December 3, 2024
Joining Natural and Synthetic DNA Using Biversal Nucleotides: Efficient Sequencing of Six-Nucleotide DNA
Bang Wang - ,
Hyo-Joong Kim - ,
Kevin M. Bradley - ,
Cen Chen - ,
Chris McLendon - ,
Zunyi Yang - , and
Steven A. Benner *
By rearranging hydrogen bond donor and acceptor groups within a standard Watson–Crick geometry, DNA can add eight independently replicable nucleotides forming four additional not found in standard Terran DNA. For many applications, the orthogonal pairing of standard and nonstandard pairs offers a key advantage. However, other applications require standard and nonstandard nucleotides to communicate with each other. This is especially true when seeking to recruit high-throughput instruments (e.g., Illumina), designed to sequence standard 4-nucleotide DNA, to sequence DNA that includes added nucleotides. For this purpose, PCR workflows are needed to replace nonstandard nucleotides in (for example) a 6-letter DNA sequence by defined mixtures of standard nucleotides built from 4 nucleotides. High-throughput sequencing can then report the sequences of those mixtures to bioinformatic alignment tools, which infer the original 6-nucleotide sequence by analysis of the mixtures. Unfortunately, the intrinsic orthogonality of standard and nonstandard nucleotides often demand polymerases that violate pairing biophysics to do this replacement, leading to inefficiencies in this “transliteration” process. Thus, laboratory in vitro evolution (LIVE) using “anthropogenic evolvable genetic information systems” (AEGIS), an important “consumer” of new sequencing tools, has been slow to be democratized; robust sequencing is needed to identify the AegisBodies and AegisZymes that AEGIS-LIVE delivers. This work introduces a new way to connect synthetic and standard molecular biology: biversal nucleotides. In an example presented here, a pyrimidine analogue (pyridine-2-one, y) pairs with Watson–Crick geometry to both a nonstandard base (2-amino-8-imidazo-[1,2a]-1,3,5-triazin-[8H]-4-one, P, the Watson–Crick partner of 6-amino-5-nitro-[1H]-pyridin-2-one, Z) and a base that completes the Watson–Crick hydrogen bond pattern (2-amino-2′-deoxyadenosine, amA). PCR amplification of GACTZP DNA with dyTP delivers products where Z:P pairs are cleanly transliterated to A:T pairs. In parallel, PCR of the same GACTZP sample at higher pH delivers products where Z:P pairs are cleanly transliterated to C:G pairs. By allowing robust sequencing of 6-letter GACTZP DNA, this workflow will help democratize AEGIS-LIVE. Further, other implementations of the biversal concept can enable communication across and between standard DNA and synthetic DNA more generally.
Copper(I)-Catalyzed Enantioselective α-Alkylation of 2-Acylimidazoles
Zong-Ci Liu - ,
Hong-Ming Zhang - ,
Yi Li - ,
Zi-Qing Wang - , and
Liang Yin *
Catalytic asymmetric α-alkylation of simple carboxylic acid derivatives is a challenging issue due to the difficulties in achieving high catalytic efficiency and controlling the enantioselectivity. Herein, by using a copper(I)-(R)-DTBM-SEGPHOS complex as a catalyst and 2-acylimidazoles as pronucleophiles, a general method for the catalytic asymmetric α-alkylation of simple carboxylic acid derivatives is accomplished. Various alkyl electrophiles, including allyl bromides, benzyl bromides, propargyl bromide, and unactivated alkyl sulfonates, serve as efficient alkylation reagents. The reaction enjoys the advantages of an easy reaction protocol, good functional group tolerance, and high enantioselectivity. 2,4,6-Trimethylphenol is found as an effective additive to increase yields. Preliminary 1H NMR experiments indicate the precoordination of 2-acylimidazoles to a copper(I) catalyst, which might acidify the α-hydrogens of 2-acylimidazoles and allow facile generation of stabilized copper(I) enolates. Finally, the synthetic utility of the present method is demonstrated by the asymmetric formal synthesis of AZD2716, a potent secreted phospholipase A2 inhibitor.
Elemene Hydrogel Modulates the Tumor Immune Microenvironment for Enhanced Treatment of Postoperative Cancer Recurrence and Metastases
Jing Xian - ,
Fan Xiao - ,
Jianhua Zou - ,
Wei Luo - ,
Shiqi Han - ,
Ziwei Liu - ,
Yiquan Chen - ,
Qianru Zhu - ,
Meng Li - ,
Chuao Yu - ,
Qimanguli Saiding - ,
Wei Tao *- ,
Na Kong *- , and
Tian Xie *
As a representative active ingredient of traditional Chinese medicine (TCM) and a clinically approved anticancer drug, elemene (ELE) exhibits exciting potential in the antitumor field; however, appropriate drug formulations still need to be explored for specific diseases such as postoperative cancer recurrence and metastasis. Herein, we report an ELE hydrogel with controlled drug release kinetics that can allow ELE to maintain effective concentrations at local lesion sites for extended periods to enhance the bioavailability of ELE. Concretely, dopamine-conjugated hyaluronic acid is synthesized and utilized to prepare ELE nanodrug-embedded hydrogels. In a model of postoperative breast cancer recurrence and metastasis, the ELE hydrogel demonstrates a 96% inhibition rate of recurrence; in contrast, the free ELE nanodrug shows only a 65.5% inhibition rate of recurrence. Importantly, the ELE hydrogel markedly stimulates a potent antitumor immune response in the microenvironment of cancer lesions, increasing antitumor immune cells such as CD8+ T cells, CD4+ T cells, and M1-type macrophages, as well as elevating antitumor cytokines including TNF-α, IFN-γ, and IL-6. Overall, this study not only advances the field of TCM but also highlights the transformative impact of controlled-release hydrogels in improving antitumor therapy.
December 2, 2024
Cooperative Atomically Dispersed Fe–N4 and Sn–Nx Moieties for Durable and More Active Oxygen Electroreduction in Fuel Cells
Fan Xia - ,
Bomin Li - ,
Bowen An - ,
Michael J. Zachman - ,
Xiaohong Xie - ,
Yiqi Liu - ,
Shicheng Xu - ,
Sulay Saha - ,
Qin Wu *- ,
Siyuan Gao - ,
Iddrisu B. Abdul Razak - ,
Dennis E. Brown - ,
Vijay Ramani - ,
Rongyue Wang - ,
Tobin J. Marks - ,
Yuyan Shao *- , and
Yingwen Cheng *
One grand challenge for deploying porous carbons with embedded metal–nitrogen–carbon (M–N–C) moieties as platinum group metal (PGM)-free electrocatalysts in proton-exchange membrane fuel cells is their fast degradation and inferior activity. Here, we report the modulation of the local environment at Fe–N4 sites via the application of atomic Sn–Nx sites for simultaneously improved durability and activity. We discovered that Sn–Nx sites not only promote the formation of the more stable D2 FeN4C10 sites but also invoke a unique D3 SnNx–FeIIN4 site that is characterized by having atomically dispersed bridged Sn–Nx and Fe–N4. This new D3 site exhibits significantly improved stability against demetalation and several times higher turnover frequency for the oxygen reduction reaction (ORR) due to the shift of the reaction pathway from a single-site associative mechanism to a dual-site dissociative mechanism with the adjacent Sn site facilitating a lower overpotential cleavage of the O–O bond. This mechanism bypasses the formation of the otherwise inevitable intermediate that is responsible for demetalation, where two hydroxyl intermediates bind to one Fe site. As a result, a mesoporous Fe/Sn-PNC catalyst exhibits a positively shifted ORR half-wave potential and more than 50% lower peroxide formation. This, in combination with the stable D3 site and enriched D2 Fe sites, significantly enhanced the catalyst’s durability as demonstrated in membrane electrode assemblies using complementary accelerated durability testing protocols.
A Dual-Target and Dual-Mechanism Design Strategy by Combining Inhibition and Degradation Together
Yongbo Liu - ,
Xiuyun Sun *- ,
Qianlong Liu - ,
Chi Han - , and
Yu Rao *
Glioblastoma, a highly aggressive brain tumor, lacks effective treatment with low 5 year survival rates. Urgency for new therapies is evident. Mammalian targets of rapamycin (mTOR) and G1 to S phase transition 1 gene (GSPT1) are overexpressed in glioblastoma, regulating vital cellular functions. Current mTOR inhibitors face challenges in clinical efficacy and drug resistance. Similarly, GSPT1-targeting therapies have not progressed of glioblastoma in clinical trials. Research studies suggested that combining mTOR inhibition with GSPT1 degradation may overcome resistance and enhance efficacy. We propose the concept of jointly implementing inhibition and degradation on different proteins, integrating the properties of inhibitors and degraders into the same molecule. Introducing YB-3–17, a novel bifunctional molecule, robustly inhibits mTOR and selectively degrades GSPT1. As a tool compound for proof-of-concept studies, YB-3–17 sharpens selectivity, avoiding off-target effects, and selectively induces GSPT1 degradation and mTOR inhibition, showing superior efficacy in tumor cell lines compared to that of standalone therapies. RNA-seq analysis highlights the advantages of YB-3-17 over mTOR inhibitor treatment. YB-3–17 can safely and effectively inhibit tumor growth in mice, offering a promising direction for precision treatment of glioblastoma, representing the first attempt to combine mTOR inhibition with GSPT1 degradation. This work also demonstrates that it is conceptually possible to successfully combine the properties of small molecule inhibitors and degraders into a single molecule, killing two birds with one stone.
Closed-Loop Chemical Recycling of a Biobased Poly(oxanorbornene-fused γ-butyrolactone)
Eva Harsevoort - ,
Răzvan C. Cioc - ,
Martin Lutz - ,
Arnaud Thevenon *- , and
Pieter C. A. Bruijnincx *
This publication is Open Access under the license indicated. Learn More
New polymers, properly designed for end-of-life and efficiently formed from renewable carbon, are key to the transition to a more sustainable circular plastics economy. Ring-opening polymerization (ROP) of bicyclic lactones is a promising method for the production of intrinsically recyclable polyesters, but most lactone monomers lack an efficient synthesis route from biobased starting materials, even though this is essential to sustainably account for material loss during the life cycle. Herein, we present the exceptionally rapid and controlled polymerization of a fully biobased tricyclic oxanorbornene-fused γ-butyrolactone monomer (M1). Polyester P(M1) was formed in low dispersity (D̵ = 1.2–1.3) and controllable molecular weight up to Mn = 76.8 kg mol–1 and exhibits a high glass transition temperature (Tg = 120 °C). The orthogonal olefin and lactone functionalities offer access to a wide range of promising materials, as showcased by postpolymerization modification by hydrogenation of the olefin, which increased polymer thermal stability by over 100 °C. Next to rapid hydrolytic degradation and solvolysis, the poly(oxanorbornene-fused γ-butyrolactone) could be cleanly chemically recycled back to the monomer (CRM), in line with its favorable ceiling temperature (Tc) of 73 °C. The density functional theory (DFT)-computed ΔH° of ring-opening with methanol of γ-butyrolactone-based monomers provided a model to predict Tc, and the DFT-computed and X-ray crystal structure-derived structural parameters of M1, hydrogenated analogue M1-H2, and regioisomer M2 offered insights into the structural descriptors that cause the high polymerizability of M1, which is key to establishing structure–property relations.
Determining Covalent Organic Framework Structures Using Electron Crystallography and Computational Intelligence
Xiangyu Zhang - ,
Junyi Hu - ,
Huiyu Liu - ,
Tu Sun - ,
Zidi Wang - ,
Yingbo Zhao - ,
Yue-Biao Zhang - ,
Ping Huai - ,
Yanhang Ma *- , and
Shan Jiang *
The structural characterization of new materials often poses immense challenges, especially when obtaining single-crystal structures is difficult, which is a common difficulty with covalent organic frameworks (COFs). Despite this, understanding the atomic structure is crucial as it provides insights into the arrangement and connectivity of organic building blocks, offering the opportunity to establish the correlation of structure–function relationships and unravel material properties. In this study, we present an approach for determining the structures of COFs, an integration of electron crystallography and computational intelligence (COF+). By applying established chemistry knowledge and employing particle swarm optimization (PSO) for trial structure generation, we overcome existing limitations, thus paving the way for advancements in COF structural determination. We have successfully implemented this technique on four representative COFs, each with unique characteristics. These examples underline the accuracy and efficacy of our approach in addressing the challenges tied to COF structural determination. Furthermore, our approach has revealed new structure candidates with different topologies or interpenetrations that are chemically feasible. This discovery demonstrates the capability of our algorithm in constructing trial COF structures without being influenced by topological factors. Our new approach to COF structure determination represents a significant advancement in the field and opens new avenues for exploring the properties and applications of COF materials.
Irreversible Lattice Expansion Effects in Nanoscale Indium Oxide for CO2 Hydrogenation Catalysis
Chenyue Qiu - ,
Junchuan Sun - ,
Mengsha Li - ,
Chengliang Mao - ,
Rui Song - ,
Zeshu Zhang - ,
Doug D. Perovic - ,
Jane Y. Howe *- ,
Lu Wang *- , and
Geoffrey A. Ozin *
Thermal energy has been considered the exclusive driving force in thermochemical catalysis, yet associated lattice expansion effects have been overlooked. To shed new light on this issue, variable temperature in situ high-resolution (scanning) transmission electron microscopy (HR-(S)TEM) and electron energy-loss spectroscopy (EELS) were employed to provide detailed information on the structural changes of an archetype nanoscale indium oxide materials and how these effects are manifest in reverse water gas shift heterogeneous catalytic reactivity. It is found that with increasing temperature and vacuum conditions, an irreversible surface lattice expansion is traced to the formation and migration of oxygen vacancies. Together, these changes are believed to be responsible for the decreased activation energy and improved reaction rate observed for the reverse water gas shift reaction. Studies of this kind provide new insight into how thermal energy affects thermochemical heterogeneous catalysis.
Upcycling of Polystyrene to Aromatic Polyacids by Tandem Friedel–Crafts and Oxidation Reactions
Nikolaos S. Giakoumakis - ,
Carlos Marquez - ,
Rodrigo de Oliveira-Silva - ,
Dimitrios Sakellariou - , and
Dirk E. De Vos *
Due to the high demand and the increasing production rate of plastic materials, vast amounts of wastes are generated every year. An important fraction of these wastes contain polystyrene (PS), which is seldom recycled, neither mechanically nor chemically. While several chemical recycling strategies have been developed, they are either very energy-demanding or produce chemicals that can hardly be employed in the synthesis of plastics (e.g., benzene and benzoic acid). Here, we report the upcycling of PS waste into aromatic polyacids, useful in polyester synthesis, such as polyethylene terephthalate (PET). To this end, a conventional Friedel–Crafts acylation was first investigated, to produce an acylated PS chain, using acetic anhydride and stoichiometric amounts of AlCl3. As a catalytic alternative, the alkylation of PS was studied, using InCl3 and isopropyl acetate. The acylated and alkylated PS samples were then oxidized to produce terephthalic (TA), isophthalic (IPTA), benzoic (BA), and trimesic (TMA) acid.
Boosting Enzyme-like Activities via Atomization of Cerium for Tumor Microenvironment-Responsive Cascade Therapy
Mengdie Jin - ,
Zhong Liang - ,
Yongkang Huang - ,
Mengzhen Zhang - ,
Hao Fu - ,
Biao Wang - ,
Jialiang Guo - ,
Qiang Yang - ,
Huayi Fang - ,
Jin-Cheng Liu - ,
Xinyun Zhai *- ,
Chun-Hua Yan - , and
Yaping Du *
Nanozyme catalytic therapeutic efficacy is limited by the finite enzyme activity and specificity. In this work, nitrogen-doped carbon loaded with a cerium single-atom nanozyme (Ce SAs@NC) is synthesized, exhibiting tumor specificity and excellent multiple enzyme-like activities. Compared with nitrogen-doped carbon loaded with CeO2 nanoparticles, Ce SAs@NC shows excellent peroxidase-like and catalase-like activity. Ce SAs@NC can convert intracellular hydrogen peroxide into cytotoxic hydroxyl radical and O2, which can be further transferred to superoxide radicals. Cascade enzyme reactions not only alleviate the hypoxic microenvironment of tumors but also induce lipid peroxidation and apoptosis or necrosis of tumor cells. The mild photothermal action will enhance the enzyme-like activities of Ce SAs@NC rather than induce the production of heat shock proteins to protect tumor cells. In addition, Ce SAs@NC can regulate the immune environment, stimulate M1 macrophages to trigger immune responses, and inhibit tumor proliferation. Thanks to the combination of the size effect of the single atoms, photothermal influence, multiple enzyme-like activities, and immunological effect, the Ce SAs@NC platform appears to have tumor specificity, less toxic side effects, and a high curative effect both in vitro and in vivo.
Surface Structure Dependent Activation of Hydrogen over Metal Oxides during Syngas Conversion
Bing Bai - ,
Yihan Ye - ,
Feng Jiao *- ,
Jianping Xiao - ,
Yang Pan - ,
Zehua Cai - ,
Mingshu Chen - ,
Xiulian Pan *- , and
Xinhe Bao
Despite the extensive studies on the adsorption and activation of hydrogen over metal oxides, it remains a challenge to investigate the structure-dependent activation of hydrogen and its selectivity mechanism in hydrogenation reactions. Herein we take spinel and solid solution MnGaOx with a similar bulk chemical composition and study the hydrogen activation mechanism and reactivity in syngas conversion. The results show that MnGaOx-Solid Solution (MnGaOx-SS) is a typical Mn-doped hexagonal close-packed (HCP) Ga2O3 with a Ga-rich surface. Upon exposure to hydrogen, Ga–H and O–H species are simultaneously generated. Ga–H species are highly active but unselective in CO activation, forming CHxO, and ethylene hydrogenation, forming ethane. In contrast, MnGaOx-Spinel is a face-centered-cubic (FCC) spinel phase featuring a Mn-rich surface, thus effectively suppressing the formation of Ga–H species. Interestingly, only part of the O–H species are active for CO activation while the O–H species are inert for olefin hydrogenation over MnGaOx-Spinel. Therefore, MnGaOx-Spinel exhibits a higher activity and higher light-olefin selectivity than MnGaOx-SS in combination with SAPO-18 during syngas conversion. These fundamental understandings are essential to guide the design and further optimization of metal oxide catalysts for selectivity control in hydrogenations.
Total Synthesis of Euphorbialoid A
Junichi Taguchi - ,
Shintaro Fukaya - ,
Haruka Fujino - , and
Masayuki Inoue *
Euphorbialoid A (1) belongs to the rare diterpenoid family of premyrsinanes and exhibits potent anti-inflammatory effects. The 5/7/6/3-membered carbocycle (ABCD-ring) of 1 contains 11 contiguous stereocenters and seven oxygen-containing functional groups. Moreover, four of the six hydroxy groups of 1 are concentrated in the southern sector and flanked by four structurally different acyl groups. The dense array of various functional groups with disparate reactivities on the tetracyclic ABCD-ring presents a daunting challenge for the chemical synthesis of 1. As a reflection of its formidable complexity, synthesis of 1 or any other premyrsinane diterpenoids has not yet been reported. Here, we devised a novel strategy comprising two stages and achieved the first total synthesis of 1 (35 steps as the longest linear sequence). In the first stage, the ABCD-ring was expeditiously assembled by integrating three powerful transformations: (1) Pt-doped TiO2-catalyzed radical coupling to attach a northern chain to a 6/3-membered CD-ring, (2) Pd-catalyzed decarboxylative asymmetric allylation to construct a quaternary carbon with a southern chain, and (3) a Co-mediated Pauson–Khand reaction to cyclize the two chains into the 5/7-membered AB-ring. In the second stage, three-dimensional structures of the ABCD-ring intermediates were utilized to stereoselectively fabricate the A-ring and site-selectively append the four different acyl groups. In the present total synthesis, we revealed the significance of orchestrating the multistep reaction sequence and incorporating cyclic protective groups. The overall strategy and tactics provide new insights into designing synthetic routes to premyrsinanes and densely oxygenated terpenoids decorated with diverse acyl groups.
Tuning of the Polymeric Nanofibril Geometry via Side-Chain Interaction toward 20.1% Efficiency of Organic Solar Cells
Jing Zhou - ,
Liang Wang - ,
Chenhao Liu - ,
Chuanhang Guo - ,
Chen Chen - ,
Yuandong Sun - ,
Yujie Yang - ,
Jingchao Cheng - ,
Zirui Gan - ,
Zhenghong Chen - ,
Wei Sun - ,
Jinpeng Zhou - ,
Weiyi Xia - ,
Dan Liu - ,
Wei Li - , and
Tao Wang *
Constructing fibril morphology has been believed to be an effective method of achieving efficient exciton dissociation and charge transport in organic solar cells (OSCs). Despite emerging endeavors on the fibrillization of organic semiconductors via chemical structural design or physical manipulation, tuning of the fibril geometry, i.e., width and length, for tailored optoelectronic properties remains to be studied in depth. In this work, a series of alkoxythiophene additives featuring varied alkyl side chains connected to thiophene are designed to modulate the growth of fibril aggregates in cutting-edge polymer donors PM6 and D18. Molecular dynamics simulations and morphological characterizations reveal that these additives preferentially locate near and entangle with the side chains of polymer donors, which enhance the conjugated backbone stacking of polymer donors to form nanofibrils with the width expanding from 12.6 to 21.8 nm and the length increasing from 98.3 to 232.7 nm. This nanofibril structure is feasible to acquire efficient exciton dissociation and charge transport simultaneously. By integrating the fibril PM6 and L8-BO as the donor and acceptor layers in pseudo-bulk heterojunction (p-BHJ) OSCs via layer-by-layer deposition, an improvement of power conversion efficiency (PCE) from 18.7% to 19.8% is observed, contributed by enhanced light absorption, charge transport, and reduced charge recombination. The versatility of these additives is also verified in D18:L8-BO OSCs, with enhanced PCE from 19.3% to 20.1%, which is among the highest values reported for OSCs.
