ACS Combinatorial Science最新文献

Artificial transmembrane transport systems are receiving a great deal of attention for their potential therapeutic application. A major challenge is to switch their activity in response to environmental stimuli, which has been achieved mostly by modulating the binding affinity. We demonstrate here that the activity of a synthetic anion transporter can be controlled through changes in the membrane mobility and incorporation. The transporters─equipped with azobenzene photoswitches─poorly incorporate into the bilayer membrane as their thermally stable (E,E,E)-isomers, but incorporation is triggered by UV irradiation to give the (Z)-containing isomers. The latter isomers, however, are found to have a lower mobility and are therefore the least active transporters. This opposite effect of E-Z isomerization on transport capability offers unique photocontrol as is demonstrated by in situ irradiation studies during the used transport assays. These results help to understand the behavior of artificial transporters in a bilayer and are highly important to future designs, with new modes of biological activity and with the possibility to direct motion, which may be crucial toward achieving active transport.

Although intensive work on ammonia activation has been carried out in recent decades, generating nitrogen-centered radicals from NH₃ under ambient conditions remains quite challenging. In the presented research, the conversion of NH₃ to radical-like NH ligand has been achieved by the reactions of a series of dialkyl rare-earth (RE) complexes (1-RE, RE = Tb, Dy, Y, Ho, Er, Yb, and Lu) supported by β-diketiminate ligands with NH₃ in n-hexane at room temperature, resulting in the formations of the radical-like μ₃-NH ligands containing trinuclear RE complexes (2-RE). The radical-like feature of the μ₃-NH ligand was revealed by electron paramagnetic resonance and magnetic measurements, radical trapping experiments, and computational spin density analysis. In addition, H₂ was detected to form during the reaction of 1-RE with NH₃, indicating that the radical-like μ₃-NH ligand was likely to be generated via N–H bond homolysis. Moreover, the solvents and coordination pattern of β-diketiminate ligands are crucial for the formation of the radical-like μ₃-NH ligand from NH₃. When toluene instead of n-hexane was used in the reaction of 1-RE with NH₃, an array of octaamido tetranuclear RE complexes (3-RE) was obtained. The reaction of the dialkyl yttrium complex (4-Y) bearing a modified β-diketiminate ligand, in which the two mesityl substituents are replaced by a 2,6-diisopropylphenyl group and a 2-(dimethylamino)ethyl group, with NH₃ in both n-hexane and toluene only yielded a tetranuclear yttrium complex carrying the dianionic closed-shell μ₃-NH ligands (5-Y).

Plants contain a vast array of natural products yet to be discovered, particularly those minor bioactive constituents. Identification of these constituents requires a significant amount of plant material, presenting considerable technical challenges. Mugwort (Artemisia argyi) is a widely recognized insect repellent herb, particularly renowned for its extensive usage during the Dragon Boat Festival in China, but the specific constituent responsible for its repellent activity remains unknown. Here, we employed a gene-directed in vitro mining approach to characterize mugwort terpene synthases (TPSs) systematically in a yeast expression system. Based on the establishment of “Terpene synthase-standard library”, we have successfully identified 54 terpene products, including a novel compound designated as cyclosantalol. Through activity screening, we have identified that (+)-intermedeol, which presents in trace amount in plants, exhibits significant repellent activity against mosquitoes and ticks. After establishing its safety and efficacy, we then achieved its biosynthetic production in a yeast chassis, with an initial yield of 2.34 g/L. The methodology employed in this study not only identified a highly effective, safe, and commercially viable insect repellent derived from mugwort but also holds promise for uncovering and producing other valuable plant natural products in future research endeavors.

The increasing use of Metal–Organic Frameworks (MOFs) in separation, catalysis, or storage is linked to the targeted modification of their composition or porosity metrics. While modification of pore shape and size necessarily implies the assembly of alternative nets, compositional changes often rely on postsynthetic modification adapted to the functionalization or exchange of the organic linker or the modification of the inorganic cluster by metal exchange methods. We describe an alternative methodology that enables the integration of both types of modification, structural and compositional, in titanium MOFs by metal exchange reaction of the heterometallic cluster Ti₂Ca₂. A systematic analysis of this reactivity with MUV-10 is used to understand which experimental variables are crucial to enable replacement of calcium only or to integrate metal exchange with structural transformation. The isoreticular expanded framework, MUV-30, is next used to template the formation of MUV-301, a titanium framework not accessible by direct synthesis that displays the largest mesoporous cages reported to date. Given that the interest of Ti MOFs in photoredox applications often meets the limitations imposed by the challenges of titanium solution chemistry to design concrete candidates, this soft strategy based on preassembled frameworks will help integrate specific combinations of metals into high porosity architectures.

Organofluorine compounds, including fluorinated pyridines and isoquinolines, play a crucial role in pharmaceuticals, agrochemicals, and materials science. However, step-economic selective C–H-functionalization to access these fluorinated azaarenes is still underexplored, with selective meta-C–H-fluorination proving to be especially elusive. Here we present a practical method for formal meta-C–H-fluorination of pyridines and isoquinolines. By applying an oxazinoazaarene-based temporary pyridine dearomatization strategy with Selectfluor as an electrophilic F-source, fluorination of pyridines was achieved with exclusive C3-selectivity in moderate to good yields. The same strategy can also be applied to the formal meta-C–H-fluorination of isoquinolines. Late-stage-functionalization of drugs, drug precursors, and ligands as well as a large-scale one-pot dearomatization–fluorination–rearomatization reaction further demonstrate the synthetic utility of this approach.

