photosynthetic systems.

Quantum technologies would benefit from the development of high-performance quantum defects acting as single-photon emitters or spin-photon interfaces. Finding such a quantum defect in silicon is especially appealing in view of its favorable spin bath and high processability. While some color centers in silicon have been emerging in quantum applications, there remains a need to search for and develop new high-performance quantum emitters. By searching a high-throughput computational database of more than 22,000 charged complex defects in silicon, we identify a series of defects formed by a group III element combined with carbon ((A–C)_Si with A = B, Al, Ga, In, Tl) and substituting on a silicon site. These defects are analogous structurally, electronically, and chemically to the well-known T center in silicon ((C–C–H)_Si), and their optical properties are mainly driven by an unpaired electron on the carbon p orbital. They all emit in the telecom, and some of these color centers show improved properties compared to the T center in terms of computed radiative lifetime, emission efficiency, or smaller optical linewidth. The kinetic barrier computations and previous experimental evidence show that these T center-like defects can be formed through the capture of a diffusing carbon by a substitutional group III atom. We also show that the synthesis of hydrogenated T center-like defects followed by a dehydrogenation annealing step could facilitate the formation of these defects. Our work motivates further studies on the synthesis and control of this new family of quantum defects and demonstrates the use of high-throughput computational screening to discover new color center candidates.

A mechanism for the concerted pathway of coupled electron- and phase-transfer reactions (CEPhT) is proposed. CEPhT at three-phase interfaces formed by a solid electrode, an insulating organic solvent, and an aqueous electrolyte is driven by electric double layer (EDL) spillover, with significant electrostatic potential gradients extending a few nanometers into the insulating phase. This EDL spillover phenomenon is studied using scanning electrochemical cell microscopy to interrogate the oxidation of ferrocene in toluene to ferrocenium in water, (Fc)_tol → (Fc⁺)_aq + e^–. Finite element method simulations of the electrostatic potential distribution and species concentration profiles enable the calculation of complete i–E curves that incorporate mass transport, electron transfer, phase transfer, and the EDL structure. Simulated and experimental i–E traces show good agreement in the current magnitude and the effect of the supporting electrolyte, identifying an unexpected dependence of overall reaction kinetics on the concentration of the supporting electrolyte in the aqueous phase due to EDL spillover. An interfacial toluene/water mixing region generates a unique electrochemical microenvironment where concerted electron transfer and solvent shell replacement facilitate CEPhT. Kinetic expressions for concerted and sequential CEPhT mechanisms highlight the role of this interfacial environment in controlling the rate of CEPhT. These combined experimental and simulated results are the first to support a concerted mechanism for CEPhT where (Fc)_tol is transported to the interfacial mixing region at the three-phase interface, where it undergoes oxidation and phase transfer. EDL spillover can be leveraged for engineering sample geometries and electrostatic microenvironments to drive electrochemical reactivity in classically forbidden regions, e.g., insulating solvents and gases.

A robust method is described to synthesize degradable copolymers under aqueous miniemulsion conditions using α-lipoic acid as a cheap and scalable building block. Simple formulations of α-lipoic acid (up to 10 mol %), n-butyl acrylate, a surfactant, and a costabilizer generate stable micelles in water with particle sizes <200 nm. The ready availability of these starting materials facilitated performing polymerization reactions at large scales (4 L), yielding 600 g of poly(n-butyl acrylate-stat-α-lipoic acid) latexes that degrade under reducing conditions (250 kg mol^–1 → 20 kg mol^–1). Substitution of α-lipoic acid with ethyl lipoate further improves the solubility of dithiolane derivatives in n-butyl acrylate, resulting in copolymers that degrade to even lower molecular weights after polymerization and reduction. In summary, this convenient and scalable strategy provides access to large quantities of degradable copolymers and particles using cheap and commercially available starting materials.

Anomalous X-ray diffraction (AXD) and neutron diffraction can be used to crystallographically distinguish between metals of similar electron density. Despite the use of AXD for structural characterization in mixed metal clusters, there are no benchmark studies evaluating the accuracy of AXD toward assessing elemental occupancy in molecules with comparisons with what is determined via neutron diffraction. We collected resonant diffraction data on several homo and heterometallic clusters and refined their anomalous scattering components to determine metal site occupancies. Theoretical resonant scattering terms for Fe⁰, Co⁰, and Zn⁰ were compared against experimental values, revealing theoretical values are ill-suited to serve as references for occupancy determination. The cluster featuring distinct cation and anion metal compositions [CoCp₂*][(^tbsL)Fe₃(μ³–NAr)] was used to assess the accuracy of different f′ references for occupancy determination (f′_theoretical ± 15–17%; f′_experimental ± 10%). This methodology was applied toward calculating the occupancy of three different clusters: (^tbsL)Fe₂Zn(py) (6), (^tbsL)Fe₂Zn(μ³–NAr)(py) (7), and [CoCp*₂][(^tbsL)Fe₂Zn(μ³–NAr)] (8). The first two clusters maintain 100% Fe/Zn site isolation, whereas 8 showed metal mixing within the sites. The large crystal size of 8 enabled collection of neutron diffraction data which was compared against the results found with AXD. The ability of AXD to replicate the metal occupancies as determined by neutron diffraction supports the AXD occupancy methodology developed herein. Furthermore, the advantages innate to AXD (e.g., smaller crystal sizes, shorter collection times, and greater availability of synchrotron resources) versus neutron diffraction further support the need for its development as a standard technique.