December 1, 2024
Intricate Low-Symmetry Ag6L4 Capsules Formed by Anion-Templated Self-Assembly of the Stereoisomers of an Unsymmetric Ligand
Shohei Tashiro *- ,
Yoshihiko Yamada - ,
Lea Antonia Kringe - ,
Yoshiki Okajima - , and
Mitsuhiko Shionoya *
This publication is Open Access under the license indicated. Learn More
Metal–organic cages and capsules exhibit space-specific functions based on their discrete hollow structures. To acquire enzyme-like asymmetric or intricate structures, they have been modified by desymmetrization with two or more different ligands. There is a need to establish new strategies that can desymmetrize structures in a simple way using only one type of ligand, which is different from the mixed-ligand approach. In this study, a strategy was developed to form interconvertible stereoisomers using the unsymmetric macrocyclic ligand benzimidazole[3]arene. Single-crystal X-ray diffraction analysis revealed that the isomers assembled with silver tetrafluoroborate afforded a conformationally heteroleptic Ag6L4 capsule with an intricate structure. The six Ag ions in the capsule were desymmetrized, resulting in significantly different coordination geometries. Remarkably, the capsule encapsulates a single tetrafluoroborate anion via multipoint C–H···F–B hydrogen bonds in both the solid and solution states, suggesting that anions of appropriate size and shape can act as a template for the capsule formation. These results demonstrate that the use of isomerizable and unsymmetric ligands is the effectiveness of constructing highly dissymmetric supramolecular structures from a single ligand.
Wavelength-Dependent Dynamic Behavior in Thiol–Ene Networks Based on Disulfide Exchange
Bernhard Sölle - ,
Max Schmallegger - ,
Sandra Schlögl *- , and
Elisabeth Rossegger *
While latent catalysts have become a well-established strategy for locally and temporally controlling bond exchange reactions in dynamic polymer networks, there is a lack of inherently tailorable systems. Herein, we introduce a thiol–ene network based on disulfide exchange that alters its dynamic properties as a function of the color of light used during the curing reaction. For this purpose, selected allyl-bearing disulfides are synthesized, which are transparent at 450 nm but undergo disulfide scission upon 365 nm light irradiation, as confirmed by UV–vis and EPR measurements. Incorporated into a thiol–ene resin, the wavelength used in the curing reaction defines the dynamic properties of the obtained photopolymer. At 450 nm, photocuring yields a dynamic network with disulfide bonds, which relaxes to 63% of its original stress within 112 s at 160 °C (without the requirement of an external catalyst). In contrast, curing with 365 nm light induces disulfide scission yielding photopolymers, which contain predominately monosulfidic links. The permanent nature of the links effectively prevents relaxation of the polymer within a reasonable period of time, confirming the successful alteration of its dynamic properties simply by the color of the light source used.
November 30, 2024
Precisely Constructing Superlattices of Soft Giant Molecules via Regulating Volume Asymmetry
Huanyu Lei - ,
Xian-You Liu - ,
Yicong Wang - ,
Xing-Han Li - ,
Xiao-Yun Yan - ,
Tong Liu - ,
Jiahao Huang - ,
Weiyi Li - ,
Lichun Wang - ,
Xiaoyi Kuang - ,
Xiaran Miao - ,
Fenggang Bian - ,
Mingjun Huang - ,
Yuchu Liu *- , and
Stephen Z.D. Cheng *
Soft matters, particularly giant molecular self-assembly, have successfully replicated complex structures previously exclusive to metal alloys. These superlattices are constructed from mesoatoms─supramolecular spherical motifs of aggregated molecules, and the formation of superlattices critically depends on the volume distributions of these mesoatoms. Herein, we introduce two general methods to control volume asymmetry (i.e., the volumes’ ratio of the largest to smallest mesoatoms, VL/VS) within giant molecular self-assembly. Leveraging the spontaneous increase in the mesoatomic volume ratio in unary systems and self-sorted binary blends, we systematically adjust the volume asymmetry from 1.0 to 9.0 across 24 unary systems and 56 binary blends of giant molecules, uncovering the formation of various superlattices, including BCC, Frank-Kasper A15, σ, Laves C14, C15, NaZn13, AlB2, and notably, the first NaCl like superlattice in homogeneous soft matter self-assembly. A geometric-based analysis, combined with experimental results, further establishes a quantitative relationship between volume asymmetry and the corresponding superlattice formations, thus laying a solid foundation for superlattice engineering within giant molecular systems to mimic and even beyond metal alloys. The lattice parameters of various unit cells range from approximately 5 to 20 nm. Our investigation in giant molecules could guide the advancement of mesoscopic, periodic soft matter materials.
Gold/HNTf2-Cocatalyzed Asymmetric Annulation of Diazo-Alkynes: Divergent Construction of Atropisomeric Biaryls and Arylquinones
Yi-Bo Wang - ,
Wei Liu - ,
Ting Li - ,
Yazhu Lu - ,
Yi-Tian Yu - ,
Hai-Tao Liu - ,
Meiwen Liu - ,
Pengfei Li - ,
Peng-Cheng Qian *- ,
Hao Tang *- ,
Jia Guan - ,
Long-Wu Ye - , and
Long Li *
Due to the inherent challenges posed by the linear coordination of gold(I) complexes, asymmetric gold-catalyzed processes remain challenging, particularly in the atroposelective synthesis of axially chiral skeletons. Except for extremely few examples of intramolecular annulations, the construction of axial chirality via asymmetric gold-catalyzed intermolecular alkyne transformation is still undeveloped. Herein, a gold/HNTf2-cocatalyzed asymmetric diazo-alkyne annulation is developed, allowing the atroposelective and divergent synthesis of chiral non-C2-symmetric biaryls and arylquinones in generally good to excellent yield (up to 93% yield) and enantioselectivity (up to 99% ee), with broad substrate scope. Notably, this work represents the first gold-catalyzed atroposelective construction in an intermolecular manner. More interestingly, this strategy is successfully extended to the first asymmetric construction of seven-membered-ring atropisomers bearing one carbon-centered chirality in excellent diastereoselectivity and high enantioselectivity (up to 93% ee and 50:1 dr). Remarkably, the utility of this methodology is further illustrated by the successful application of a representative axially chiral ligand in a series of enantioselective reactions. Importantly, the Brønsted acid as a proton-shuttle cocatalyst significantly promotes this asymmetric annulation. Additionally, the origin of enantioselectivity of this annulation and the role of HNTf2 are disclosed by density functional calculations and control experiments.
Bioorthogonal Activation of Deep Red Photoredox Catalysis Inducing Pyroptosis
Jungryun Kim - ,
Yunjie Xu *- ,
Jong Hyeon Lim - ,
Jin Yong Lee *- ,
Mingle Li *- ,
Joseph M. Fox *- ,
Marc Vendrell *- , and
Jong Seung Kim *
The revolutionary impact of photoredox catalytic processes has ignited novel avenues for exploration, empowering us to delve into nature in unprecedented ways and to pioneer innovative biotechnologies for therapy and diagnosis. However, integrating artificial photoredox catalysis into living systems presents significant challenges, primarily due to concerns over low targetability, low compatibility with complex biological environments, and the safety risks associated with photocatalyst toxicity. To address these challenges, herein, we present a novel bioorthogonally activatable photoredox catalysis approach. In this approach, potent photocatalyst selection via atom replacement of the rhodamine core yielded the bioorthogonally activatable photocatalyst (PC-Tz). The introduction of 1,2,4,5-tetrazine quenched its photocatalytic properties, which were restored upon an intracellular inverse electron-demand Diels–Alder (iEDDA) reaction with trans-cyclooctene (TCO) localized in mitochondria. This reaction led to remarkable photocatalytic oxidation of nicotinamide adenine dinucleotide (NADH), effectively manipulating the mitochondrial electron transport chain (ETC) under hypoxic conditions in cancer cells. Additionally, photocatalytic pyroptotic cell death was observed through a caspase-3/gasdermin E (GSDME) pathway, achieving notable antitumor efficacy and adenosine triphosphate (ATP) reduction in tumor cells. To the best of our knowledge, this represents the first example of bioorthogonally activatable photoredox catalysis, opening new avenues for chemists to spatiotemporally control activity in specific cell organelles without disrupting other native biological processes.
Single-Crystal Dynamic Covalent Organic Frameworks for Adaptive Guest Alignments
Shan Liu - ,
Lei Wei - ,
Tengwu Zeng - ,
Wentao Jiang - ,
Yu Qiu - ,
Xuan Yao - ,
Qisheng Wang - ,
Yingbo Zhao - , and
Yue-Biao Zhang *
Dynamic 3D covalent organic frameworks (COFs) have shown a concerted structural transformation upon adaptive guest inclusion. However, the origin of the conformational mobility and the host–guest adaptivity remain conjecture of the pedal motions of revolving imine linkages, often without considering the steric hindrance from the interwoven frameworks. Here, we present atomic-level observation of the rotational and translational dynamics in single-crystal COF-300 upon adaptive guest inclusion of various organic molecules, featuring multiple rotamers of covalent linkages and switchable interframework noncovalent interactions. Specifically, we developed a diffusion gradient transimination protocol to facilitate the growth of COF single crystals, enabling a high-resolution X-ray diffraction structural analysis. We uncovered metastable and low-symmetry intermediate phases from contracted to expanded phases during structural evolution. We identified torsion angles in the terephthalaldehyde diimine motifs that switch from anti-periplanar to syn-periplanar/anticlinal conformations. Moreover, the rotational dynamics of the imine linkage were concurrent with the translational dynamics of tetraphenylmethane units, which tend to form the translational quadruple phenyl embrace. Such conformational mobility allows the frameworks to adapt to various guest molecules, such as alcohols, esters, phenols, and diols, featuring double linear, herringbone, zigzag chains, triple helix, and tubular alignments. Quantitative energy analyses revealed that such dynamic structure transformations are not arbitrary but follow specific pathways that resemble protein folding. The work is paving the way to developing robust, dynamic, and crystalline molecular sponges for studying the condensed structure of liquids without the need for further crystallization.
Above-Room-Temperature Ferromagnetism Regulation in Two-Dimensional Heterostructures by van der Waals Interfacial Magnetochemistry
Gaojie Zhang - ,
Hao Wu - ,
Li Yang - ,
Zheng Chen - ,
Wen Jin - ,
Bichen Xiao - ,
Wenfeng Zhang - ,
Changsheng Song *- , and
Haixin Chang *
Most methods for regulating physical and chemical properties of materials involve the breaking and formation of chemical bonds, which inevitably change local structures. Two-dimensional (2D) ferromagnets are critical for spintronic memory and quantum devices, but most of them maintain ferromagnetism at low temperature, and multiaspect control of 2D ferromagnetism at room temperature or above is still missing. Here, we report a nondestructive, van der Waals (vdW) interfacial magnetochemistry strategy for above-room-temperature, multiaspect 2D ferromagnetism regulation. By vdW coupling nonmagnetic MoS2, WSe2, or Bi1.5Sb0.5Te1.7Se1.3 with 2D vdW ferromagnet Fe3GaTe2, the Curie temperature is enhanced up to 400 K, best for 2D ferromagnets, with 26.8% tuning of room-temperature perpendicular magnetic anisotropy and an unconventional anomalous Hall effect up to 340 K. These phenomena originate from changes in magnetic exchange interactions and magnetic anisotropy energy by interfacial charge transfer and spin–orbit coupling. This work opens a pathway for engineering multifunctional 2D heterostructures by vdW interfacial magnetochemistry.
November 29, 2024
Ultrafast Cycloreversion of Thymine-Toluene [2 + 2] Cycloadducts by DNA Photolyase
Debanjana Chakraborty - ,
Chao Yang - ,
Jialong Jie - ,
Lijuan Wang - , and
Dongping Zhong *
DNA photolyases use blue light and fully reduced flavin cofactor to repair UV-induced cyclobutane pyrimidine dimers (CPD) formed between two adjacent thymine bases in DNA. Thymine can form [2 + 2] cyclobutane adducts with its biological isosteres like toluene upon UV irradiation, resulting in chemically different analogues of CPD. Here, we investigated the cycloreversion reactions of two such adducts formed between thymine and toluene, T<>Tol, catalyzed by a class-I CPD photolyase. The photolyase can bind to the T<>Tol adducts efficiently and restore the constituent bases upon excitation. Using femtosecond spectroscopy, we systematically characterized all the elementary steps involved in the enzymatic cycloreversion of the T<>Tol adducts and comprehensively analyzed the key intermolecular electron-transfer (ET) reactions and cyclobutane bond splitting steps. The initial electron injection to the bound adducts happens primarily through a two-step electron hopping mechanism, unlike in CPD repair where direct electron tunneling is dominant. After electron injection and ultrafast first-bond splitting, the delicate competition between the second bond splitting and a futile back ET dictates the overall reaction quantum yields of the adducts, influenced by the stability of adduct intermediates and steric crowding around the constituent bases. The final electron return for the cycloreversion reactions adopts a different pathway compared to CPD repair. The photolyase utilizes its conserved photorepair mechanism and allows ET pathway flexibility to reverse the [2 + 2] cycloaddition reaction of non-natural analogues of CPD.
Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation
Thomas C. Minshull - ,
Emily J. Byrd - ,
Monika Olejnik - , and
Antonio N. Calabrese *
This publication is Open Access under the license indicated. Learn More
Deposits of aggregated TAR DNA-binding protein 43 (TDP-43) in the brain are associated with several neurodegenerative diseases. It is well established that binding of RNA/DNA to TDP-43 can prevent TDP-43 aggregation, but an understanding of the structure(s) and conformational dynamics of TDP-43, and TDP-43-RNA complexes, is lacking, including knowledge of how the solution environment modulates these properties. Here, we address this challenge using hydrogen–deuterium exchange-mass spectrometry. In the presence of RNA olignoucleotides, we observe protection from exchange in the RNA recognition motif (RRM) domains of TDP-43 and the linker region between the RRM domains, consistent with nucleic acid binding modulating interdomain interactions. Intriguingly, at elevated salt concentrations, the extent of protection from exchange is reduced in the RRM domains when bound to an RNA sequence derived from the 3′ UTR of the TDP-43 mRNA (CLIP34NT) compared to when bound to a (UG)6 repeat sequence. Under these conditions, CLIP34NT is no longer able to prevent TDP-43 aggregation. This suggests that a salt-induced structural rearrangement occurs when bound to this RNA, which may play a role in facilitating aggregation. Additionally, upon RNA binding, we identify differences in exchange within the short α-helical region located in the C-terminal domain (CTD) of TDP-43. These allosterically altered regions may influence the ability of TDP-43 to aggregate and fine-tune its RNA binding repertoire. Combined, these data provide additional insights into the intricate interplay between TDP-43 aggregation and RNA binding, an understanding of which is crucial for unraveling the molecular mechanisms underlying TDP-43-associated neurodegeneration.
Biosynthesis-Encoded Lipogenic Acetyl-CoA Measurement Using NMR Reveals Glucose-Driven Lipogenesis and Glutamine’s Alternative Roles in Kidney Cancer
Sihyang Jo - ,
Munjun Seo - ,
Thi Ha Nguyen - ,
Jin Wook Cha - ,
Yong Jin An *- , and
Sunghyouk Park *
Fatty acid de novo synthesis (FADNS) is a critical process in lipogenesis that is characteristically altered in clear cell renal cell carcinoma (ccRCC), which is the major type of kidney cancer. An important challenge in studying the FADNS process has been the accurate measurement of cytosolic lipogenic acetyl-CoA (AcCoA), the precursor in FADNS, due to its compartmentalization within cells. Here, we describe a novel NMR-based method to decode the isotopic enrichment of lipogenic AcCoA, which, as we demonstrated, is encoded in the simple signal ratios of the geminal methyl groups of lanosterol during its biosynthesis. The approach was validated based on the independence of the tracer enrichment and species along with the expected FADNS modulation using differentially enriched tracers and a well-studied drug. Application of this technique to 786-O ccRCC cells showed that glucose may serve as a major carbon source for lipogenic AcCoA in FADNS at physiological nutrient concentrations, at odds with previous studies that indicated glutamine’s dominant role through reductive carboxylation under higher nutrient conditions. Further investigation into glutamine’s alternative roles in ccRCC cells suggested its major involvement in the bioenergetic TCA cycle, pyrimidine synthesis, and glutathione synthesis, which is also critical in ccRCC growth. The glutamine-dependent glutathione synthesis was also suggested as a possible metabolic vulnerability compared to normal kidney cells using a glutathione synthesis inhibitor. The current study provides a simple tool for studying an important aspect of lipid metabolism and suggests translational implications for targeting glucose-driven lipogenesis and glutamine-supported glutathione synthesis in ccRCC.
Strain-Enhanced Low-Temperature High Ionic Conductivity in Perovskite Nanopillar-Array Films
Chuanrui Huo - ,
Liyang Ma - ,
Yonghao Yao - ,
Xinyu Cui - ,
Shi Liu - ,
Shiqing Deng *- , and
Jun Chen *
Solid oxide ionic conductors with high ionic conductivity are highly desired for oxide-based electrochemical and energy devices, such as solid oxide fuel cells. However, achieving high ionic conductivity at low temperatures, particularly for practical out-of-plane transport applications, remains a challenge. In this study, leveraging the emergent interphase strain methodology, we achieve an exceptional low-temperature out-of-plane ionic conductivity in Na0.5Bi0.5TiO3 (NBT)-MgO nanopillar-array films. This ionic conductivity (0.003 S cm–1 at 400 °C) is over one order of magnitude higher than that of the pure NBT films and surpasses all conventional intermediate-temperature ionic conductors. Combining atomic-scale electron microscopy studies and first-principles calculations, we attribute this enhanced conductivity to the well-defined periodic alignment of NBT and MgO nanopillars, where the interphase tensile strain reaches as large as +2%. This strain expands the c-lattice and weakens the oxygen bonding, reducing oxygen vacancy formation and migration energy. Moreover, the interphase strain greatly enhances the stability of NBT up to 600 °C, well above the bulk transition temperature of 320 °C. On this basis, we clarify the oxygen migration path and establish an unambiguous strain–structure–ionic conductivity relationship. Our results demonstrate new possibilities for designing applicable high-performance ionic conductors through strain engineering.
Single-Molecule Resolved Conformational and Orbital Symmetry Breaking in Tetraphenylethylene-Based Macrocycles
En Li - ,
Tao Lin - ,
Songshan Dai - ,
Chengyi Chen - ,
Cheng-Kun Lyu - ,
Huilin Xie - ,
Jianyu Zhang - ,
Jacky Wing Yip Lam - ,
Ben Zhong Tang - ,
Jun Zhu - , and
Nian Lin *
Tetraphenylethylene (TPE) is a prototype aggregate-induced emission molecule. TPE-based conjugated macrocycles exhibit unique optical properties due to their peculiar cyclic topology. Because the symmetry of macrocycles strongly affects their photophysical properties, here we report a single-molecule study of the structures and orbitals of two TPE-based macrocycles of (C26H18)4 and (C26H18)6. Using scanning tunneling microscopy and spectroscopy, we discover that both macrocycles undergo spontaneous symmetry breaking in their conformations and frontier orbitals. The computational analyses reveal that the symmetry breaking is driven by a subtle interplay of higher extended conjugation between phenyl and node carbon atoms and conformation flexibility of the macrocycles. The observed symmetry breaking in TPE-based macrocycles is expected to strongly alter their photophysical properties.
In Situ Welding Ionic Conductive Breakpoints for Highly Reversible All-Solid-State Lithium–Sulfur Batteries
Zhonghao Hu - ,
Chuannan Geng - ,
Jiwei Shi - ,
Qiang Li - ,
Haotian Yang - ,
Mingyang Jiang - ,
Li Wang - ,
Quan-Hong Yang *- , and
Wei Lv *
Poly(ethylene oxide) (PEO)-based solid-state lithium–sulfur batteries (SSLSBs) have garnered considerable interest owing to their impressive energy density and high safety. However, the dissolved lithium polysulfide (LiPS) together with sluggish reaction kinetics disrupts the electrolyte network, bringing about ionic conductive breakpoints and severely limiting battery performance. To cure this, we propose an in situ welding strategy by introducing phosphorus pentasulfide (P2S5) as the welding filler into PEO-based solid cathodes. P2S5 can react with LiPS to form ion-conducting lithium polysulfidophosphate (LSPS), which suppresses the interaction with PEO and in situ weld breakpoints within the ionic conductive network. Of interest, LSPS also shows another function, that is, to catalyze sulfur redox reactions by decreasing the activation energy of sulfur reduction reaction from 0.87 to 0.75 eV, mitigating the shuttle effect. The in situ welding strategy helps the assembled SSLSB to feature exceptional cycling stability and a high energy density of up to 358 Wh·kg–1 due to the high sulfur utilization. Our findings pave an avenue for practical high-performance SSLSBs with a novel welding filler for in situ welding of ionic conductive network.