Organic electrode materials (OEMs), composed of abundant elements such as carbon, nitrogen, and oxygen, offer sustainable alternatives to conventional electrode materials that depend on finite metal resources. The vast structural diversity of organic compounds provides a virtually unlimited design space; however, exploring this space through Edisonian trial-and-error approaches is costly and time-consuming. In this work, we develop a new framework, SPARKLE, that combines computational chemistry, molecular generation, and machine learning to achieve zero-shot predictions of OEMs that simultaneously balance reward (specific energy), risk (solubility), and cost (synthesizability). We demonstrate that SPARKLE significantly outperforms alternative black-box machine learning algorithms on interpolation and extrapolation tasks. By deploying SPARKLE over a design space of more than 670,000 organic compounds, we identified ≈5000 novel OEM candidates. Twenty-seven of them were synthesized and fabricated into coin-cell batteries for experimental testing. Among SPARKLE-discovered OEMs, 62.9% exceeded benchmark performance metrics, representing a 3-fold improvement over OEMs selected by human intuition alone (20.8% based on six years of prior lab experience). The top-performing OEMs among the 27 candidates exhibit specific energy and cycling stability that surpass the state-of-the-art while being synthesizable at a fraction of the cost.

Our recent study of 20 nanoporous activated carbons showed that a more disordered local carbon structure leads to enhanced capacitive performance in electrochemical double layer capacitors. Specifically, NMR spectroscopy measurements and simulations of electrolyte-soaked carbons evidenced that nanoporous carbons with smaller graphene-like domains have larger capacitances. In this study, we use Raman spectroscopy, a common probe of local structural disorder in nanoporous carbons, to test the disorder-driven capacitance theory. It is found that nanoporous carbons with broader D bands and smaller I_D/I_G intensity ratios exhibit higher capacitance. Most notably, the I_D/I_G intensity ratio probes the in-plane sizes of graphene-like domains and supports the findings from NMR that smaller graphene-like domains correlate with larger capacitances. This study supports our finding that disorder is a key metric for high capacitance in nanoporous carbons and shows that Raman spectroscopy is a powerful technique that allows rapid screening to identify nanoporous carbons with superior performance in supercapacitors.

The bottleneck of Li metal batteries toward practical applications lies at inferior cyclability as well as Li dendrite issues. As a promising solution, an interface engineering strategy is proposed herein for the Li anode through constructing a hybrid artificial interface. It is assembled onto the Li anode using photocontrolled free radical polymerization (photo-CRP) of polyethylene glycol diacrylate-hexafluorobutyl methacrylate and hexafluorobutyl methacrylate-trifluoroethyl carbonate (PEGDA-HFMBA@HFMBA-FEMC or PH@HF layer). Among such hybrid interfaces, the interior layer of PEGDA-HFMBA exists as a protective shield with flexibility and fracture resistance, while the exterior layer of HFMBA-FEMC plays a role as a LiF reservoir to promote Li mass transfer and its even electrodeposition. In the meantime, some excess HFMBA and FEMC monomers further dissolve into the electrolyte as molecular additives, followed by in situ generation of a thin and robust LiF-rich cathode electrolyte interface (CEI). With the resulting Li anode, Li/NCM811 full cells showcase multifold cyclability amplification in comparison to cells using Bare-Li, covering durable cyclability with a capacity retention of 81.8% after 400 cycles. When the cutoff voltage is elevated to 4.5 V or the working temperature is elevated to 45 °C, the cells still maintain a stable operation for extending 300 cycles.

Efficiently capturing fluorocarbons, potent greenhouse gases with high global warming potentials (GWP), remains a daunting challenge due to limited effective approaches for constructing high-performance adsorbents. To tackle this issue, we have pioneered a novel strategy of developing radical porous materials as effective adsorbents for fluorocarbon capture. The resulting radical covalent triazine framework (CTF), CTF-azo-R, shows exceptional fluorocarbon (perfluorohexane, a representative model pollutant among fluorocarbons) uptake capacity of 270 wt %, a record-high value among all porous materials reported to date. Spectral characteristics, experimental studies, and theoretical calculations indicate that the presence of stable radicals in CTF-azo-R contributes to its superior fluorocarbon capture performance. Furthermore, CTF-azo-R demonstrates exceptionally high chemical and thermal stabilities that fully meet the requirements for practical applications in diverse environments. Our work not only establishes radical CTF-azo-R as a promising candidate for fluorocarbon capture but also introduces a novel approach for constructing advanced fluorocarbon adsorbents by incorporating radical sites into porous materials. This strategy paves the way for the development of radical adsorbents, fostering advancements in both fluorocarbon capture and the broader field of adsorption and separation.

We report the development of an iterative Matteson homologation reaction with catalyst-controlled diastereoselectivity through the design of a new catalyst. This reaction was applied to the selective synthesis of each stereoisomer of benzestrol, a bioactive compound with estrogenic activity featuring three contiguous stereocenters. The different stereoisomers were assayed to determine their binding affinity for the estrogen receptor α (ERα), and the absolute configuration of the compound having uniquely high activity was determined. This research lays a framework for the catalytic synthesis and study of complete stereoisomeric sets of other bioactive molecules and chemical probes containing contiguous stereocenters.