Nitroaromatic compounds are found in brown carbon aerosols emitted to the Earth’s atmosphere by biomass burning, and are important organic chromophores for the absorption of solar radiation. Here, transient absorption spectroscopy spanning 100 fs–8 μs is used to explore the pH-dependent photochemical pathways for aqueous solutions of p-nitrophenol, chosen as a representative nitroaromatic compound. Broadband ultrafast UV–visible and infrared probes are used to characterize the excited states and intermediate species involved in the multistep photochemistry, and to determine their lifetimes under different pH conditions. The assignment of absorption bands, and the dynamical interpretation of our experimental measurements are supported by computational calculations. After 320 nm photoexcitation to the first bright state, which has ¹ππ* character in the Franck–Condon region, and ultrafast (∼200 fs) structural relaxation in the adiabatic S₁ state to a region with ¹nπ* electronic character, the S₁ p-nitrophenol population decays on a time scale of ∼12 ps. This decay involves competition between direct internal conversion to the S₀ state (∼40%) and rapid intersystem crossing to the triplet manifold (∼60%). Population in the T₁-state decays by excited-state proton transfer (ESPT) to the surrounding water and relaxation of the resulting triplet-state p-nitrophenolate anion to its S₀ electronic ground state in ∼5 ns. Reprotonation of the S₀-state p-nitrophenolate anion recovers p-nitrophenol in its electronic ground state. Overall recovery of the S₀ state of aqueous p-nitrophenol via these competing pathways is close to 100% efficient. The experimental observations help to explain why nitroaromatic compounds such as p-nitrophenol resist photo-oxidative degradation in the environment.

Photogenerated charge separation is pivotal for effecting efficient photocatalytic reactions. Understanding this process with spatiotemporal resolution is vital for devising highly efficient photocatalysts. Here, we employed pump–probe transient reflection microscopy to directly observe the temporal and spatial evolution of photogenerated electrons and holes on the surface of facet-engineered bismuth vanadate (BiVO₄) crystals. The findings suggest that the anisotropic built-in field of BiVO₄ crystals propels the separation of photogenerated electrons and holes toward different facets through a two-step process across varying time scales. Photogenerated electrons and holes undergo ultrafast separation within ∼6 ps, with electrons transforming into localized small polarons toward the {010} facets of truncated BiVO₄ octahedral crystals. However, the photogenerated holes prolong their separation up to ∼2000 ps in a drift–diffusion manner before ultimately accumulating on the {120} facets. This work provides a comprehensive visualization of spatiotemporal charge separation at the nano/microscale on semiconductor photocatalysts, which is beneficial for understanding the photocatalysis mechanism.

Dhilirane-type meroterpenoids (DMs) featuring a 6/6/6/5/5 ring system represent a rare group of fungal meroterpenoids. To date, merely 11 DMs have been isolated or derived, leaving their chemical diversity predominantly unexplored. Herein, we leverage an understanding of biosynthesis to develop a workflow for discovery of DMs by genome mining, metabolite analysis, and tailoring enzyme catalysis. Twenty-three new DMs, including seven unprecedented scaffolds, were consequently identified. An α-ketoglutarate (α-KG)-dependent oxygenase DhiD was found to catalyze the stereodivergent ring contraction of dhilirolide D to form the dhilirane skeleton; while the cytochrome P450 DhiH reshaped the structural diversity by establishing diverse C–C bonds and oxidation. Crystallographic and mutagenesis experiments provide a molecular basis for the DhiD reaction and its stereodivergent products. Notably, DhiD exhibits substrate-controlled catalytic versatility in the chemical expansion of DMs through ring contraction, hydroxylation, dehydrogenation, epoxidation, isomerization, epimerization, and α-ketol cleavage. Bioassay results demonstrated that the obtained meroterpenoids exhibited anti-inflammatory and insecticidal activities. Our work provides insight into nature’s arsenal for DM biosynthesis and the functional versatility of α-KG-dependent oxygenase and P450, which can be applied for target discovery and diversification of DM-type natural products.