Conformational Chirality of Single-Crystal Covalent Organic Frameworks
Zhipeng Zhou - ,
Guohong Cai - ,
Zeyue Zhang - ,
Guobao Li - ,
Dongyang Lou - ,
Shangqing Qu - ,
Yuyao Li - ,
Meiying Huang - ,
Wei Liu - ,
Zhikun Zheng - , and
Junliang Sun *
The crystallization of organic polymers is often hindered by chiral units, hence resulting in chiral organic polymers typically existing as amorphous or partially crystalline phases such as natural rubber and cellulose. Similarly, as an emerging crystalline chiral polymer, chiral covalent organic frameworks (COFs) also inevitably face a delicate balance between chiral units and crystallization, limiting their production and applications in separation, catalysis, and optics. Here, we present a general strategy for producing a series of conformational chiral COFs with high crystallinity through breaking the meso conformation of achiral COFs. Conformational chirality of COF-300 was constructed by involving chiral amino-acid derivative templates during synthesis and was proven to have excellent thermodynamic (200 °C annealing in air) and dynamic stability (61% cell volume change). The stereochemistry of the conformational chiral crystals can be controllably tuned by chiral templates, resulting in wide-range circular dichroism signals from ultraviolet to infrared wavelengths and absorption dissymmetry factors (gabs) varying by up to 300%, with a maximum of gabs = 0.012. This strategy paves the way for stereochemistry modification, property enhancement, and exploration of new applications of crystalline chiral materials.
Ligand Effects on the Emission Characteristics of Molecular Eu(II) Luminescence Thermometers
Roberto M. Diaz-Rodriguez - ,
Diogo A. Gálico - ,
Daniel Chartrand - , and
Muralee Murugesu *
Discrete molecular organometallic europium(II) complexes are promising functional materials due to their ability to behave as highly sensitive band-shift luminescence thermometers. Furthering our understanding of the design principles salient to the emission behavior of such systems is important for developing them in this emerging application. To this end, a series of pseudo-C4v-symmetric organometallic europium(II) complexes bearing systematically varying ligand sets were synthesized and characterized to probe the influence of subtle structural modification on their optical properties. Opto-structural correlation analyses via variable-temperature single-crystal X-ray diffraction and photoluminescence spectroscopy reveal a remarkable variability in properties among structurally similar complexes and a convoluted dependence of the emission characteristics on the stereoelectronic properties of the ligands. A few factors of particular influence are nevertheless identified, including the distance between the europium(II) ion and the basal plane of the square-pyramidal coordination polyhedron, the presence of pendant electron density that might further interact with the excited-state 5d orbitals, and, qualitatively, the metal–ligand flexibility of the construct. These results help to elucidate principles that govern the luminescence properties of organometallic europium(II) complexes with an eye to enabling the rational design of high-performance luminescence thermometers of this genre.
November 28, 2024
Water-Soluble Fluorescent Sensors for Quantification of Trace Cisplatin in Body Fluids from Clinical Cancer Patients
Zifeng Cao - ,
Rong Yan - ,
Jiao Chen - ,
Mengyao She - ,
Shanshan Jia - ,
Wei Sun - ,
Ping Liu *- ,
Shengyong Zhang - , and
Jian-Li Li *
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ACS Editors' Choice® is a collection designed to feature scientific articles of broad public interest. Read the latest articles
Accurate quantification of cisplatin (cDDP) in body fluids (blood, urine, and ascites) is crucial in monitoring therapeutic processes, assessing drug metabolism, and optimizing treatment schedules for cancer patients. Nonetheless, due to the inherent fluorescence and complexity of the body fluid matrix, along with the low cDDP concentrations in these fluids during treatment, using fluorescent sensors for fluid detection remains a subject of ongoing research. Herein, a series of water-soluble cDDP-activatable fluorescent sensors was rationally constructed by introducing thioether groups to the xanthene skeleton based on the chalcogenophilicity of platinum. These sensors exhibit excellent sensitivity and certain anti-interference capabilities for sensing cDDP in living cells, rat tissues, and zebrafish. Especially, with a simplified sample pretreatment procedure, for the first time, Rh3 and Rh4 have enabled quantitative detection of cDDP levels in diversiform body fluids from clinical ovarian and bladder cancer patients. These results are highly consistent with those obtained by ICP-MS detection. This work paves the way for utilizing fluorescent sensors in clinical body fluid analysis, thus potentially revolutionizing the monitoring methods of cDDP in clinic settings.
Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera
Adam G. Bond - ,
Miquel Muñoz i Ordoño - ,
Celia M. Bisbach - ,
Conner Craigon - ,
Nikolai Makukhin - ,
Elizabeth A. Caine - ,
Manjula Nagala - ,
Marjeta Urh - ,
Georg E. Winter *- ,
Kristin M. Riching *- , and
Alessio Ciulli *
This publication is Open Access under the license indicated. Learn More
Proteolysis targeting chimera (PROTAC) degraders are typically bifunctional with one E3 ligase ligand connected to one target protein ligand via a linker. While augmented valency has been shown with trivalent PROTACs targeting two binding sites within a given target protein, or used to recruit two different targets, the possibility of recruiting two different E3 ligases within the same compound has not been demonstrated. Here we present dual-ligase recruitment as a strategy to enhance targeted protein degradation. We designed heterotrivalent PROTACs composed of CRBN, VHL and BET targeting ligands, separately tethered via a branched trifunctional linker. Structure–activity relationships of 12 analogues qualifies AB3067 as the most potent and fastest degrader of BET proteins, with minimal E3 ligase cross-degradation. Comparative kinetic analyses in wild-type and ligase single and double knockout cell lines revealed that protein ubiquitination and degradation induced by AB3067 was contributed to by both CRBN and VHL in an additive fashion. We further expand the scope of the dual-ligase approach by developing a heterotrivalent CRBN/VHL-based BromoTag degrader and a tetravalent PROTAC comprising of two BET ligand moieties. In summary, we provide proof-of-concept for dual-E3 ligase recruitment as a strategy to boost degradation fitness by recruiting two E3 ligases with a single degrader molecule. This approach could potentially delay the outset of resistance mechanisms involving loss of E3 ligase functionality.
Early Folding Dynamics of i-Motif DNA Revealed by pH-Jump Time-Resolved X-ray Solution Scattering
Arnold M. Chan - ,
Sasha B. Ebrahimi - ,
Devleena Samanta - ,
Denis Leshchev - ,
Adam K. Nijhawan - ,
Darren J. Hsu - ,
Madeline B. Ho - ,
Namrata Ramani - ,
Irina Kosheleva - ,
Robert Henning - ,
Chad A. Mirkin - ,
Kevin L. Kohlstedt *- , and
Lin X. Chen *
The i-motif is a pH-responsive cytosine-rich oligonucleotide sequence that forms, under acidic conditions, a quadruplex structure. This tunable structural switching has made the i-motif a useful platform for designing pH-responsive nanomaterials. Despite the widespread application of i-motif DNA constructs as biomolecular switches, the mechanism of i-motif folding on the atomic scale has yet to be established. We investigate the early folding structural dynamics of i-motif oligonucleotides with laser-pulse-induced pH-jump time-resolved X-ray solution scattering. Following the pH-jump, we observe that the initial random coil ensemble converts into a contracted intermediate state within 113 ns followed by further folding on the 10 ms time scale. We reveal the representative structures of these transient species, hitherto unknown, with molecular dynamics simulations and ensemble fitting. These results pave the way for understanding metastable conformations of i-motif folding and for benchmarking emerging theoretical models for simulating noncanonical nucleic acid structures.
Reversible Circularly Polarized Luminescence Inversion and Emission Color Switching in Photo-Modulated Supramolecular Polymer for Multi-Modal Information Encryption
Kuo Fu - ,
Da-Hui Qu *- , and
Guofeng Liu *
Constructing circularly polarized luminescence (CPL) materials that exhibit dynamic handedness inversion and emissive color modulation for multimodal information encryption presents both a significant challenge and a compelling opportunity. Here, we have developed a pyridinethiazole acrylonitrile-cholesterol derivative (Z-PTC) that exhibits wavelength-dependent photoisomerization and photocyclization, enabling dynamic handedness inversion and emissive color modulation in supramolecular assemblies with decent CPL activity. Coordination with Ag+ ions form the Z-PTC Ag supramolecular polymer (SP1), which assembles into nanotubes displaying enhanced positive yellow-green CPL. Irradiation at 454 nm transforms SP1 into nanospheres of a mixture supramolecular polymer (SP2) of Z/E-PTC Ag, displaying inverted supramolecular chirality and emitting negative orange-yellow CPL. Reheating SP2 to 343 K restores the original nanotube structure via excellent reversible photoisomerization. Exposure to 365 nm light also induces CPL inversion from positive to negative and triggers morphological changes from SP1 to SP2. Prolonged irradiation causes further transformation into irregular supramolecular aggregate, shifting the emission color to blue and eliminating CPL. These dynamic properties of the multicolor CPL system, including reversible handedness inversion, can also be realized in the semisolid state, exhibiting promising potential for multimodal information encryption applications with enhanced security and complexity.
Three-Dimensional Mesoporous Covalent Organic Framework for Photocatalytic Oxidative Dehydrogenation to Quinoline
Chou-Hung Hsueh - ,
Chang He - ,
Jiaqi Zhang - ,
Xin Tan - ,
Haojie Zhu - ,
Weng-Chon Max Cheong - ,
An-Zhen Li - ,
Xin Chen - ,
Haohong Duan - ,
Yingbo Zhao *- , and
Chen Chen *
Developing precious metal-free catalysts for organic reactions under mild conditions is urgent. Herein, we report a three-dimensional covalent organic framework (3D-COF) with high crystallinity and permanent pores, termed 3D-TABPA-COF, for the oxidation of tetrahydroquinoline to quinoline. The 3D-TABPA-COF assembled based on N4,N4-bis(4′-amino-[1,1′-biphenyl]-4-yl)-[1,1′-biphenyl]-4,4′-diamine (TABPA) is the catalytic active center for the conversion of tetrahydroquinoline. The triphenylamine in the structure is an effective photosensitizer, which not only enhances the light absorption capacity but also facilitates the rapid transfer of photogenerated electrons and ensures effective carrier separation. The obtained 3D-TABPA-COF has a high specific surface area (2745.06 m2 g–1) and mesopores of 3.57 nm. This is attributed to the fact that the bor topology is not easy to interpenetrate. It can oxidize tetrahydroquinoline to obtain quinoline efficiently under visible light irradiation. In addition, we also performed various photochemical characterizations combined with density functional theory calculations to elucidate the reaction mechanism from tetrahydroquinoline to quinoline. This work provides a feasible strategy for constructing 3D-COF to achieve efficient photocatalytic organic reactions.
Efficient Light-Driven Ion Pumping for Deep Desalination via the Vertical Gradient Protonation of Covalent Organic Framework Membranes
Weipeng Xian - ,
Xiaoyi Xu - ,
Yongxin Ge - ,
Zhiwei Xing - ,
Zhuozhi Lai - ,
Qing-Wei Meng - ,
Zhifeng Dai - ,
Sai Wang *- ,
Ruotian Chen - ,
Ning Huang - ,
Shengqian Ma - , and
Qi Sun *
Traditional desalination methods face criticism due to high energy requirements and inadequate trace ion removal, whereas natural light-driven ion pumps offer superior efficiency. Current synthetic systems are constrained by short exciton lifetimes, which limit their ability to generate sufficient electric fields for effective ion pumping. We introduce an innovative approach utilizing covalent-organic framework membranes that enhance light absorption and reduce charge recombination through vertical gradient protonation of imine linkages during acid-catalyzed liquid–liquid interfacial polymerization. This technique creates intralayer and interlayer heterojunctions, facilitating interlayer hybridization and establishing a robust built-in electric field under illumination. These improvements enable the membranes to achieve remarkable ion transport across extreme concentration gradients (2000:1), with a transport rate of approximately 3.2 × 1012 ions per second per square centimeter and reduce ion concentrations to parts per billion. This performance significantly surpasses that of conventional reverse osmosis systems, representing a major advancement in solar-powered desalination technology by substantially reducing energy consumption and secondary waste.
Mechanistic Investigation of the Pseudo-Halogen Effect in Enantioselective Aminocatalyzed [6 + 4] and [10 + 6] Cycloadditions: Enabling Unique Favorskii-Like Rearrangements
Casper Džabbarov Barløse - ,
René Slot Bitsch - ,
Jonas Faghtmann - ,
Cristina Domínguez Escobar - ,
Maria Edith Casacchia - ,
Anne Kristensen - , and
Karl Anker Jørgensen *
A mechanistic investigation into the novel combination of the pseudo-halogen effect with enantioselective aminocatalysis unravels the mechanistic intricacies of [6 + 4] and [10 + 6] higher-order cycloadditions and the succeeding new Favorskii-like rearrangements. By introducing the OTf-group into the tropone framework, it can serve both as an activator for the cycloaddition and as a proficient leaving group within the corresponding cycloadduct, thus enabling unprecedented ring-contracting Favorskii-like rearrangements. Integrating the -OTf group creates an electron-deficient 6π-component leveraging the pseudo-halogen effect by enhancing the polarization and introducing new strategic interaction points. This modification complements electron-rich 4π- and 10π-components from amino-activated 2,4-dienals or indene-carbaldehydes. A comprehensive DFT investigation supported by experimental results demonstrates that the [6 + 4] system proceeds through a rate-limiting stepwise exo-cycloaddition leading to a cycloadduct initially in a boat-conformation, subsequently transitioning to the more stable chair-conformation. The change in conformation ensures an SN1-like expulsion of the -OTf group, generating a stable carbocation bridgehead primed for a novel Favorskii-like seven-to-six ring-contracting rearrangement, resulting in the experimentally observed product. As proof-of-concept for the cycloaddition/Favorskii-like rearrangement, it is demonstrated that this approach can be extended to an unprecedented [10 + 6] cycloaddition. In contrast to the [6 + 4] system, the [10 + 6] system distinguishes itself with a concerted SN1-like/Favorskii-like six-to-five ring-contracting rearrangement, representing the rate-limiting step. This novel concept results in the experimental isolation of structurally complex products in high peri-, diastereo-, and enantioselectivity with moderate yield. These findings demonstrate the pseudo-halogen effect’s multifaceted role in promoting and enabling novel reactivity.
November 27, 2024
Chemically Driven Division of Protocells by Membrane Budding
Pablo Zambrano - ,
Xiaoyao Chen - ,
Christine M. E. Kriebisch - ,
Brigitte A. K. Kriebisch - ,
Oleksii Zozulia - , and
Job Boekhoven *
This publication is Open Access under the license indicated. Learn More
Division is crucial for replicating biological compartments and, by extension, a fundamental aspect of life. Current studies highlight the importance of simple vesicular structures in prebiotic conditions, yet the mechanisms behind their self-division remain poorly understood. Recent research suggests that environmental factors can induce phase transitions in fatty acid-based protocells, leading to vesicle fission. However, using chemical energy to induce vesicle division, similar to the extant of life, has been less explored. This study investigates a mechanism of vesicle division by membrane budding driven by chemical energy without complex molecular machinery. We demonstrate that, in response to chemical fuel, simple fatty acid-based vesicles can bud off smaller daughter vesicles. The division mechanism is finely controlled by adjusting fuel concentration, offering valuable insights into primitive cellular dynamics. We showcase the robustness of self-division across different fatty acids, retaining encapsulated materials during division and suggesting protocell-like behavior. These results underscore the potential for chemical energy to drive autonomous replication in protocell models, highlighting a plausible pathway for the emergence of life. Furthermore, this study contributes to the development of synthetic cells, enhancing our understanding of the minimal requirements for cellular life and providing a foundation for future research in synthetic biology and the origins of life.
Scalable Melt Polymerization Synthesis of Covalent Organic Framework Films for Room Temperature Low-Concentration SO2 Detection
Sa Wang - ,
Yu Fu - ,
Fengdong Wang - ,
Xiyuan Wang - ,
Yi Yang - ,
Mengjin Wang - ,
Jian Wang - ,
En Lin - ,
Heping Ma - ,
Yao Chen - ,
Peng Cheng - , and
Zhenjie Zhang *
The development of highly efficient sensors for low-concentration SO2 at room temperature is important for human health and fine chemistry, but it still faces critical challenges. Herein, a scalable olefin-linked covalent organic framework (COF) with an ultramicroporous structure and abundant binding sites is first developed as the SO2 sensing material. The COF can adsorb SO2 of 220 cm3/g at 1 bar and 40 cm3/g at 0.01 bar and 298 K, surpassing all reported COFs. The computational and kinetic adsorption studies deeply unveil the selective adsorption mechanism for low-concentration SO2. Furthermore, the multicomponent gas mixture breakthrough experiments confirm that the COF can specifically capture low-concentration (2000 ppm) SO2. We innovated a melt polymerization technology to fabricate COF films with adjustable substrates and film thicknesses. COF films are directly grown on the interdigital electrodes to prepare the SO2 sensor device, which possesses a low detection limit (86 ppb) and excellent selectivity for SO2 in the presence of 10 other potentially interfering gases. Compared to other reported SO2 sensors, its overall performance is among the top. Prominently, the sensor maintains a stable output signal for more than two months, and recovery can be easily achieved by simply purifying nitrogen at room temperature without heating. This study marks the first use of COFs for SO2 sensing, opening new possibilities for COFs in the detection of low-concentration toxic gases and manufacturing gas sensor devices.
High-Performance Chemigenetic Potassium Ion Indicator
Dazhou Cheng - ,
Zhenlin Ouyang - ,
Xiaoyu He - ,
Yusuke Nasu - ,
Yurong Wen - ,
Takuya Terai *- , and
Robert E. Campbell *
Potassium ion (K+) is the most abundant metal ion in cells and plays an indispensable role in practically all biological systems. Although there have been reports of both synthetic and genetically encoded fluorescent K+ indicators, there remains a need for an indicator that is genetically targetable, has high specificity for K+ versus Na+, and has a high fluorescent response in the red to far-red wavelength range. Here, we introduce a series of chemigenetic K+ indicators, designated as the HaloKbp1 series, based on the bacterial K+-binding protein (Kbp) inserted into HaloTag7 self-labeled with environmentally sensitive rhodamine derivatives. This series of high-performance indicators features high brightness in the red to far-red region, large intensiometric fluorescence changes, and a range of Kd values. We demonstrate that they are suitable for the detection of physiologically relevant K+ concentration changes such as those that result from the Ca2+-dependent activation of the BK potassium channel.
Catalytic Asymmetric Transfer Hydrogenation of β,γ-Unsaturated α-Diketones
Zhifei Zhao - ,
Wennan Dong - ,
Jinggong Liu - ,
Shuang Yang - ,
Andrej Emanuel Cotman - ,
Qi Zhang *- , and
Xinqiang Fang *
Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and has been widely applied in the industrial production of drug molecules. However, despite the great success in ATH of ketones, highly efficient, regio- and stereoselective ATH on enones remains underdeveloped. Moreover, optically pure acyloins and 1,2-diols are both extremely useful building blocks in organic synthesis, medicinal chemistry, and materials science, but concise asymmetric approaches allowing access to different types of acyloins and 1,2-diols have scarcely been discovered. We report in this paper the first highly efficient ATH of readily accessible β,γ-unsaturated α-diketones. The protocol affords four types of enantioenriched acyloins and four types of optically pure 1,2-diols in highly regio- and stereoselective fashion. The synthetic value of this work has been showcased by the divergent synthesis of four related natural products. Moreover, systematic mechanistic studies and density functional theory (DFT) calculations have illustrated the origin of the reactivity divergence, revealed the different roles of aromatic and aliphatic substituents in the substrates, and provided a range of unique mechanistic rationales that have not been disclosed in ATH-related studies.
Activationless Charge Transfer Drives Photocurrent Generation in Organic Photovoltaic Blends Independent of Energetic Offset
Yifan Dong - ,
Rui Zheng - ,
Deping Qian - ,
Tack Ho Lee - ,
Helen L. Bristow - ,
Pabitra Shakya Tuladhar - ,
Hyojung Cha *- , and
James R. Durrant *
This publication is Open Access under the license indicated. Learn More
Organic photovoltaics (OPVs) have recently shown substantial progress in enhancing device efficiency, driven in particular by advances in the design of nonfullerene acceptors and the reduction of the energy offset driving exciton separation at the donor/acceptor interface. Herein, we employ temperature-dependent transient absorption spectroscopy to investigate the activation energy for charge generation and recombination in a range of bulk heterojunction blends with nonfullerene acceptors. Remarkably, we find that in all cases charge generation is almost activationless, in the range of 11–21 meV, independent of energetic offset. Geminate recombination is also observed to be almost activationless, with only the kinetics of bimolecular charge recombination being strongly temperature-dependent, with an activation energy >400 meV. Our observation of essentially activationless charge generation, independent of energy offset, strongly indicates that charge generation in such blends does not follow Marcus theory but can rather be considered an adiabatic process associated with the motion of thermally unrelaxed carriers.
Quantitative Unraveling of Exsolved Heteroboundaries for High-Temperature Electrocatalysis
Xiaoxin Zhang - ,
Xiao Xiao - ,
Qiuyue Zhang - ,
Zhou Chen - ,
Chang Jiang - ,
Mingshu Chen - ,
Ning Yan - ,
Shidi Mo - ,
Meng Wu - ,
Jianhui Li - ,
Jijie Huang *- ,
Abdullah N. Alodhayb - ,
Xianzhu Fu - ,
Min Chen - ,
Xinchun Lv - , and
Yifei Sun *
The application of perovskite oxide for high-temperature electrocatalysis is hindered by its limited activity. Exsolution is a smart strategy that allows the enrichment of the perovskite’s surface with highly reactive phases, yielding heteroboundaries. However, the identification of the exact catalytic role of this complex architecture is still elusive. Here we presented a quantitative analysis of the CO2 electroreduction reactivity of a series of perovskite thin film platforms (La0.4Ca0.4Ti0.94Ni0.06O3, LCTN) boosted by exsolved heteropical nanoparticles (particularly for Ni and NiO). The cross-scale electrochemical characterizations, together with density functional theory (DFT) modelings, have shown clear evidence that the boundary length of the NP/perovskite interface is strictly correlated with the CO2RR activity. The intrinsic reaction rate per active site at the NiO/LCTN boundary demonstrates a highest turnover frequency (TOF) of 7.05 ± 0.75 × 104 s–1 at 800 °C, which is 2.5 times and 4 orders of magnitude better than that of Ni/LCTN and LCTN, respectively. The ab initio molecular dynamics (AIMD) proves that the CO2 absorption at the NiO/LCTN boundary leverages a bidentate carbonate modality with a reduced dissociation energy barrier. Moreover, a multifold enhancement in oxygen exchange rate was confirmed, which correlated to the facilitated oxygen ion hopping between adjacent TiO6 octahedrons. Further near-ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) during CO2 electrolysis on model electrolyzers reveals the crucial role of the NiO/LCTN boundary in stabilizing oxidized carbon intermediates, raising the onset potential threshold of adventitious carbon as well as preventing its build-up.
Two Different Clar’s Sextets: Clar’s Rule Does Not Necessarily Contradict the Global Pathway of Conjugated Macrocycles
Pradeep P. Desale - ,
Min-Sung Ko - ,
Tae-Ho Roh - ,
Jeong-Im Ham - , and
Dong-Gyu Cho *
Two contradictory theories, Clar’s sextet and resonance theory, explain the stability of conjugated macrocycles using localized and delocalized models, respectively. To reconcile these theories and gain better insights, PAH-containing porphyrinoids were chosen as a representative class of conjugated macrocycles. Two types of Clar’s sextets were identified and proposed for the first time based on their interaction with global conjugated pathways: (i) shared sextets that integrate with and perturb the global resonance pathway, and (ii) independent sextets that are separate from the pathway and potentially stabilize or do not perturb it. To test our hypothesis, we synthesized precise regioisomers with and without an independent sextet to exclude variables such as steric hindrance, different PAH characteristics, and other elements. This task is challenging due to the extensive synthetic efforts needed for regioisomeric PAH-containing porphyrinoids. We focused on 2,3-vinylnaphthiporphyrin, which features shared sextets, because its o-regioisomers are readily accessible. Two distinct regioisomers (1,2-vinylnaphthiporphyrins) with an independent sextet were synthesized along with unexpected nonaromatic N-fused porphyrinoids. Our analysis shows that 1,2-vinylnaphthiporphyrins with an independent sextet are more aromatic than 2,3-vinylnaphthiporphyrin (nonaromatic). This sextet analysis was also applied to other reported and yet-to-be-synthesized PAH-containing porphyrinoids, and these results are consistent with our current study.
High-Throughput Search for Photostrictive Materials Based on a Thermodynamic Descriptor
Zeyu Xiang - ,
Yubi Chen - ,
Yujie Quan - , and
Bolin Liao *
Photostriction is a phenomenon that can potentially improve the precision of light-driven actuation, the sensitivity of photodetection, and the efficiency of optical energy harvesting. However, known materials with significant photostriction are limited, and effective guidelines to discover new photostrictive materials are lacking. In this study, we perform a high-throughput computational search for new photostrictive materials based on simple thermodynamic descriptors, namely, the band gap pressure and stress coefficients. Using the Δ-SCF method based on density functional theory, we establish that these descriptors can accurately predict intrinsic photostriction in a wide range of materials. Subsequently, we screened over 4770 stable semiconductors with a band gap below 2 eV from the Materials Project database to search for strongly photostrictive materials. This search identifies Te2I as the most promising candidate, with photostriction along out-of-plane direction exceeding 8 × 10–5 with a moderate photocarrier concentration of 1018 cm–3. Furthermore, we provide a detailed analysis of factors contributing to strong photostriction, including bulk moduli and band-edge orbital interactions. Our results provide physical insights into the photostriction of materials and demonstrate the effectiveness of using simple descriptors in high-throughput searches for new functional materials.
Real-Space Spectral Determination of Short Single-Stranded DNA Sequence Structures
Yu Han - ,
Li Dong - ,
Lu-Yao Zhu - ,
Chun-Rui Hu - ,
Hang Li - ,
Yang Zhang - ,
Chao Zhang *- ,
Yao Zhang *- , and
Zhen-Chao Dong *
Resolving the sequence and structure of flexible biomolecules such as DNA is crucial to understanding their biological mechanisms and functions. Traditional structural biology methods remain challenging for the analysis of small and disordered biomolecules, especially those that are difficult to label or crystallize. Recent development of single-molecule tip-enhanced Raman spectroscopy (TERS) offers a label-free approach to identifying nucleobases in a single DNA chain. However, a clear demonstration of sequencing both spatially and spectrally at single-base resolution is still elusive due to the challenges caused by weak Raman signals and the flexibility of DNA molecules. Here, we report a proof-of-principle demonstration to this end, spectrally resolving in real space individual nucleobases and their sequence structures within a short, single-stranded DNA molecule artificially designed. This breakthrough is achieved through the development of subnanometer-resolved low-temperature TERS methodology for such thermally unstable flexible biomolecules. Further TERS mapping over individual nucleobases provides additional structural information about the molecular configurations and even the locations of functional groups, offering a way to track modification types and binding sites in biomolecules.
Enantioselective Alkylation of Primary C(sp3)–H Bonds in N-Methyl Tertiary Amine Enabled by Iridium Complex of Axially Chiral β-Aryl Porphyrins
Shanshan Yuan - ,
Sheng-Yu Li - ,
Xiao-Ming Zhao *- ,
Ya-Zhou Lin - , and
Sheng-Cai Zheng *
A fine-tuning of enantioselective carbene insertion into primary C(sp3)–H bonds has been realized in challenging substrates, such as N-methyl unblocked aromatic and non-deactivated aliphatic tertiary amines, in which sterically demanding β-axially chiral iridium porphyrin catalysts play a crucial role. This primary C(sp3)–H alkylation with diazo compounds affords a series of β-chiral tertiary amines in high yields with excellent enantioselectivities. Notably, the protocol was successfully applied to the postmodification of chiral bicuculline, yielding the desired derivative with high diastereoselectivity. This approach paves a facile way for the stereodivergent derivation of chiral alkaloid natural products featuring an N-methyl handle. In addition, a mechanism for the reaction was proposed based on deuterium experiments and an identified cationic iridium species via HRMS analysis.
Cryo-EM Structures Reveal the Unique Binding Modes of Metyltetraprole in Yeast and Porcine Cytochrome bc1 Complex Enabling Rational Design of Inhibitors
Yu-Xia Wang - ,
Ying Ye - ,
Zhi-Wen Li - ,
Guang-Rui Cui - ,
Xing-Xing Shi - ,
Ying Dong - ,
Jia-Jia Jiang - ,
Jia-Yue Sun - ,
Ze-Wei Guan - ,
Nan Zhang - ,
Qiong-You Wu - ,
Fan Wang - ,
Xiao-Lei Zhu *- , and
Guang-Fu Yang *
Cytochrome bc1 (complex III) represents a significant target for the discovery of both drugs and fungicides. Metyltetraprole (MET) is commonly classified as a quinone site inhibitor (QoI) that combats the G143A mutated isolate, which confers high resistance to strobilurin fungicides such as pyraclostrobin (PYR). The binding mode and antiresistance mechanism of MET remain unclear. Here, we determined the high-resolution structures of inhibitor-bound S. cerevisiae complex III (MET, 2.52 Å; PYR, 2.42 Å) and inhibitor-bound porcine complex III (MET, 2.53 Å; PYR, 2,37 Å) by cryo-electron microscopy. The distinct binding modes of MET and PYR were observed for the first time. Notably, the MET exhibited different binding modes in the two species. In S. cerevisiae, the binding site of MET was the same as PYR, serving as a Pm-type inhibitor of the Qo site. However, in porcine, MET acted as a dual-target inhibitor of both Qo and Qi. Based on the structural insights, a novel inhibitor (YF23694) was discovered and demonstrated excellent fungicidal activity against downy mildew and powdery mildew fungi. This work provides a new starting point for the design of the next generation of inhibitors to overcome the resistance.
Slow Dephasing of Coherent Optical Phonons in Two-Dimensional Lead Organic Chalcogenides
Hanjun Yang *- ,
Sagarmoy Mandal - ,
Bowen Li - ,
Tushar Kanti Ghosh - ,
Jonas Mark Peterson - ,
Peijun Guo - ,
Letian Dou - ,
Ming Chen *- , and
Libai Huang *
Hybrid organic–inorganic semiconductors with strong electron–phonon interactions provide a programmable platform for developing a variety of electronic, optoelectronic, and quantum materials by controlling these interactions. However, in current hybrid semiconductors such as halide perovskites, anharmonic vibrations with rapid dephasing hinder the ability to coherently manipulate phonons. Here, we report the observation of long-lived coherent phonons in lead organic chalcogenides (LOCs), a new family of hybrid two-dimensional semiconductors. These materials feature harmonic phonon dynamics despite distorted lattices, combining long phonon dephasing times with tunable semiconducting properties. A dephasing time -up to 75 ps at 10 K, with up to ∼500 cycles of phonon oscillation between scattering events, was observed, corresponding to a dimensionless harmonicity parameter that is more than an order of magnitude larger than that of halide perovskites. The phonon dephasing time is significantly influenced by anharmonicity and centrosymmetry, both of which can be tuned through the design of the organic ligands enabled by the direct bonding between the organic and inorganic motifs. This research opens new opportunities for the manipulation of electronic properties with coherent phonons in hybrid semiconductors.
Bottlebrush Polymers with Sequence-Controlled Backbones for Enhanced Oligonucleotide Delivery
Yun Wei - ,
Peiru Chen - ,
Mengqi Ren - ,
Deng Li - ,
Jiachen Lin - ,
Tingyu Sun - ,
Yuyan Wang - ,
Shaobo Yang - ,
Christopher Nenopoulos - ,
Christopher Oetheimer - ,
Yao Li - ,
Chenyang Xue - ,
Mona Minkara - , and
Ke Zhang *
This publication is Open Access under the license indicated. Learn More
The clinical translation of oligonucleotide-based therapeutics continues to encounter challenges in delivery. In this study, we introduce a novel class of delivery vehicles for oligonucleotides that are based on poly(ethylene glycol) (PEG) bottlebrush polymers with sequence-defined backbones. Using solid-phase synthesis and bespoke phosphoramidites, the oligonucleotide and the polymer backbone can be assembled on the solid support. The synthesis allows chemical modifiers such as carbon 18 (C18) units to be incorporated into the backbone in specific patterns to modulate the cell–material interactions. Subsequently, PEG side chains were grafted onto the polymer segment of the resulting polymer–oligonucleotide conjugate, yielding bottlebrush polymers. We report an optimal pattern of the C18 modifier that leads to improved cellular uptake, plasma pharmacokinetics, biodistribution, and antisense activity in vivo. Our results provide valuable insights into the structure–property relationship of polymer–oligonucleotide conjugates and suggest the possibility of tuning the polymer backbone to meet the specific delivery requirements of various diseases.
Activation of Strong π–Acids at [Fe4S4]+ Clusters Enabled by a Noncanonical Electronic Structure
Alexandra C. Brown - ,
Niklas B. Thompson - , and
Daniel L. M. Suess *
Although Fe–S clusters are privileged metallocofactors for the reduction of N2, CO, and other π-acidic substrates, their constituent metal ions─high-spin Fe2+ and Fe3+─are typically not amenable to binding and activating strong π-acids. Here, we demonstrate that [Fe4S4]+ clusters can overcome this limitation by adopting a noncanonical electronic structure. Specifically, we report the synthesis and characterization of a series of 3:1 site-differentiated [Fe4S4]+ clusters in which the unique Fe site is bound by one of 10 electronically variable arylisocyanide ligands. Rather than being continuously tuned as a function of the arylisocyanides’ electronic properties (e.g., as quantified by linear free energy relationships), the structures of the clusters are divided into two groups: (i) those with moderately π-acidic isocyanides, which adopt a “typical” structure characterized by standard bond metrics and geometric distortions from tetrahedral symmetry, and (ii) those with more strongly π-acidic isocyanides, which adopt a “contracted” structure with an unusually symmetric geometry and a compressed cluster core. Computational studies revealed that although the “typical” structure has a canonical electronic structure, the “contracted” structure has a noncanonical arrangement of spin density, with a full complement of π-backbonding electrons and more substantial Fe–Fe delocalization. These features of the “contracted” structure enable substantial C≡N bond weakening of the strongest π-acceptors in the series. More generally, the experimental characterization of the “contracted” electronic isomer suggests that other noncanonical electronic structures of Fe–S clusters remain to be discovered.
Charting Regions of Cobalt’s Chemical Space with Maximally Large Magnetic Anisotropy: A Computational High-Throughput Study
Lorenzo A. Mariano - ,
Vu Ha Anh Nguyen - ,
Valerio Briganti - , and
Alessandro Lunghi *
This publication is Open Access under the license indicated. Learn More
Magnetic anisotropy slows down magnetic relaxation and plays a prominent role in the design of permanent magnets. Coordination compounds of Co(II) in particular exhibit large magnetic anisotropy in the presence of low-coordination environments and have been used as single-molecule magnet prototypes. However, only a limited sampling of cobalt’s vast chemical space has been performed, potentially obscuring alternative chemical routes toward large magnetic anisotropy. Here we perform a computational high-throughput exploration of Co(II)’s chemical space in search of new single-molecule magnets. We automatically assemble a diverse set of ∼15,000 novel complexes of Co(II) and fully characterize them with multireference ab initio methods. More than 100 compounds exhibit magnetic anisotropy comparable to or larger than leading known compounds. The analysis of these results shows that compounds with record-breaking magnetic anisotropy can also be achieved with coordination four or higher, going beyond the established paradigm of two-coordinated linear complexes.
Impact of Transition-State Aromaticity on Selective Radical–Radical Coupling of Triarylimidazolyl Radicals
Kazunori Okamoto - ,
Sayaka Hatano - , and
Manabu Abe *
This publication is Open Access under the license indicated. Learn More
Radical coupling reactions are generally known to have a low selectivity due to the high reactivity of radicals. In this study, high regio and substrate selectivity was discovered in the dimerization of triarylimidazolyl radicals (TAIR), a versatile photochromic reaction. When two different radicals, 2-(4-cyanophenyl)-4,5-diphenyl-1H-imidazolyl radical (CN-TAIR) and 2-(4-methoxyphenyl)-4,5-diphenyl-1H-imidazolyl radical (OMe-TAIR), were simultaneously generated in situ, a hexaarylbiimidazole, formed by selective coupling at the nitrogen atom at position 1 of CN-TAIR and the carbon atom at position 2 of OMe-TAIR, was isolated with high selectivity as the main product among 24 possible radical dimer hexaarylbiimidazole derivatives. This high regio and substrate selectivity cannot be explained solely by the stability of the product and/or the electrophilicity and nucleophilicity of the radicals but originates from the aromaticity of the transition state in the radical–radical coupling reaction. To date, the selectivity of radical coupling reactions has been thought to be controlled by steric hindrance and radical spin density, but this study revealed a new factor for controlling radical coupling, that is, transition-state aromaticity. Aromaticity has been reported to have an important effect not only in the reactivity and structure of ground-state molecules but also on the electronically excited states and transition states in pericyclic reactions such as the Diels–Alder reaction and the Cope–Claisen rearrangement. This study demonstrated for the first time that radical coupling reactions can also be controlled by transition-state aromaticity.
Engineering Supramolecular [c2]Daisy Chains for Structural Hierarchy-Dependent Emission and Photoreactivity
Jiahui Xu - ,
Shengyong Deng - , and
Peifa Wei *
Organic photofunctional materials exhibit properties that are highly dependent on their structural hierarchy. The variability in intermolecular interactions and molecular packing in both monomeric and aggregated states complicates the controllability and predictability of their photophysical and photochemical properties. To address this challenge, we developed three luminescent supramolecular [c2]daisy chains as simplified models. The rigid and mutually embedded linkers between the host and guests facilitate the formation of [c2]daisy chains with balanced stability and dynamics. Additionally, the close and tunable π–π interactions between the luminescent units provide a structural basis for fluorescence modulation and topochemical photoreactions. We performed two sets of comparisons to assess luminescence and photoreactivity: one comparison involves molecules with and without crown ethers, and the other contrasting their behavior under UV excitation in solution (diluted and concentrated) versus in the aggregated and crystalline states. Specifically, in the crystalline state, [c2]daisy chains effectively stabilize molecular packing, leading to highly efficient dimer-dependent emission. This unique structure remains in both solution (c > 1 mM) and aggregated states, which can direct the reaction pathway toward rapid and efficient intermolecular photocycloaddition upon UV irradiation. However, in highly diluted solution (10 μM), [c2]daisy chains dissociate into monomers, which further undergo intramolecular photocyclization. This study provides new insights into employing supramolecular strategies for controllable molecular aggregation and the fine-tuning of photoreaction pathways and kinetics.
November 26, 2024
Simultaneous Formation of a Foldamer and a Self-Replicator by Out-of-Equilibrium Dynamic Covalent Chemistry
Ankush Sood - ,
Pradeep K. Mandal - ,
Jim Ottelé - ,
Juntian Wu - ,
Marcel Eleveld - ,
Joydev Hatai - ,
Charalampos G. Pappas - ,
Ivan Huc *- , and
Sijbren Otto *
This publication is Open Access under the license indicated. Learn More
Systems chemistry has emerged as a useful paradigm to access structures and phenomena typically exhibited by living systems, including complex molecular systems such as self-replicators and foldamers. As we progress further toward the noncovalent synthesis of life-like systems, and eventually life itself, it is necessary to gain control over assembly pathways. Dissipative chemical fueling has enabled access to stable populations of (self-assembled) structures that would normally form only transiently. Here, we report a synthetic dynamic combinatorial library, made from a single structurally simple building block, from which a self-replicator and a foldamer can emerge along two distinct and competing pathways through an inter- or intramolecular assembly process, respectively. A fueled chemical reaction cycle is then set up to generate the foldamer transiently, in the presence of the self-replicator. The partitioning of the building block between the folding and self-replication pathways and the duration of the fueled reaction cycles are controlled by adjusting the amount of the chemical fuel. An out-of-equilibrium steady state involving the two assemblies could also be achieved by using a continuous stirred tank reactor with inflow and outflow of material. This work connects the domains of folding and self-replication in synthetic systems through dissipative out-of-equilibrium chemistry. It demonstrates that foldamers and self-replicators, formed from the same building block, can stably coexist if the system is continuously supplied with energy, while at equilibrium, the Gibbs phase rule prohibits such coexistence.
Light-Mediated Interconversion between a Foldamer and a Self-Replicator
Yulong Jin *- ,
Pradeep K. Mandal - ,
Juntian Wu - ,
Armin Kiani - ,
Rui Zhao - ,
Ivan Huc *- , and
Sijbren Otto *
This publication is Open Access under the license indicated. Learn More
Self-replicating molecules and well-defined folded macromolecules are of great significance in the emergence and evolution of life. How they may interconnect and affect each other remains largely elusive. Here, we demonstrate an abiotic system where a single building block can oligomerize to yield either a self-replicating molecule or a foldamer. Specifically, agitation of a disulfide-based dynamic combinatorial library at moderately elevated pH channels it selectively into a self-replicating hexamer assembled into fibers, after passing through a period where a 15-subunit macrocyclic foldamer existed transiently. Without mechanoagitation or at lower pH, the formation of hexamer fiber is suppressed, resulting in the accumulation of the 15mer foldamer. Foldamer and self-replicator can be interconverted in response to external stimuli, including agitation and a change in pH. Furthermore, upon the addition of a photoacid, the pH of the medium can be controlled by irradiation, driving the switching between replicator and foldamer and allowing a dissipative out-of-equilibrium state to be accessed, using light as a source of energy.
Copper-Mediated Cross-Coupling Selective for Pyroglutamate Post-Translational Modifications
Yuxuan Ding - ,
Yuecheng Jiang - ,
Nicolas Lorenzo Serrat - ,
Kangbao Zhong *- ,
Yu Lan *- , and
Zachary T. Ball *
Pyroglutamate is a cyclic N-terminal post-translational modification that occurs in both proteins and peptide hormones. The prevalence and biological roles of pyroglutamate are little understood, in part due to limited tools to identify, quantify, and manipulate its pyrrolidinone structure. Selective modification of pyroglutamate residues in complex polypeptides may provide unique tools to better understand its biological roles and to allow late-stage diversification of biologically active pyroglutamate-containing sequences. This work describes a copper-catalyzed N–H cross-coupling of unprotected peptides that is selective for N-terminal pyroglutamate residues. The reaction is operationally simple under mild conditions and tolerates all canonical residues. Mechanistic studies point to a key role for a multidentate copper-binding mode of the extended polypeptide structure in delivering the observed reactivity. The reaction allows for direct labeling and identification of a pyroglutamate hormone present in porcine intestinal extracts.
A Discrete Trialane with a Near-Linear Al3 Axis
Debabrata Dhara - ,
Lukas Endres - ,
Aritra Roy - ,
Rian D. Dewhurst - ,
Rüdiger Bertermann - ,
Felipe Fantuzzi *- , and
Holger Braunschweig *
This publication is Open Access under the license indicated. Learn More
The presence of inherent electronic unsaturation in aluminum predominantly results in the formation of aluminum clusters, with very few examples of compounds containing discrete chains of aluminum atoms in existence. In this work, we present the successful synthesis and structural authentication of a highly unusual trialane species with a near-linear chain of three Al atoms, alongside a carbene-stabilized aluminyl anion ([LAlR2]−), an alternative product produced by varying the reaction conditions. Quantum-chemical calculations have been applied to elucidate the electronic structure and bonding of these novel compounds. Additionally, we successfully trapped a reaction intermediate using an alkyne, suggesting the intermediacy of a base-stabilized monomeric alumylene (LRAl:), which is also investigated through computational methods.
Processable Coordination Polymer Inks for Highly Conductive and Robust Coatings
Patrick M. Crossland - ,
Chen-Yu Lien - ,
Liam O. de Jong - ,
Joseph L. Spellberg - ,
Maia E. Czaikowski - ,
Lei Wang - ,
Alexander S. Filatov - ,
Sarah B. King - , and
John S. Anderson *
The unique properties and processability of conducting and semiconducting organic materials have fascinated scientists since their discovery. Of this broad class of materials, conductive coordination polymers are of immense recent interest due to their innate modularity and tunability. However, these materials are typically generated as powders and, in some cases, single crystals which significantly limits possible processing and many applications. Herein, we report a method that enables solution-phase processing of a previously reported highly conductive coordination polymer, NiTTFtt (TTFtt = tetrathiafulvalenetetrathiolate), into thin films and conductive textiles. Thin films of NiTTFtt show record-breaking conductivity for a coordination polymer and unusual physical behavior that sheds light on the transport mechanisms in this glassy metallic material. Textiles coated with NiTTFtt are conductive and durable to air, water, washing, acid, base, and mechanical cycles. The properties and processability of NiTTFtt reported here make it notable among coordination polymers and conducting organic materials more broadly.
Isocyanide Ligation Enables Electrochemical Ammonia Formation in a Synthetic Cycle for N2 Fixation
Jeremy E. Weber - ,
Noah D. McMillion - ,
Alexander S. Hegg - ,
Ashlee E. Wertz - ,
Mehrnaz Aliahmadi - ,
Brandon Q. Mercado - ,
Robert H. Crabtree - ,
Hannah S. Shafaat *- ,
Alexander J. M. Miller *- , and
Patrick L. Holland *
Transition-metal-mediated splitting of N2 to form metal nitride complexes could constitute a key step in electrocatalytic nitrogen fixation, if these nitrides can be electrochemically reduced to ammonia under mild conditions. The envisioned nitrogen fixation cycle involves several steps: N2 binding to form a dinuclear end-on bridging complex with appropriate electronic structure to cleave the N2 bridge followed by proton/electron transfer to release ammonia and bind another molecule of N2. The nitride reduction and N2 splitting steps in this cycle have differing electronic demands that a catalyst must satisfy. Rhenium systems have had limited success in meeting these demands, and studying them offers an opportunity to learn strategies for modulating reactivity. Here, we report a rhenium system in which the pincer supporting ligand is supplemented by an isocyanide ligand that can accept electron density, facilitating reduction and enabling the protonation/reduction of the nitride to ammonia under mild electrochemical conditions. The incorporation of isocyanide raises the N–H bond dissociation free energy of the first N–H bond by 10 kcal/mol, breaking the usual compensation between pKa and redox potential; this is attributed to the separation of the protonation site (nitride) and the reduction site (delocalized between Re and isocyanide). Ammonia evolution is accompanied by formation of a terminal N2 complex, which can be oxidized to yield bridging N2 complexes including a rare mixed-valent complex. These rhenium species define the steps in a synthetic cycle that converts N2 to NH3 through an electrochemical N2 splitting pathway, and show the utility of a second, tunable supporting ligand for enhancing nitride reactivity.
Interaction-Dependent Secondary Structure of Peptides in Biomolecular Condensates
Keegan A. Lorenz-Ochoa - ,
Moonyeon Cho - ,
Sapun H. Parekh - , and
Carlos R. Baiz *
Biomolecular condensates provide a mechanism for compartmentalization of biomolecules in eukaryotic cells. These liquid-like condensates are formed via liquid–liquid phase separation, by a plethora of interactions, and can mediate several biological processes in healthy cells. Expansions of dipeptide repeat proteins, DPRs, in which arginine rich DPRs like poly-proline-arginine (PR), and poly-glycine-arginine (GR), partition RNA into condensates can however induce cell toxicity. Here, we use (GR)20 as a model for biological poly-GR and condense it using either excluded volume interactions with polyethylene glycol (PEG) as a crowder or direct electrostatic interactions with RNA oligomers. Using two-dimensional infrared (2D IR) spectroscopy, we observe that (GR)20 condensed through an excluded volume forms β-sheet structures, whereas (GR)20 condensed with RNA forms loops. We also investigate local hydrogen-bond dynamics in the condensate and compare the measurements with molecular dynamics simulations. Hydrogen bond lifetimes undergo a marked slowdown compared to dynamics in the dilute phase. This is representative of confined water within the percolated networks inside the condensate due to the interaction present in the condensate disrupting H-bond networks. Overall, our results show that both protein structure and dynamics are inherently dependent on the type of interactions that stabilize the condensates.
Synthesis of P(V)-Stereogenic Phosphorus Compounds via Organocatalytic Asymmetric Condensation
Fengrui Che - ,
Junyuan Hu - ,
Minghong Liao - ,
Zhongfu Luo - ,
Hongyan Long - ,
Benpeng Li - ,
Yonggui Robin Chi - , and
Xingxing Wu *
Enantioenriched phosphorus(V)-stereogenic compounds, featuring a pentavalent phosphorus atom as the stereogenic center, are crucial in various natural products, drugs, bioactive molecules, and catalysts/ligands. While a handful of stereoselective synthetic approaches have been developed, achieving direct stereocontrol at the phosphorus atom through catalytic generation of phosphorus(V)-heteroatom bonds continues to be a formidable challenge. Here, we disclose an organocatalytic asymmetric condensation strategy that employs a novel activation mode of stable feedstock phosphinic acids by the formation of mixed phosphinic anhydride as the reactive species to facilitate further catalyst-controlled asymmetric P–O bond formations, involving a dynamic kinetic asymmetric transformation (DYKAT) process with alcohol nucleophiles via a cinchonidine-derived bifunctional catalyst. The resulting H-phosphinate intermediates allow further stereospecific derivatizations, affording modular access to a diverse library of chiral phosphonates and phosphonamidates with notable antibacterial activity. Furthermore, this synthetic platform facilitates P–O/N coupling with various natural products and drugs, presenting a valuable tool for medicine and agrochemical discovery.
Why Does a Transition Metal Dichalcogenide Nanoribbon Narrow into a Nanowire under Electron Irradiation?
Yue Liu - ,
Tian Cui *- , and
Da Li *
Transition metal dichalcogenide (TMDC) nanowires have practical applications in 1D electron channels, spintronics, optoelectronics, and catalysis due to their authentic subnanometer width (<1 nm) and intrinsic metallicity. Although narrowing of a TMDC nanoribbon into a nanowire under electron irradiation has been frequently observed in the synthesis of TMDC nanowires, the mechanism underlying this unexpected structural transformation remains a mystery. Here, to reveal the underlying mechanism, we combine first-principles calculations with a global structure search of 1D nanowires and show that a nanoribbon of 1H-phase MoS2 with a width narrower than 6 rings is energetically unfavorable compared with its nanowire counterpart due to the edge–edge interaction. The bending effect induced by S defects under electron irradiation is the major driving force for the transition of MoS2 nanoribbon into a nanowire. We predict that the precursor of the Mo6S6 nanowire is a well-defined Mo11S11-i nanowire with an unexpected stoichiometry. The intrinsic local compressive strain triggers a phase transition from Mo11S11-i to its slightly modified sister nanowire, Mo11S11-ii, which is characterized by the configuration (Mo1S1)5&Mo6S6. Triggered by electron irradiation, the nanoribbon undergoes a step-by-step narrowing process with sequential peeling of a Mo1S1 fragment in each step to form a robust Mo6S6 nanowire. This unique narrowing mechanism is universal for the nanoribbon-to-nanowire transformation of other TMDCs under electron irradiation. Our study highlights a hitherto unexplored mechanism for creating individual M6X6 nanowires and contributes to an in-depth understanding of the narrowing of TMDC nanoribbons under electron irradiation.
Deriving Chiroptical Properties from Intrinsically Achiral Building Blocks of One-Dimensional CsPbBr3 Perovskite Nanowires
Shramana Guha - ,
Suman Bera - ,
Arghyadeep Garai - ,
D. D. Sarma - ,
Narayan Pradhan - , and
Somobrata Acharya *
Chirality is a ubiquitous feature in biological systems and occurs even in certain inorganic crystals. Interestingly, some inorganic nanocrystals have been shown to possess chirality, despite their achiral bulk forms. However, the mechanism of chirality formation and chiroptical responses in such nanocrystals is still ambiguous due to the presence of chiral organic ligands used to passivate such nanocrystals. Here, we recognize intrinsic chiroptical responses from lead halide perovskite nanowires with different length scales. Cube-connected nanowires with minimum interfacial contacts make their arrangement chiral for chiroptical responses even in the absence of chiral ligands. The chiral nanowires with varying lengths serve as a systematic platform for improving dissymmetric factors significantly with increasing lengths. The dissymmetric factor of the longest nanowires reaches 1.4 × 10–2, which is the highest among the intrinsic chiral perovskite nanocrystals at present. The nanowires generate circularly polarized luminescence, which has been seldom reported in halide perovskite nanocrystals in the absence of any chiral ligands. Furthermore, we find that chirality exists in the basic unit consisting of two corner-connected cubes in the form of a dimer. The intrinsic chirality of the nanowires is determined by the lattice rotation of connected cubes along the interfacial boundaries, which is different from the commonly observed chirality induced by chiral ligands. Such chiral lead halide perovskite nanocrystals with robust chiroptical properties provide an ideal platform for understanding the origin of intrinsic chirality and the rational design of anisotropic chiral nanostructures.
Catalytic Enantioselective Hydrogen Atom Abstraction Enables the Asymmetric Oxidation of Meso Diols
Nelson Y. S. Lam - ,
Jyoti Dhankhar - ,
Antti S. K. Lahdenperä - , and
Robert J. Phipps *
This publication is Open Access under the license indicated. Learn More
Desymmetrization of meso diols is an important strategy for the synthesis of chiral oxygen-containing building blocks. Oxidative desymmetrization is an important subclass, but existing methods are often constrained by the need for activated alcohol substrates. We disclose a conceptually distinct strategy toward oxidative diol desymmetrization that is enabled by catalytic enantioselective hydrogen atom abstraction. Following single electron oxidation of a cinchona alkaloid-derived catalyst, enantiodetermining hydrogen atom abstraction generates a desymmetrized ketyl radical intermediate which reacts with either DIAD or O2 before in situ elimination to form valuable hydroxyketone products. A range of cyclic and acyclic meso diols are competent, defining the absolute configuration of up to four stereocenters in a single operation. As well as providing rapid access to complex hydroxyketones, this work emphasizes the broad synthetic potential of harnessing hydrogen atom abstraction in an enantioselective manner.
November 25, 2024
An Activity-Based Sensing Approach to Multiplex Mapping of Labile Copper Pools by Stimulated Raman Scattering
Yishu Jiang - ,
Elsy El Khoury - ,
Aidan T. Pezacki - ,
Naixin Qian - ,
Miku Oi - ,
Laura Torrente - ,
Sophia G. Miller - ,
Martina Ralle - ,
Gina M. DeNicola - ,
Wei Min *- , and
Christopher J. Chang *
Molecular imaging with analyte-responsive probes offers a powerful chemical approach to studying biological processes. Many reagents for bioimaging employ a fluorescence readout, but the relatively broad emission bands of this modality and the need to alter the chemical structure of the fluorophore for different signal colors can potentially limit multiplex imaging. Here, we report a generalizable approach to multiplex analyte imaging by leveraging the comparably narrow spectral signatures of stimulated Raman scattering (SRS) in activity-based sensing (ABS) mode. We illustrate this concept with two copper Raman probes (CRPs), CRP2181 and CRP2153.2, that react selectively with loosely bound Cu(I/II) and Cu(II) ions, respectively, termed the labile copper pool, through copper-directed acyl imidazole (CDAI) chemistry. These reagents label proximal proteins in a copper-dependent manner using a dye scaffold bearing a 13C≡N or 13C≡15N isotopic SRS tag with nearly identical physiochemical properties in terms of shape and size. SRS imaging with the CRP reagents enables duplex monitoring of changes in intracellular labile Cu(I) and Cu(II) pools upon exogenous copper supplementation or copper depletion or genetic perturbations to copper transport proteins. Moreover, CRP imaging reveals reciprocal increases in labile Cu(II) pools upon decreases in activity of the antioxidant response nuclear factor-erythroid 2-related factor 2 (NRF2) in cellular models of lung adenocarcinoma. By showcasing the use of narrow-bandwidth ABS probes for multiplex imaging of copper pools in different oxidation states and identifying alterations in labile metal nutrient pools in cancer, this work establishes a foundation for broader SRS applications in analyte-responsive imaging in biological systems.
Correlating Halide Segregation with Photolysis in Mixed-Halide Perovskites via In situ Opto-gravimetric Analysis
Zhaojian Xu - ,
Xinjue Zhong - ,
Tuo Hu - ,
Junnan Hu - ,
Antoine Kahn - , and
Barry P. Rand *
Halide oxidation plays a fundamental role in halide segregation and the degradation of halide perovskites, yet quantitative measurement of halide oxidation in solid-state perovskite samples remains challenging. Herein, we demonstrate that in situ opto-gravimetric measurements based on a quartz crystal microbalance can quantify the photolysis kinetics of solid-state perovskites. By investigating a series of mixed bromide/iodide perovskites with varying halide ratios, we demonstrate identical compositional thresholds (x ∼ 0.4 in the CsPb(BrxI1–x)3 system) for iodide oxidation, light-induced halide segregation, and photolysis. Our findings reveal the correlation between these light-induced instabilities and unambiguously explain the photolysis mechanism of mixed-halide perovskites. We also show that photolysis renders the perovskite film more n-type without involving lead reduction. This study introduces a powerful methodology for quantitatively analyzing the mass loss kinetics of halide perovskites under both practical operational and accelerated aging conditions, offering deeper insights into the mechanisms of perovskite degradation.
Nanoscale Evolution of Charge Transport Through C–H···π Interactions
Yu Zhou - ,
Shurui Ji - ,
Yixuan Zhu - ,
Huanhuan Liu - ,
Juejun Wang - ,
Yanxi Zhang - ,
Jie Bai - ,
Xiaohui Li - ,
Jia Shi - ,
Wenqiu Su - ,
Ruiyun Huang - ,
Junyang Liu - , and
Wenjing Hong *
C–H···π interactions, a prevalent intermolecular force, play a pivotal role in chemistry, materials science, and life sciences. Despite extensive studies of their influence on intermolecular binding configurations and energetics, their impact on intermolecular coupling and charge transport remains unexplored. Here, we investigate the charge transport within supramolecular junctions connected by C–H···π and π–π interactions, respectively, and find that C–H···π interactions exhibit conductances that are 3.5 times those of π–π interactions. Angstrom-scale distance-dependent experiments indicate that the conductance of C–H···π supramolecular junctions experiences initial decay under stretching, followed by gradual convergence, in contrast with the periodic fluctuations in π–π stacked supramolecular junctions. Theoretical calculations show that charge transport within C–H···π interactions transitions from destructive to constructive quantum interference under stretching, with a larger range of constructive quantum interference compared with π–π stacking. This study establishes that C–H···π interactions facilitate efficient intermolecular charge transport and elucidates the evolution of quantum interference effects with assembly configuration, offering critical insights for the design of supramolecular materials and devices.
Two-Dimensional Superconductivity and Anomalous Vortex Dissipation in Newly Discovered Transition Metal Dichalcogenide-Based Superlattices
Mengzhu Shi - ,
Kaibao Fan - ,
Houpu Li - ,
Senyang Pan - ,
Jiaqiang Cai - ,
Nan Zhang - ,
Hongyu Li - ,
Tao Wu - ,
Jinglei Zhang - ,
Chuanying Xi - ,
Ziji Xiang *- , and
Xianhui Chen *
Properties of layered superconductors can vary drastically when thinned down from bulk to monolayer owing to the reduced dimensionality and weakened interlayer coupling. In transition metal dichalcogenides (TMDs), the inherent symmetry breaking effect in atomically thin crystals prompts novel states of matter such as Ising superconductivity with an extraordinary in-plane upper critical field. Here, we demonstrate that two-dimensional (2D) superconductivity resembling those in atomic layers but with more fascinating behaviors can be realized in the bulk crystals of two new TMD-based superconductors Ba0.75ClTaS2 and Ba0.75ClTaSe2 with superconducting transition temperatures 2.75 and 1.75 K, respectively. They comprise an alternating stack of H-type TMD layers and Ba–Cl layers. In both materials, intrinsic 2D superconductivity develops below a Berezinskii–Kosterlitz–Thouless transition. The upper critical field along the ab plane (Hc2||ab) exceeds the Pauli limit (μ0Hp); in particular, Ba0.75ClTaSe2 exhibits an extremely high μ0Hc2||ab≈ 14 μ0Hp and a colossal superconducting anisotropy (Hc2||ab/Hc2⊥ab) of ∼150. Moreover, the temperature-field phase diagram of Ba0.75ClTaSe2 under an in-plane magnetic field contains a large phase regime of vortex dissipation, which can be ascribed to the Josephson vortex motion, signifying an unprecedentedly strong fluctuation effect in TMD-based superconductors. Our results provide a new path toward the establishment of 2D superconductivity and novel exotic quantum phases in bulk crystals of TMD-based superconductors.
Mathematical Expression and Prediction of VOCs Adsorption Capacity and Isotherm
Zhongshen Zhang - ,
Wenqing Wu - ,
Gang Wang - ,
Yuan Wang - ,
Xinxin Wang - ,
Wenpeng Li - ,
Zeyu Zhao - ,
Xiaoxiao Duan - ,
Zhihao Zhang - ,
Chunli Wang - ,
Ganggang Li - ,
Guoxia Jiang - ,
Fenglian Zhang - ,
Jie Cheng - ,
Jinjun Li - ,
Chi He - , and
Zhengping Hao *
Adsorption capacity prediction, which needs to be based on the precise structure–capacity relationship, is important for better adsorbent design. However, the precise adsorption contribution coefficients of pores of different sizes for volatile organic compound (VOC) adsorption remain unclear. Herein, a control variable method is employed as a generative model to realize the numerization of the precise structure–capacity relationship. For the first time, a concise equation is proposed that can predict the adsorption capacities/isotherms of unknown adsorbents through their pore structure parameters. Interestingly, practical VOC adsorption amounts aligned with predicted values obtained by simultaneously considering pore volume (which undergoes volume-filling adsorption) and surface area (which undergoes surface-covering adsorption) as input variables. Derivation of the equation is based on classical adsorption theories and mathematical expression of the precise structure–capacity relationship obtained from actual experimental results. Each parameter in the equation has a specific physical meaning. This unprecedented VOC adsorption capacity/isotherm prediction method provides in-depth insight for accurate quantification of VOC adsorption, with great potential for gas adsorption prediction and guidance in the development of adsorption materials and technologies.
Ultracompact Electrical Double Layers at TiO2(110) Electrified Interfaces
Immad M. Nadeem - ,
Christopher Penschke - ,
Ji Chen - ,
Xavier Torrelles - ,
Axel Wilson - ,
Hadeel Hussain - ,
Gregory Cabailh - ,
Oier Bikondoa - ,
Jameel Imran - ,
Christopher Nicklin - ,
Robert Lindsay - ,
Jörg Zegenhagen - ,
Matthew O. Blunt - ,
Angelos Michaelides - , and
Geoff Thornton *
This publication is Open Access under the license indicated. Learn More
Metal-oxide aqueous interfaces are important in areas as varied as photocatalysis and mineral reforming. Crucial to the chemistry at these interfaces is the structure of the electrical double layer formed when anions or cations compensate for the charge arising from adsorbed H+ or OH–. This has proven extremely challenging to determine at the atomic level. In this work, we use a surface science approach, involving atomic level characterization, to determine the structure of pH-dependent model electrified interfaces of TiO2(110) with HCl and NaOH using surface X-ray diffraction (SXRD). A comparison with ab initio molecular dynamics calculations reveals the formation of surprisingly compact double layers. These involve inner-sphere bound Cl and Na ions, with respectively H+ and O–/OH– in the contact layer. Their exceptionally high electric fields will play a key role in determining the chemical reactivity.
Utilizing High X-ray Energy Photon-In Photon-Out Spectroscopies and X-ray Scattering to Experimentally Assess the Emergence of Electronic and Atomic Structure of ZnS Nanorods
Lars Klemeyer - ,
Tjark L. R. Gröne - ,
Cecilia de Almeida Zito - ,
Olga Vasylieva - ,
Melike Gumus Akcaalan - ,
Sani Y. Harouna-Mayer - ,
Francesco Caddeo - ,
Torben Steenbock - ,
Sarah-Alexandra Hussak - ,
Jagadesh Kopula Kesavan - ,
Ann-Christin Dippel - ,
Xiao Sun - ,
Andrea Köppen - ,
Viktoriia A. Saveleva - ,
Surender Kumar - ,
Gabriel Bester - ,
Pieter Glatzel - , and
Dorota Koziej *
This publication is Open Access under the license indicated. Learn More
The key to controlling the fabrication process of transition metal sulfide nanocrystals is to understand the reaction mechanism, especially the coordination of ligands and solvents during their synthesis. We utilize in situ high-energy resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) as well as in situ valence-to-core X-ray emission spectroscopy (vtc-XES) combined with density functional theory (DFT) calculations to identify the formation of a tetrahedral [Zn(OA)4]2+ and an octahedral [Zn(OA)6]2+ complex, and the ligand exchange to a tetrahedral [Zn(SOA)4]2+ complex (OA = oleylamine, OAS = oleylthioamide), during the synthesis of ZnS nanorods in oleylamine. We observe in situ the transition of the electronic structure of [Zn(SOA)4]2+ with a HOMO/LUMO gap of 5.0 eV toward an electronic band gap of 4.3 and 3.8 eV for 1.9 nm large ZnS wurtzite nanospheres and 2 × 7 nm sphalerite nanorods, respectively. Thus, we demonstrate how in situ multimodal X-ray spectroscopy and scattering studies can not only resolve structure, size, and shape during the growth and synthesis of NPs in organic solvents and at high temperature but also give direct information about their electronic structure, which is not readily accessible through other techniques.
Structure–Function Insights into Thermoresponsive Copolymers as Lanthanide Precipitants
Supraja S. Chittari - ,
Peter A. Dykeman-Bermingham - ,
Matthew P. Bogen - , and
Abigail S. Knight *
The synthetic toolbox for stimuli-responsive polymers has broadened to include many tunable variables, making these materials applicable in diverse technologies. However, unraveling the key composition–structure–function relationships to facilitate ground-up design remains a challenge due to the inherent dispersity in sequence and conformations for synthetic polymers. We here present a systematic study of these relationships using a model system of copolymers with a thermoresponsive (N-isopropylacrylamide) backbone in addition to metal-chelating (acrylic acid) and hydrophobic structural comonomers and evaluate their efficiency at isolating technologically critical lanthanide ions. The efficiency of lanthanide ion extraction by precipitation was quantitated with a metallochromic dye to reveal trends relating copolymer hydrophobicity to improved separations. Further, we examined the role of different hydrophobic comonomers in dictating the solution-phase conformation of the polymer in the presence and absence of lanthanide ions, and we correlated key features of the hydrophobic comonomer to extraction efficiency. Finally, we identified how the local proximity of thermoresponsive, chelating, and hydrophobic subunits facilitates metal extraction by manipulating the copolymer sequence with multiblock polymerization. Through mechanistic analysis, we propose a binding-then-assembly process through which metal ions are coprecipitated with macromolecular chelators.
Vibrational and Magnetic States of Point Defects in Bilayer MoSe2
Kai Fan - ,
Huimin Wang - ,
Ziwei Ma - ,
Wen-Ao Liao - ,
Wen-Hao Zhang - ,
Chao-Fei Liu - ,
Sheng Meng - ,
Guangjun Tian *- , and
Ying-Shuang Fu *
Defects in two-dimensional materials profoundly impact the physicochemical properties of the systems, whose characterization is highly desirable at the atomic scale. Here, using spectroscopic imaging scanning tunneling microscopy, we elucidate the vibrational and magnetic states of MoSe antisite and VMo vacancy with different charge states embedded in ultrathin MoSe2 bilayers supported on graphene substrate. Stringent vibronic states with multimode coupling are resolved on the defects. The spectral intensities are tunable with the electron tunneling rates and well-reproduced by theoretical modeling. Moreover, first-principles calculations suggest that the defects host a local magnetic moment of 2 μB in their neutral state, which is directly confirmed by our spin-flip inelastic electron tunneling spectroscopy. Our study deepens the understanding of defect properties and paves the way of defect-engineering material functionalities and spin-catalytic applications.
Understanding Pt Active Sites on Nitrogen-Doped Carbon Nanocages for Industrial Hydrogen Evolution with Ultralow Pt Usage
Jingyi Tian - ,
Minqi Xia - ,
Xueyi Cheng - ,
Chenghui Mao - ,
Yiqun Chen - ,
Yan Zhang - ,
Changkai Zhou - ,
Fengfei Xu - ,
Lijun Yang - ,
Xi-Zhang Wang *- ,
Qiang Wu *- , and
Zheng Hu *
Engineering microstructures of Pt and understanding the related catalytic mechanism are critical to optimizing the performance for hydrogen evolution reaction (HER). Herein, Pt dispersion and coordination are precisely regulated on hierarchical nitrogen-doped carbon nanocages (hNCNCs) by a thermal-driven Pt migration, from edge-hosted Pt–N2Cl2 single sites in the initial Pt1/hNCNC-70 °C catalyst to Pt clusters/nanoparticles and back to in-plane Pt–NxC4–x single sites. Thereinto, Pt–N2Cl2 presents the optimal HER activity (6 mV@10 mA cm–2) while Pt–NxC4–x shows poor HER activity (321 mV@10 mA cm–2) due to their different Pt coordination. Operando characterizations demonstrate that the low-coordinated Pt–N2 intermediates derived from Pt–N2Cl2 under the working condition are the real active sites for HER, which enable the multi-H adsorption mechanism with an ideal H* adsorption energy of nearly 0 eV, thereby the high activity, as revealed by theoretical calculations. In contrast, the high-coordinated Pt–NxC4–x sites only allow the single-H adsorption with a positive adsorption energy and thereby the low HER activity. Accordingly, with an ultralow Pt loading of only 25 μgPt cm–2, the proton exchange membrane water electrolyzer assembled using Pt1/hNCNC-70 °C as the cathodic catalyst achieves an industrial-level current density of 1.0 A cm–2 at a low cell voltage of 1.66 V and high durability, showing great potential applications.
A Complex Oxide Containing Inherent Peroxide Ions for Catalyzing Oxygen Evolution Reactions in Acid
Jie Dai - ,
Zihan Shen - ,
Yu Chen - ,
Mengran Li - ,
Vanessa K. Peterson - ,
Jiayi Tang - ,
Xixi Wang - ,
Yu Li - ,
Daqin Guan - ,
Chuan Zhou - ,
Hainan Sun - ,
Zhiwei Hu - ,
Wei-Hsiang Huang - ,
Chih-Wen Pao - ,
Chien-Te Chen - ,
Yinlong Zhu *- ,
Wei Zhou - , and
Zongping Shao *
Proton exchange membrane water electrolyzers powered by sustainable energy represent a cutting-edge technology for renewable hydrogen generation, while slow anodic oxygen evolution reaction (OER) kinetics still remains a formidable obstacle that necessitates basic comprehension for facilitating electrocatalysts’ design. Here, we report a low-iridium complex oxide La1.2Sr2.7IrO7.33 with a unique hexagonal structure consisting of isolated Ir(V)O6 octahedra and true peroxide O22– groups as a highly active and stable OER electrocatalyst under acidic conditions. Remarkably, La1.2Sr2.7IrO7.33, containing 59 wt % less iridium relative to the benchmark IrO2, shows about an order of magnitude higher mass activity, 6-folds higher intrinsic activity than the latter, and also surpasses the state-of-the-art Ir-based oxides ever reported. Combined electrochemical, spectroscopic, and density functional theory investigations reveal that La1.2Sr2.7IrO7.33 follows the peroxide-ion participation mechanism under the OER condition, where the inherent peroxide ions with accessible nonbonded oxygen states are responsible for the high OER activity. This discovery offers an innovative strategy for designing advanced catalysts for various catalytic applications.
Precisely Controlling the Activation of an Iron-Locked Drug Generator in the Liver Sinusoid to Enhance Barrier Penetration and Reduction of Liver Fibrosis
Quanwei Sun - ,
Wenshuo Yang - ,
Zhengwei Song - ,
Huiyu Lu - ,
Wencui Shang - ,
Huihui Li - ,
Zexin Yang - ,
Wenheng Gao - ,
Yunlong Li - ,
Yujing Xu - ,
Min Luo - ,
Kang Liu - ,
Qinghua Wu - ,
Zihua Xuan - ,
Wei Shen *- ,
Ye Yang *- , and
Dengke Yin *
Complex physical barriers and the nanomaterial’s clearance mechanism in the liver greatly hinder the feasibility of using a conventional liver-targeting nanoplatform to deliver antifibrotic drugs to pathological sites for the treatment of liver fibrosis. Here, a novel drug delivery strategy was designed to overcome drug penetration barriers in a fibrotic liver and cooperated with oral nattokinase (NKase)-mediated antifibrosis therapy as a proof of concept, which relies on the coadministration of a nanosized iron-locked drug generator (named Pro-HAase) and orally absorbed iron chelator deferasirox (DFX). Such a strategy starts from the rapid accumulation of intravenously injected Pro-HAase in the microcapillaries of the fibrotic liver followed by disrupting the polyphenol-iron coordination inside Pro-HAase by DFX, liberating antifibrotic components, including procyanidine (PA) and hyaluronidase (HAase). Attractively, absorption of DFX requires the sequential processes of traversing the intestinal mucosa and targeting the liver, which enable DFX to preferentially disassemble Pro-HAase accumulated in the liver sinusoid rather than in systemic circulation or other organs, thus avoiding the off-target activation of Pro-HAase and depletion of the normal iron pool. The in situ disassembly process decreases the sequestration of Pro-HAase by cells of the mononuclear phagocyte system and promotes gradient-driven permeation of therapeutic components to surrounding liver tissues within 2 h, accompanied by biliary excretion of the inactive iron-DFX complex. As a result, the cooperation of Pro-HAase and DFX not only allows NKase-mediated therapy to completely reverse liver fibrosis but also suppresses the chronic hepatotoxicity of residual liver iron after multiple doses of Pro-HAase. The high spatiotemporal precision, unique barrier-penetration mechanism, and self-detoxification ability of this strategy will inspire the rational design of analogous iron-locked nanosystems to improve the therapeutic outcomes of liver fibrosis or other liver diseases.
Unbuckling the 18-Crown-6 Ether Belt Around Metal Ions: Forging the Connection to the Condensed Phase
Ryu Sakuma - ,
Keisuke Hirata - ,
James M. Lisy *- ,
Masaaki Fujii *- , and
Shun-ichi Ishiuchi *
Crown ethers are central to supramolecular chemistry, recognizing and binding specific ions in solution. The most well-known, 18-Crown-6 (18C6), preferentially captures K+ in an aqueous solution, while gas phase binding of 18C6 with alkali metal ions decreases linearly with an increasing ionic radius. Why the high affinity for Li+ and Na+ in the gas phase is dramatically reduced with hydration remains an open question in understanding the K+ selectivity in the aqueous phase. A combined spectroscopic and computational study of M+18C6(H2O)n=0–3 (M = Li, Na, and K) in the CH stretch region has revealed how stepwise hydration unbuckles the crown ether belt from Li+ and Na+, substantially changing the backbone structure of 18C6. In contrast, the structure of the K+18C6 complex is unbuckled and is unaffected by hydration. Combined with new measurements of the OH stretch, a direct connection is provided between the stepwise hydration of M+18C6 and the selectivity for K+ in an aqueous solution. It demonstrates and validates at the molecular level the application of gas-phase measurements to condensed-phase studies.
Circular Engineered Sortase for Interrogating Histone H3 in Chromatin
Samuel D. Whedon - ,
Kwangwoon Lee - ,
Zhipeng A. Wang - ,
Emily Zahn - ,
Congcong Lu - ,
Maheeshi Yapa Abeywardana - ,
Louise Fairall - ,
Eunju Nam - ,
Sarah DuBois-Coyne - ,
Pablo De Ioannes - ,
Xinlei Sheng - ,
Adelina Andrei - ,
Emily Lundberg - ,
Jennifer Jiang - ,
Karim-Jean Armache - ,
Yingming Zhao - ,
John W. R. Schwabe - ,
Mingxuan Wu *- ,
Benjamin A. Garcia *- , and
Philip A. Cole *
This publication is Open Access under the license indicated. Learn More
Reversible modification of the histone H3 N-terminal tail is critical in regulating the chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here, we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless H3 tails onto nucleosomes. This approach significantly accelerates the production of both symmetrically and asymmetrically modified nucleosomes. We demonstrate the utility of asymmetrically modified nucleosomes produced in this way in dissecting the impact of multiple modifications on eraser enzyme processing and molecular recognition by a reader protein. Moreover, we show that cW11 sortase is very effective at cutting and tagging histone H3 tails from endogenous histones, facilitating multiplex “cut-and-paste” middle-down proteomics with tandem mass tags. This cut-and-paste proteomics approach permits the quantitative analysis of histone H3 modification crosstalk after treatment with different histone deacetylase inhibitors. We propose that these chemoenzymatic tail isolation and modification strategies made possible with cW11 sortase will broadly power epigenetic discovery and therapeutic development.
Alkanes C1–C6 C–H Bond Activation via a Barrierless Potential Energy Path: Trifluoromethyl Carbenes Enhance Primary C–H Bond Functionalization
Jonathan Martínez-Laguna - ,
Julia Altarejos - ,
M. Ángeles Fuentes - ,
Giuseppe Sciortino - ,
Feliu Maseras *- ,
Javier Carreras *- ,
Ana Caballero *- , and
Pedro J. Pérez *
This publication is Open Access under the license indicated. Learn More
In this mixed computational and experimental study, we report a catalytic system for alkane C1–C6 functionalization in which the responsible step for C–H bond activation shows no barrier in the potential energy path. DFT modeling of three silver-based catalysts and four diazo compounds led to the conclusion that the TpFAg═C(H)CF3 (TpF = fluorinated trispyrazolylborate ligand) carbene intermediates interact with methane without a barrier in the potential energy surface, a prediction validated by experimentation using N2═C(H)CF3 as the carbene source. The array of alkanes from propane to n-hexane led to the preferential functionalization of the primary sites with unprecedented values of selectivity for an acceptor diazo compound. The lack of those barriers implies that selectivity can no longer be controlled by differences in the energy barriers. Molecular dynamics calculations (with propane as the model alkane) are consistent with the preferential functionalization of the primary sites due to a higher concentration of such C–H bonds in the vicinity of the carbenic carbon atom.
Highly Efficient and Enantioselective Iridium-Catalyzed Asymmetric Reductive Cycloetherification
Yan Zong *- ,
Xiaomei Zou - ,
Hongqi Tao - ,
Qiuchen Huang - ,
Gen-Qiang Chen *- , and
Xumu Zhang *
A catalytic protocol for the iridium-catalyzed asymmetric hydrogenation (AH) of γ- or δ-hydroxy ketones to rapidly assemble various aliphatic enantioenriched tetrahydrofurans (THFs) or tetrahydropyrans (THPs) is disclosed. A wide range of enantioenriched THFs or THPs were obtained in high yields and excellent enantioselectivities (up to 99% and up to 96.5:3.5 er). The dynamic kinetic resolution asymmetric hydrogenation (DKR-AH) process was also achieved, simultaneously constructing enantioenriched THP scaffolds with two contiguous stereogenic centers with high yields and stereoselectivities (up to 92% yield, up to 98.5:1.5 er and >20:1 dr). Mechanistic investigation indicates that the key step of the reaction involves the AH of the challenging cyclic, aliphatic oxocarbenium ions. Furthermore, this catalytic enantioselective approach could be carried out on a gram scale, and various enantioenriched cyclic ethers were further transformed into an array of useful building blocks for enantioenriched natural products and bioactive molecules.
Crown-like Biodegradable Lipids Enable Lung-Selective mRNA Delivery and Dual-Modal Tumor Imaging In Vivo
Zhaoming Chen - ,
Yuexia Yang - ,
Xinyu Qiu - ,
Hao Zhou - ,
Rui Wang - , and
Hu Xiong *
Systemic mRNA delivery to specific cell types remains a great challenge. We herein report a new class of crown-like biodegradable ionizable lipids (CBILs) for predictable lung-selective mRNA delivery by leveraging the metal coordination chemistry. Each CBIL contains an impressive crown-like amino core that coordinates with various metal ions such as Zn2+ and further regulates the in vivo organ-targeting behavior of lipid nanoparticles (LNPs). The representative CBIL (Zn-9C-SCC-10)-formulated LNPs could exclusively deliver mRNA to the lung after systemic administration. Notably, following intravenous administration of 0.2 mg kg–1 Cre mRNA, Zn-9C-SCC-10 LNPs enabled the highly efficient gene editing of all lung epithelial and endothelial cells up to 43 and 61%, respectively, outperforming the current state-of-the-art LNPs in lung epithelial cell delivery. Moreover, compared to DLin-MC3-DMA LNPs with the addition of cationic lipid (DOTAP), our approach yielded a 44.6-fold enhancement in pulmonary mRNA expression and significantly improved biosafety in vivo. Taking advantage of paramagnetic gadolinium ion, Gd-12C-SCC-10 LNPs allowed the potent mRNA delivery to cancer cells and successfully illuminated lung tumors by magnetic and bioluminescent dual-mode imaging, facilitating the early discovery and diagnosis of lung cancer. This work will open a new avenue to rationally design predictable LNPs, as well as address the major challenges of mRNA delivery to specific cells in the lung tissues for treating a wide variety of diseases.
Copper-Iodide Hybrid Clusters with Partial Distortion Enable High-Performance Full-Visible-Spectrum White-Light-Emitting Diodes
Kuang-Hui Song - ,
Min Peng - ,
Jing-Jing Wang - ,
Li-Zhe Feng - ,
Yi-Chen Yin - ,
Yong-Hui Song - ,
Xue-Chen Ru - ,
Ya-Ping Xie - ,
Guozhen Zhang *- ,
Zhengtao Deng *- , and
Hong-Bin Yao *
Phosphor-converted white-light-emitting diodes (pc-WLEDs) have become increasingly prevalent artificial light sources. Currently, multicomponent phosphors are commonly used for pc-WLEDs, but they often suffer from issues of undesirable reabsorption and unstable emission colors. The potential alternative for pc-WLEDs is a single-component white phosphor that covers the broad visible spectrum with desirable low thermal quenching and efficient luminescence, which is still scarce. To address this challenge, we design a unique single-component white phosphor based on Cu4I4(4-(tert-butyl)-2-(diphenylphosphaneyl)pyridine)2 (Cu4I4(NP-tBu)2) hybrid clusters, which exhibits ultrabroad dual emission from 400 to 800 nm and a high photoluminescence quantum yield of 97% under 320 nm light excitation. Based on time-resolved fluorescence spectroscopy and theoretical model analysis of our Cu4I4 series clusters, we hypothesize that the dual emission comes from the coexistence of two triplet states caused by partial cluster distortion under light excitation. The Cu4I4(NP-tBu)2 cluster’s high structural stability also endows consistent spectral performance and low thermal quenching up to 240 °C. Thus, the fabricated pc-WLED using Cu4I4(NP-tBu)2 white phosphor exhibits a maximum efficiency of 63.4 lm/W and maintains a high color rendering index of ∼88 during 1000 h of continuous operation. Our results highlight a new strategy of low-cost and high-performance copper-iodide cluster-based single-component white phosphors for high-quality pc-WLEDs.
Stereoselective Glycosylation for 1,2-cis-Aminoglycoside Assembly by Cooperative Atom Transfer Catalysis
Hongze Li - ,
Dakang Zhang - ,
Chong Li - ,
Le Yin - ,
Zixiang Jiang - ,
Yunxuan Luo - , and
Hao Xu *
We report here a new catalytic method for exclusively 1,2-cis-α-selective glycosylation that assembles a wide variety of 1,2-cis-aminoglycosidic linkages in complex glycans and glycoconjugates. Mechanistic studies revealed a unique glycosylation mechanism in which the iron catalyst activates a glycosyl acceptor and an oxidant when it facilitates the cooperative atom transfer of both moieties to a glycosyl donor in an exclusively cis-selective manner. This catalytic approach is effective for a broad range of glycosyl donors and acceptors, and it can be operated in a reiterative fashion and scaled up to the multigram scale.
November 24, 2024
Origin of Performance Decline in Carbonated Anion Exchange Membrane Fuel Cells
Qihao Li - ,
Mihail R. Krumov - ,
Meixue Hu - ,
Colin R. Bundschu - ,
Li Xiao - ,
Lin Zhuang *- , and
Héctor D. Abruña *
Anion exchange membrane fuel cells (AEMFCs) have successfully eliminated anode carbonate precipitation through cation immobilization with the incorporation of alkaline polymer electrolytes (APEs). However, carbonation by CO2 in ambient air continues to induce significant AEMFC performance losses via mechanisms that remain unclear/elusive. In this multimodal investigation of AEMFC carbonation, we find that the increase in ionic resistance after carbonation accounts for only a small fraction of the cell voltage drop, especially at high current densities. Controlled anode and cathode carbonation tests indicated that the anode hydrogen oxidation reaction (HOR) was significantly impeded by carbonation. Hydrogen pump tests showed that the HOR kinetics were more than an order of magnitude lower after carbonation, thus accounting for the large decrease in the cell voltage. Further studies using the electrochemical quartz crystal microbalance (EQCM) revealed that there exists a large barrier to the rearrangement of the double layer at the Pt/ionomer interface in the hydrogen underpotential deposition (HUPD) region, which may explain the slower HOR kinetics after carbonation. These results provide fundamental insight into the unique properties of the catalyst/APE interface and suggest new directions for energy materials and technology developments.
Degradable and Piezoelectric Hollow ZnO Heterostructures for Sonodynamic Therapy and Pro-Death Autophagy
Lihan Cai - ,
Tao Sun - ,
Fuping Han - ,
Han Zhang - ,
Jiyu Zhao - ,
Qiao Hu - ,
Tiancong Shi - ,
Xiao Zhou - ,
Fang Cheng - ,
Chong Peng - ,
Ye Zhou - ,
Saran Long - ,
Wen Sun - ,
Jiangli Fan *- ,
Jianjun Du *- , and
Xiaojun Peng
Piezoelectric materials can generate charges and reactive oxygen species (ROS) under external force stimulation for ultrasound-induced sonodynamic therapy (SDT). However, their poor piezoelectricity, fast electron–hole pair recombination rate, and biological toxicity of piezoelectric materials limit the therapeutic effects of piezoelectric SDT. In this study, hollow ZnO (HZnO) nanospheres were synthesized by using a one-step method. The hollow structure facilitated the deformation of HZnO under stimulation by ultrasound mechanical force and increased the piezoelectric constant. Subsequently, black phosphorus quantum dots (BPQDs) and arginine-glycine-aspartic acid peptide (RGD)-poly(ethylene glycol) (PEG) were combined with HZnO to further enhance the piezoelectric effect by constructing heterojunctions and enable tumor-targeting ability. During treatment, HZnO-BPQDs-PEG could degrade in an acidic tumor microenvironment and release Zn2+ and PO43– ions to induce pro-death autophagy. The ROS produced by SDT also accelerated autophagy and promoted ferroptosis in cancer cells. This study demonstrates that HZnO-BPQDs-PEG has a strong piezoelectric SDT effect and can effectively induce autophagy in cancer cells, providing a new idea for the design and application of piezoelectric materials for tumor therapy.
November 23, 2024
Hydrogen Isotope Labeling of Pharmaceuticals Via Dual Hydrogen Isotope Exchange Pathways Using CdS Quantum Dot Photocatalyst
Rajendra Maity - ,
Otto Dungan - ,
Frédéric A. Perras - ,
Jingwei Li *- ,
Daohua Liu - ,
Sumei Ren - ,
Dan Lehnherr - ,
Zheng Huang - ,
Eric M. Phillips - ,
Moses Adeyemo - ,
Joseph Frimpong - ,
Timothy Quainoo - ,
Zhen-Fei Liu - , and
Long Luo *
Isotopic labeling is a powerful technique extensively used in the pharmaceutical industry. By tracking isotope-labeled molecules, researchers gain unique and invaluable insights into the pharmacokinetics and pharmacodynamics of new drug candidates. Hydrogen isotope labeling is particularly important as hydrogen is ubiquitous in organic molecules in biological systems, and it can be introduced effectively through late-stage hydrogen isotope exchange (HIE). However, hydrogen isotope methods that simultaneously label multiple sites with varying types of C–H bonds in the different types of molecules are still lacking. Herein, we demonstrate a heterogeneous photocatalytic system using a CdS quantum dot catalyst that proceeds via a unique dual HIE pathway mechanism─one occurs in the reaction solution and the other on the catalytic surface─to address it. This unique mechanism unlocked several unique labeling capabilities, including simultaneous labeling of multiple and challenging sites such as secondary α-amino, α-ethereal, allyl, and vinyl sites, providing great versatility in practical uses for pharmaceutical labeling.
November 22, 2024
Synthesis of Multisubstituted Cyclopentadiene Derivatives from 3,3-Disubstituted Cyclopropenes and Internal Alkynes Catalyzed by Low-Valent Niobium Complexes
Takuya Akiyama - ,
Tetsuro Kusamoto - ,
Kazushi Mashima - , and
Hayato Tsurugi *
A low-valent niobium species generated from NbCl5 and 1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene (Si-Me-CHD) in combination with PPh3 catalyzed a [2+2+1]-cycloaddition reaction of 3,3-disubstituted cyclopropenes and 2 equiv of diaryl/dialkylalkynes, leading to isomeric mixtures of multisubstituted cyclopentadienes 3–5. The initial catalyst activation process was a one-electron reduction of NbCl5 with Si-Me-CHD to provide [NbCl3(μ-Cl) (L)]2 (L = PMe2Ph (6), L = PPh3 (7)) in the presence of phosphine ligands. An NMR spectroscopic time course experiment using complex 7 as the catalyst revealed an induction period for the product formation, corresponding to an additional one-electron reduction of 7 by the substrates to give catalytically active η2-alkyne complexes of NbCl3. A combined computational and experimental study clarified the mechanism of this unprecedented [2+2+1]-cyclopentadiene synthesis; a rate-determining 1,2-insertion of cyclopropene into η2-alkyne niobium species to form cyclopropane-fused metallacyclopentene followed by ring-opening β-C elimination provides a dienylalkylidene intermediate prior to incorporation of the second alkyne through carbene/alkyne metathesis. We also demonstrated the synthetic utility of the multisubstituted cyclopentadienes as the cyclopentadienyl ligands by derivatizing to the corresponding lithium cyclopentadienide, which is applicable for the synthesis of ferrocene 10.
Molecular Design of Phthalocyanine-Based Drug Coassembly with Tailored Function
Dong Li - ,
Siyong Huang - ,
Jianlin Ge - ,
Ziqi Zhuang - ,
Longyi Zheng - ,
Lai Jiang - ,
Yulun Chen - ,
Chengchao Chu - ,
Yang Zhang - ,
Jie Pan - ,
Bingwei Cheng - ,
Jian-Dong Huang *- ,
Huirong Lin *- ,
Wei Han *- , and
Gang Liu *
Coassemblies with tailored functions, such as drug loading, tissue targeting and releasing, therapeutic and/or imaging purposes, and so on, have been widely studied and applied in biomedicine. De novo design of these coassemblies hinges on an integrated approach involving synergy between various design strategies, ranging from structure screening of combinations of “phthalocyanine-chemotherapeutic drug” molecules for molecular scaffolds, exploration of related fabrication principles to verification of intended activity of specific designs. Here, we propose an integrated approach combining computation and experiments to design from scratch coassembled nanoparticles. This nanocoassembly, termed NanoPC here, consists of phthalocyanine-based scaffolds hosting chemotherapeutic drugs, aimed at hypersensitive chemotherapy guided by photoimaging for targeting tumors. Our design starts from the selection of phthalocyanine derivatives that are not aggregation-prone, followed by computational screening of coassembled molecules covering various categories of chemotherapy drugs. To facilitate an efficient and accurate assessment of coassembly capabilities, we utilize small systems as surrogates to enable free-energy calculations at all-atom levels facilitated with enhanced sampling and statistical mechanics for efficient and accurate evaluation of coassembly ability. The final top NanoPC candidate, comprised of phthalocyanine PcL and cytarabine (CYT), can greatly increase the fluorescence intensity ratio of tumor/liver by 21.5 times and achieve higher antitumor efficiency in a pH-dependent manner. Therefore, the designing approach proposed here has a potential pattern, which can provide ideas and references for the design and development of coassembled nanodrugs with tailored functions and applications in biomedicine.
Exclusive Generation of Single-Atom Sulfur for Ultrahigh Quality Monolayer MoS2 Growth
Yunhao Zhang - ,
Jingwei Wang - ,
Yumo Chen - ,
Xian Wu - ,
Junyang Tan - ,
Jiarong Liu - ,
Huiyu Nong - ,
Liqiong He - ,
Qinke Wu - ,
Guangmin Zhou - ,
Xiaolong Zou - , and
Bilu Liu *
Preparation of high-quality two-dimensional (2D) transition metal dichalcogenides (TMDCs) is the precondition for realizing their applications. However, the synthesized 2D TMDCs (e.g., MoS2) crystals suffer from low quality due to the massive defects formed during the growth. Here, we report single-atom sulfur (S1) as a highly reactive sulfur species to grow ultrahigh-quality monolayer MoS2. Derived from battery waste, sulfurized polyacrylonitrile (SPAN) is found to be exclusive and efficient in releasing S1. The monolayer MoS2 prepared by SPAN exhibits an ultralow defect density of ∼7 × 1012 cm–2 and the narrowest photoluminescence (PL) emission peak with full-width at half-maximum of ∼47.11 meV at room temperature. Moreover, the statistical resonance Raman and low-temperature PL results further verify the significantly lower defect density and higher optical quality of SPAN-grown MoS2 than those of the conventional S-powder-grown samples. This work provides an effective approach for preparing ultrahigh-quality 2D single crystals, facilitating their industrial applications.
Generative Pretrained Transformer for Heterogeneous Catalysts
Dong Hyeon Mok - and
Seoin Back *
Discovery of novel and promising materials is a critical challenge in the field of chemistry and material science, traditionally approached through methodologies ranging from trial-and-error to machine-learning-driven inverse design. Recent studies suggest that transformer-based language models can be utilized as material generative models to expand the chemical space and explore materials with desired properties. In this work, we introduce the catalyst generative pretrained transformer (CatGPT), trained to generate string representations of inorganic catalyst structures from a vast chemical space. CatGPT not only demonstrates high performance in generating valid and accurate catalyst structures but also serves as a foundation model for generating the desired types of catalysts by text-conditioning and fine-tuning. As an example, we fine-tuned the pretrained CatGPT using a binary alloy catalyst data set designed for screening two-electron oxygen reduction reaction (2e-ORR) catalyst and generated catalyst structures specialized for 2e-ORR. Our work demonstrates the potential of generative language models as generative tools for catalyst discovery.
Plateau–Rayleigh Instability in Soft-Lattice Inorganic Solids
Zhen-Chao Shao - ,
Xianyun Jiang - ,
Chong Zhang - ,
Tianhao Wang - ,
Yan-Ru Wang - ,
Guo-Qiang Liu - ,
Zong-Ying Huang - ,
Yu-Zhuo Zhang - ,
Liang Wu - ,
Zhong-Huai Hou - ,
Huijun Jiang *- ,
Yi Li *- , and
Shu-Hong Yu *
Plateau–Rayleigh instability─a macroscopic phenomenon describing the volume-constant breakup of one-dimensional continuous fluids─has now been widely observed in adatoms, liquids, polymers, and liquid metals. This instability enables controlled wetting–dewetting behavior at fluid–solid interfaces and, thereby, the self-limited patterning into ordered structures. However, it has yet to be observed in conventional inorganic solids, as the rigid lattices restrict their “fluidity”. Here, we report the general fluid-like Plateau–Rayleigh instability of silver-based chalcogenide semiconductors featuring soft-lattice ionic crystals. It enables postsynthetic morphing from conformal core–shell nanowires to periodically coaxial ones. We reveal that such self-limited reconstruction is thermodynamically driven by the surface energy and interface energy and kinetically favored by the high ionic diffusion coefficients of subnanoscale soft-lattice shells. The resulting periodic heterostructures can be topotactically transformed for epitaxial combinations of functional semiconductors free from the lattice-matching rule. This fluid-like behavior in soft inorganic solids thus offers routes toward sophisticated nanostructures and controllable patterning at all-inorganic solid–solid interfaces.
Enantioselective Synthesis of vic-Aminoalcohol Derivatives by Nickel-Catalyzed Reductive Coupling of Aldehydes with Protected Amino-pentadienoates
Thilo Bender - and
Alois Fürstner *
This publication is Open Access under the license indicated. Learn More
A VAPOL-derived phosphoramidite ligand is uniquely effective at reverting the regiochemical course of nickel-catalyzed reactions of aldehydes with carbamate-protected 5-amino-2,4-pentadienoates as “push/pull” dienes; the ensuing carbonyl α-amino-homoallylation reaction affords anti-configured vic-aminoalcohol derivatives in good yields with high optical purity. The reductive coupling is conveniently performed with a bench-stable Ni(0) precatalyst and Et3B as the promoter.
Structural Disorder of a Layered Lithium Manganese Oxide Cathode Paving a Reversible Phase Transition Route toward Its Theoretical Capacity
Suwon Lee - ,
Seongkoo Kang - ,
Youngju Choi - ,
Jihyun Kim - ,
Junghoon Yang - ,
Daseul Han - ,
Kyung-Wan Nam - ,
Olaf J. Borkiewicz - ,
Jiliang Zhang - , and
Yong-Mook Kang *
Layered lithium manganese oxides suffer from irreversible phase transitions induced by Mn migration and/or dissolution associated with the Jahn–Teller effect (JTE) of Mn3+, leading to inevitable capacity fading during cycling. The popular doping strategy of oxidizing Mn3+ to Mn4+ to relieve the JTE cannot completely eliminate the detrimental structural collapse from the cooperative JTE. Therefore, they are considered to be impractical for commercial use as cathode materials. Here, we demonstrate a layered lithium manganese oxide that can be charged and discharged without any serious structural collapse using metastable Li-birnessite with controlled structural disorder. Although Li-birnessite is thermodynamically unstable under ambient conditions, Li ion exchange into Na-birnessite followed by an optimal dehydration resulted in a disordered Li-birnessite. The control over crystal water in the interlayer provides intriguing short-range order therein, which can help to suppress parasitic Mn migration and dissolution, thereby ensuring a reversible electrochemical cycling. The Mn redox behavior and local structure change of the Li-birnessite were investigated by ex situ soft X-ray absorption spectroscopy (sXAS) and X-ray pair distribution function (PDF) analysis. The combined sXAS and PDF with electrochemical analyses disclosed that the reversible Mn redox and suppressed phase transitions in Dh Li-birnessite contribute to dramatically improving its electrochemical reversiblity during cycling. Our findings underscore the substantial effects of controlled static disorder on the structural stability and electrochemical reversibility of a layered lithium manganese oxide, Li-birnessite, which extends the practical capacity of layered oxides close to their theoretical limit.
Oxygen Vacancy Boosts Nitrogen-Centered Radical Coupling Initiated by Primary Amine Electrooxidation
Mengwei Han - ,
Yongxiang Luo - ,
Leitao Xu - ,
Wei Chen *- ,
Chengmei Li - ,
Yu-Cheng Huang - ,
Yandong Wu - ,
Yimin Jiang - ,
Wenjie Wu - ,
Ruiqi Wang - ,
Ying-Rui Lu - ,
Yuqin Zou *- , and
Shuangyin Wang *
Synthesis of nitrogen-centered radicals (NCRs) for radical coupling reactions is a powerful and versatile tool in the arsenal of organic synthetic chemistry. However, there are few reports on the direct synthesis of NCRs based on aqueous electrocatalysis. Herein, we present a new electrochemical primary amine oxidation reaction (ePAOR) system with R1R2-CH-NH2 as the substrate for synthesizing NCRs and N–N coupling products. However, ePAOR on the model catalyst (NiO) suffers from low N–N coupling selectivity due to the weak adsorption energy of imine (R1R2-C═NH) intermediates. Guided by theoretical calculations, the oxygen vacancy gives NiO a strong adsorption capacity of R1R2-C═NH so that it boosts nitrogen-centered radical coupling initiated by the ePAOR on oxygen vacancy-rich NiO (VO-NiO), and the effective utilization rate of NCRs was increased from 36 to 75%. This approach is compatible with a wide range of primary amines and can be applied to N–N cross-coupling systems as well.
Covalent DNA-Encoded Library Workflow Drives Discovery of SARS-CoV-2 Nonstructural Protein Inhibitors
Xudong Wang - ,
Liwei Xiong - ,
Ying Zhu - ,
Sixiu Liu - ,
Wenfeng Zhao - ,
Xinyuan Wu - ,
Mengnisa Seydimemet - ,
Linjie Li - ,
Peiqi Ding - ,
Xian Lin - ,
Jiaxiang Liu - ,
Xuan Wang - ,
Zhiqiang Duan - ,
Weiwei Lu - ,
Yanrui Suo - ,
Mengqing Cui - ,
Jinfeng Yue - ,
Rui Jin - ,
Mingyue Zheng - ,
Yechun Xu - ,
Lianghe Mei *- ,
Hangchen Hu *- , and
Xiaojie Lu *
The COVID-19 pandemic, exacerbated by persistent viral mutations, underscored the urgent need for diverse inhibitors targeting multiple viral proteins. In this study, we utilized covalent DNA-encoded libraries to discover innovative triazine-based covalent inhibitors for the 3-chymotrypsin-like protease (3CLpro, Nsp5) and the papain-like protease (PLpro) domains of Nsp3, as well as novel non-nucleoside covalent inhibitors for the nonstructural protein 12 (Nsp12, RdRp). Optimization through molecular docking and medicinal chemistry led to the development of LU9, a nonpeptide 3CLpro inhibitor with an IC50 of 0.34 μM, and LU10, whose crystal structure showed a distinct binding mode within the 3CLpro active site. The X-ray cocrystal structure of SARS-CoV-2 PLpro in complex with XD5 uncovered a previously unexplored binding site adjacent to the catalytic pocket. Additionally, a non-nucleoside covalent Nsp12 inhibitor XJ5 achieved a potency of 0.12 μM following comprehensive structure–activity relationship analysis and optimization. Molecular dynamics revealed a potential binding mode. These compounds offer valuable chemical probes for target validation and represent promising candidates for the development of SARS-CoV-2 antiviral therapies.
Stenhouse Salts: Visible Light Photoswitches for Protic Environments
Derek Puthoff - ,
Hrishikesh Kuttiyil - , and
Julie A. Peterson *
Designing photoswitches that have large structural changes, are visible-light responsive, and are compatible with water is a major challenge for moving toward applications in biological systems. Despite the potential for Stenhouse salts to be a water-compatible counterpart to the popular DASA photoswitches, there has not yet been any major investigation into their properties as a photoswitch. Here, we report a series of aniline-based Stenhouse salt (AnSten) photoswitches with electron donating and withdrawing groups. AnSten photoswitches reversibly switch from a visible light absorbing isomer to a visible light transparent isomer upon irradiation with green light. The dark equilibrium and switching kinetics are dependent on the electronics of the aniline. These molecules switch reversibly in common protic solvents including water and hydrogels. Stenhouse salts show significant potential as a visible light active, water compatible, negative photochromic, T-type photoswitch with a large structural change.
Enantioselective Nickel-Electrocatalyzed Cross-Dehydrogenative α- and γ-Nitroalkylation
Juan Li - ,
Minghao Liu - ,
Boyuan Wei - ,
Lingzi Peng - ,
Jin Song *- , and
Chang Guo *
Asymmetric catalytic versions of electricity-driven processes hold immense potential for the sustainable preparation of chiral compounds. However, the involvement of anodic oxidative cross-dehydrogenative coupling events between two distinct nucleophiles makes it challenging for a chiral catalyst to regulate the stereochemistry of the products. Our current electrocatalytic strategy for enantioconvergent cross-dehydrogenative α- and γ-nitroalkylation via radical-based pathways produces an array of enantioenriched nitroesters without supplementary stoichiometric oxidants. Mechanistic investigations reveal that the nickel catalyst plays a key role in both the electrochemical activation of the substrates and the stereoselectivity-defining events, affording the electrochemically generated Lewis acid-bound α-carbonyl radicals to interact with in situ-generated nitronate anions in a stereoselective manner. This electrocatalytic approach enables transformations that are highly challenging under thermal conditions, such as umpolung reactivity with readily available substrates, all-carbon quaternary stereocenter creation, and the control of remote stereochemistry.
Charge Transfer Dynamics in Supramolecular Tessellations Composed of Aromatic Donors and Chiral Tris(naphthalenediimide) Triangular Acceptors
Malik L. Williams - ,
Jonathan R. Palmer - ,
Ryan M. Young - , and
Michael R. Wasielewski *
Understanding charge transfer (CT) dynamics in donor–acceptor (D–A) cocrystals is important for the development of efficient organic photovoltaic and electronic materials. This study explores the photogenerated CT states of supramolecular tessellations formed by cocrystallizing a chiral tris(naphthalenediimide) triangular prism (−)-NDI-Δ with pyrene, perylene, and peri-xanthenoxanthene electron donors. By manipulating crystallization conditions, one-dimensional (1D) and two-dimensional (2D) cocrystals with distinct structural motifs and morphologies are achieved. Femtosecond and nanosecond transient absorption microscopies and time-resolved electron paramagnetic resonance spectroscopy were employed to elucidate the CT state dynamics. Our findings reveal that the CT state lifetimes are lengthened in the 2D cocrystals relative to the 1D cocrystals, which is attributable to the symmetry and molecular packing differences between them that modulate the CT interactions. This work highlights the potential of using preorganized covalent multisite charge carriers as donors or acceptors in cocrystals as a strategy for engineering structures for advanced multifunctional materials with tunable CT properties.
Multistep Growth Pathway of Covalent Organic Framework Onion Nanostructures
Qi Zheng - ,
Amy Ren - ,
Alexandra Zagalskaya - ,
Haiyan Mao - ,
Daewon Lee - ,
Chongqing Yang - ,
Karen C. Bustillo - ,
Liwen F. Wan - ,
Tuan Anh Pham - ,
Jeffrey A. Reimer - ,
Jian Zhang - ,
Yi Liu - , and
Haimei Zheng *
The growth of complex organic macromolecular materials in solution is a pervasive phenomenon in both natural and synthetic systems, yet the underlying growth mechanisms remain largely unresolved. Using liquid-phase transmission electron microscopy (TEM), we elucidate the real-time growth pathways of covalent organic framework (COF) onion nanostructures, which involve graphitic layer formation, subsequent layer attachment, onion ring closure, and structural relaxation. This process is marked by variations in orientation and curvature, driven by the dynamic formation of the COF structure, which further regulates order–disorder transition and defect generation within the framework. Our in situ TEM characterizations provide valuable insights into how molecular arrangement drives the formation of complex nanostructures. We anticipate that direct imaging of COF nanostructure growth in liquids will open new opportunities for controlling COF crystal morphology, composition, and hierarchical structure development.
Spotlights on Recent JACS Publications, Volume 146, Issue 48
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November 21, 2024
Borane-Catalyzed Intermolecular Aryl Transfer between Hydrosilanes: Shifting the Equilibrium by Removal of a Gaseous Hydrosilane
Jiong Zhang - ,
Ximei Tian - ,
Yaqiong Wang - ,
Yin Zhang - ,
Fang Wang *- , and
Lipeng Wu *
The preparation of organosilanes is indeed far from trivial, despite their vast application. Herein, we report a straightforward and general hydrosilane iterative evolution system for the on-demand synthesis of heteroleptic-substituted hydrosilanes. A series of previously difficult-to-prepare hydrosilanes with two or three diverse substituents were readily obtained. Our process is achieved just by using a catalytic amount of BH3 to initiate a selective hydrosilane redistribution process via aryl group migration. Thus, our work represents sporadic examples of the application of hydrosilane redistribution procedures for synthetic applications, whereas hydrosilane redistribution is often found as an unwanted side reaction; its synthetic value has rarely been explored. Furthermore, an unprecedented and challenging cross-redistribution of aryl hydrosilanes with alkyl hydrosilanes is achieved. Mechanistic studies and density functional theory (DFT) calculations revealed that this process was attained via a BH3-catalyzed C–Si bond cleavage and selective intermolecular aryl group migration from aryl hydrosilanes to alkyl hydrosilanes.
Geminal Synergy in Pt–Co Dual-Atom Catalysts: From Synthesis to Photocatalytic Hydrogen Production
Aonan Zhu - ,
Yutao Cao - ,
Ning Zhao - ,
Yongcheng Jin - ,
Yonglong Li - ,
Ling Yang - ,
Cancan Zhang - ,
Yangxuan Gao - ,
Zhao Zhang - ,
Yuying Zhang - , and
Wei Xie *
Dual-atom catalysts (DACs) have garnered significant interest due to their high atom utilization and synergistic catalysis. However, developing a precise synthetic method for DACs and comprehending the underlying catalytic mechanisms remain challenging. In this study, we employ a photoinduced anchoring strategy to precisely synthesize PtCo DAC on graphitic carbon nitride (CN). A Co atom was anchored on CN through the lone-pair electrons of nitrogen. Upon light irradiation, photoelectrons gathering at the Co site can anchor Pt metal ions nearby, accurately facilitating the formation of heteronuclear DACs. The PtCo DAC demonstrates a remarkably high H2 generation rate from ammonia borane (AB) hydrolysis, with a TOF of 3130 molH2 molPt–1 min–1 at 298 K. This TOF value is approximately 3.2 times higher than that of the Pt single-atom photocatalyst. Importantly, the PtCo DAC shows good stability, achieving a turnover number as high as 307,982 molH2 molPt–1 at room temperature. The experimental and theoretical calculation results demonstrate that the synergy between Pt and Co optimizes the adsorption energy of AB and H2 molecules while reducing the energy barrier of the rate-determining step, thus accelerating H2 evolution from AB hydrolysis. Additionally, the introduced Co species stabilize the Pt active sites by enhancing the stability of the Pt–N bond, preventing leaching, aggregation, and deactivation. The excellent catalytic performance, good stability, and low cost of the catalysts in this work open new prospects for their practical application in hydrogen production.
Remote-Contact Catalysis for Target-Diameter Semiconducting Carbon Nanotube Arrays
Jiangtao Wang *- ,
Xudong Zheng - ,
Gregory Pitner - ,
Xiang Ji - ,
Tianyi Zhang - ,
Aijia Yao - ,
Jiadi Zhu - ,
Tomás Palacios - ,
Lain-Jong Li - ,
Han Wang - , and
Jing Kong *
Electrostatic catalysis uses an external electric field (EEF) to rearrange the charge distribution to boost reaction rates and selectively produce certain reaction products in small-molecule reactions (e.g., Diels–Alder addition), requiring a 10 MV/cm field aligned with the reaction axis. Such a large and oriented EEF is challenging for large-scale implementation or material growth with multiple reaction axes or steps. Here, we demonstrate that the energy band at the tip of an individual single-walled carbon nanotube (SWCNT) can be spontaneously shifted in a high-permittivity growth environment, with its other end in contact with a low-work-function electrode (e.g., hafnium carbide). By adjusting the Fermi level at a point where there is a substantial disparity in the density of states (DOS) between semiconducting (s-) and metallic (m-) SWCNTs, we achieve effective electrostatic catalysis for 99.92% purity s-SWCNT growth with a narrow diameter distribution (0.95 ± 0.04 nm), targeting the requirement of advanced SWCNT-based electronics for future computing.
Enhancing the Conversion Efficiency of Polyethylene to Methane through Codoping of Mn Atoms into Ru Centers and CeO2 Supports
Meng Zhao - ,
Xiang Chu - ,
Fei Wang - ,
Yizhu Fang - ,
Lu Sun - ,
Qing Xie - ,
Ling-ling Zhang - ,
Shuyan Song *- ,
Hongjie Zhang - , and
Xiao Wang *
Chemical conversion has emerged as an effective approach for disposing waste plastics; however, the product diversity in traditional methods leads to pressing challenges in product separation and purification. As a pioneering advancement, the comprehensive transformation of waste plastics into CH4 presents an attractive prospect: directly yielding high-purity products. Significantly, CH4 is an important hydrogen carrier and an industrial feedstock. However, there is still much room for enhancing the overall efficiency. Herein, we show a new strategy to construct a high-efficiency and robust polyethylene (PE) upgrading catalyst by codoping Mn heteroatoms into both RuO2 and CeO2. We found that these Mn heteroatoms effectively bolster the stability of Ruδ+ species under high-temperature reduction conditions. The harmonious coexistence of Ru0 and Ruδ+ significantly refines the reaction pathway by enhancing the adsorption of the alkane intermediates. Consequently, we achieved an impressive PE conversion rate exceeding >99% with nearly 99% toward CH4 at a moderate temperature of 250 °C within 8 h. Our discovery not only opens a new window for catalyst upgrading but also presents exciting opportunities for the in-depth conversion of waste plastics into complex, high-purity fine chemicals through methane-mediated catalysis.
Phosphonate-Based Aza-Macrocycle Ligands for Low-Temperature, Stable Chelation of Medicinally Relevant Rare Earth Radiometals and Radiofluorination
Jennifer N. Whetter - ,
Dariusz Śmiłowicz - ,
Kaelyn V. Becker - ,
Eduardo Aluicio-Sarduy - ,
Cormac A. A. Kelderman - ,
Angus J. Koller - ,
Owen M. Glaser - ,
Axia Marlin - ,
Shin Hye Ahn - ,
Margarita N. Kretowicz - ,
Jonathan W. Engle - , and
Eszter Boros *
Radioisotopes of fluorine (18F), scandium (43/44Sc, 47Sc), lutetium (177Lu), and yttrium (86Y, 90Y) have decay properties ideally suited for targeted nuclear imaging and therapy with small biologics, such as peptides and antibody fragments. However, a single-molecule strategy to introduce these radionuclides into radiopharmaceuticals under mild conditions to afford inert in vivo complexes is critically lacking. Here, we introduce H4L2 and H4L3, two small-cavity macrocyclic chelator structural isomers bearing a single phosphonate functional group. Potentiometry and spectrophotometry were employed to determine H4L2 and H4L3′s ability to form a single [M(L)]− species with metals of different sizes (Sc3+, Lu3+, and Y3+) under physiologically relevant conditions. NMR spectroscopy and density functional theory (DFT) calculations suggest modulation of H4L2 and H4L3′s inner-sphere hydration across the Sc3+/Lu3+/Y3+ series. Radiochemical labeling experiments with 18F, 44Sc, 177Lu, and 86Y reveal that H4L2 selectively chelates radioscandium at room temperature with high apparent molar activity (AMA, 462 mCi/μmol), while radiofluorination remains inaccessible. In contrast, H4L3 enables room temperature radiochelation 44Sc, 177Lu, and 86Y (AMA: 96–275 mCi/μmol) and incorporates 18F via the Sc–18F methodology to form [18F][ScF(L3)]2–. In vivo biodistribution analysis at 1 h postinjection confirms the broad utility of H4L3: all four radiochemical complexes clear off-target organs and remain >98% intact in urine metabolite analyses. The scope of room temperature radiochemical labeling, paired with facile 18F incorporation, to afford in vivo compatible complexes exceeds the clinical gold standard chelator DOTA and previously reported acyclic chelators, rendering H4L3 promising for prospective radiopharmaceutical applications.
DNA-Regulated Multi-Protein Complement Control
Yinglun Ma - ,
Peter H. Winegar - ,
C. Adrian Figg - ,
Namrata Ramani - ,
Alex J. Anderson - ,
Kathleen Ngo - ,
John F. Ahrens - ,
Nikhil S. Chellam - ,
Young Jun Kim - , and
Chad A. Mirkin *
In nature, the interactions between proteins and their complements/substrates can dictate complex functions. Herein, we explore how DNA on nucleic acid modified proteins can be used as scaffolds to deliberately control interactions with a peptide complement (by adjusting length, sequence, and rigidity). As model systems, split GFPs were covalently connected through DNA scaffolds (36–58 bp). Increasing the length or decreasing the rigidity of the DNA scaffold (through removal of the duplex) increases the extent of intramolecular protein binding (up to 7.5-fold) between these GFP fragments. Independent and dynamic control over functional outputs can also be regulated by DNA hybridization; a multi-protein (split CFP and YFP) architecture was synthesized and characterized by fluorescence. This ternary construct shows that DNA displacement strands in different stoichiometric ratios can be used deliberately to regulate competitive binding between two unique sets of proteins. These studies establish a foundation for creating new classes of biological machinery based upon the concept of DNA-regulated multi-protein complement control.
Performance Descriptor of Subsurface Metal-Promoted Boron Catalysts for Low-Temperature Propane Oxidative Dehydrogenation to Propylene
Xiaofeng Gao - ,
Cheng Cai - ,
Shuheng Tian - ,
Shiqiang Xu - ,
Lili Lin *- ,
Jinan Shi - ,
Chuqiao Song - ,
Tao Wang *- ,
Ding Ma *- , and
Siyu Yao *
Boron-based catalysts have exhibited excellent olefin selectivity in the oxidative dehydrogenation of propane (ODHP) reaction. The substrate material should be a potential platform for performance modulation of boron catalysts in this reaction since the introduction of subsurface Ni promoters significantly improves the activity. In this study, we deciphered the substrate effect and identified a performance descriptor to comprehend the roles of subsurface materials in BOx/metal/BN ODHP catalysts by evaluating different metal promoters. Performance evaluation and transient infrared spectroscopic experiments demonstrate that the intrinsic activity and kinetic behaviors of the O–H bond dissociation/regeneration on the metal-promoted BOx overlayer are metal substrate-dependent. Combining density functional theory (DFT) calculations, it is found that the dissociation/regeneration inclination of the O–H bond in BOx(OH)3–x active species is controlled by the affinity of H for boron oxide species. The metal-O binding energy, which has been demonstrated to be linearly correlated with H affinity, can serve as a straightforward performance descriptor for both low-temperature radical initialization and ODHP reaction, revealing this reaction is controlled by the Sabatier principle, and moderate metal-O binding energy is essential for achieving remarkable performance in the BOx/M/BN catalysts. Following the guidance of a potential descriptor, Ni–Rh alloy substrates are investigated and the substrate with a Ni/Rh molar ratio of 15:1 significantly enhances the low-temperature intrinsic activity of the metal-modified BOx to 9.26 μmol/(m2·s), which reaches 105.9 times that of h-BN and is 18.3% larger than the monometallic BOx/Ni/BN catalysts.
Melt Alloying of Two-Dimensional Hybrid Perovskites: Composition-Dependence of Thermal and Optical Properties
Arad Lang *- ,
Celia Chen - ,
Chumei Ye - ,
Lauren N. McHugh - ,
Xian Wei Chua - ,
Samuel D. Stranks - ,
Siân E. Dutton - , and
Thomas D. Bennett
This publication is Open Access under the license indicated. Learn More
Melt alloying, the process of melting a physical powder blend to create a homogeneous alloy, is widely used in materials processing. By carefully selecting the materials and their proportions, the physical properties of the resulting alloy can be precisely controlled. In this study, we investigate the possibility of utilizing melt alloying principles for meltable two-dimensional hybrid organic–inorganic perovskites (2D-HOIPs). We blend and melt mixtures of two selected 2D-HOIPs: the glass-forming (S-NEA)2PbBr4 (S-NEA = (S)-(−)-1-(1-naphthyl)ethylammonium) and the liquid-forming (1-MHA)2PbI4 (1-MHA = 1-methylhexylammonium). Upon melting and cooling, 1-MHA-poor blends (X1-MHA ≤ 50% mol, where X1-MHA corresponds to the relative molar concentration of (1-MHA)2PbI4 in the blend) form a hybrid glass, while 1-MHA-rich blends (X1-MHA ≥ 70% mol) crystallize. The melting temperature of all blends, as well as the glass transition temperature of the glass-forming blends, change according to blend composition. In all cases, melting produces a homogeneous structure, either glassy or crystalline, which remains such after the glassy samples are recrystallized upon a second heat treatment. This method enables band gap tuning of the blends, given that it varies with composition and crystallinity. Overall, this work demonstrates the applicability of classical melt processing to binary-component functional hybrid systems, and paves the way to solvent-free perovskite-based device fabrication.
Activation of Methyltrioxorhenium for Olefin Metathesis by a Frustrated Lewis Pair
Yannick Stöferle - ,
Péter Pál Kalapos - ,
Patrik Willi - , and
Peter Chen *
Methyltrioxorhenium (MTO) supported on Al2O3 or SiO2–Al2O3 is an efficient heterogeneous alkene metathesis catalyst that works at room temperature and tolerates various functional groups. Surface studies found that MTO interacts with highly Lewis-acidic aluminum centers and that its methyl group is probably C–H activated resulting in rhenium-methylidene species. The exact structure of the catalyst resting state and the active species is subject to scientific debate. Here, we report on the activation of MTO by 2,6-lutidine and tris(pentafluorophenyl)borane (B(C6F5)3), a frustrated Lewis pair (FLP) in solution. The MTO/FLP catalyst is active in ring-opening metathesis polymerization of norbornene and in cross-metathesis of internal olefins under mild conditions. ESI-MS and NMR studies found that MTO is deprotonated in the presence of the FLP to yield a rhenium-methylidene species. While this initially activated methylidene eluded detection, spraying reaction mixtures with structurally constrained olefins in ESI-MS allowed for the detection of on-cycle rhenium-alkylidene species. Time-course measurements showed that the modest catalytic activity could be attributed to a rapid catalyst deactivation step. One possible deactivation pathway was identified to be a second deprotonation step of the metathesis-active methylidene, yielding a rhenium-methylidyne. Kinetic experiments have shown that it can be reactivated for olefin metathesis by protonation in solution. Additionally, several irreversible catalyst deactivation pathways leading to permanently deactivated catalyst species are hypothesized. We propose that the MTO/FLP system constitutes a homogeneous model system for the heterogeneous MTO catalysts.
Dynamic Creation of a Local Acid-like Environment for Hydrogen Evolution Reaction in Natural Seawater
Deyu Bao - ,
Linsen Huang - ,
Yingjie Gao - ,
Kenneth Davey - ,
Yao Zheng *- , and
Shi-Zhang Qiao *
Electrolysis of natural seawater driven by renewable energy is practically attractive for green hydrogen production. However, because precipitation initiated by an increase in local pH near to the cathode deactivates catalysts or blocks electrolyzer channels, limited catalysts are capable of operating with untreated, natural seawater (viz., pH 8.2 to 8.3 and ca. 35 g salts L–1); most are used in strongly alkaline or acidic seawater. Here, we report a new natural seawater electrolysis cathode with precipitation-suppression via a Pt/WO2 catalyst to create a dynamically local acid-like environment. The in situ formed hydrogen tungsten bronze (HxWOy) phase via continuous hydrogen insertion from water acts as a proton reservoir. As a result, dynamically stored protons create a local acid-like environment near the Pt active sites. We evidence that this tailored acid-like environment boosts the hydrogen evolution reaction in natural seawater splitting and neutralizes generated OH– species to restrict precipitation formations. Consequently, a long-term stability of >500 h at 100 mA cm–2 was exhibited in direct seawater electrolysis.
Axial Chlorination Engineering of Single-Atom Nanozyme: Fe-N4Cl Catalytic Sites for Efficient Peroxidase-Mimicking
Shengjie Wei - ,
Minmin Sun - ,
Juan Huang - ,
Zhengbo Chen *- ,
Xijun Wang *- ,
Lizeng Gao *- , and
Jijie Zhang *
Developing axial coordination engineering of single-atom nanozymes (SAzymes), directly regulating the axial coordination environment of the catalytic site, and optimizing the axial adsorption are meaningful and challenging for boosting the enzyme-like activities. Herein, the axial chlorination engineering of SAzyme with the Fe-N4Cl catalytic site (Fe-N4Cl/CNCl) was first proposed, exhibiting superior peroxidase-like activity compared to the traditional Fe-N4/CN SAzyme with Fe-N4 site. The maximal reaction velocity (4.73 × 10–5 M min–1), the catalytic constant (246.4 min–1), and the specific activity (81 U/mg) catalyzed by the Fe-N4Cl/CNCl SAzyme were 4.9 times, 3.9 times, and 2.7 times those of the Fe-N4/CN SAzyme, revealing the enormous advantages of axial chlorination engineering of SAzymes for remarkably improving enzyme-like activities. Moreover, the Fe-N4Cl/CNCl SAzyme also exhibited an enhanced inhibition effect of tumor cell growth in vitro and in vivo. The density functional theory calculation revealed that the Fe-N4Cl site was more favorable for releasing •OH radical, lowering the energy barrier of rate-determining step, and accelerating the reaction rate compared to the Fe-N4 site. This work demonstrated the outstanding potential of axial chlorination engineering of SAzymes for improving enzyme-like activities and practical application in tumor therapy.
Triggering the Dual-Metal-Site Lattice Oxygen Mechanism with In Situ-Generated Mn3+ Sites for Enhanced Acidic Oxygen Evolution
Jianyun Liu - ,
Tanyuan Wang *- ,
Mingzi Sun - ,
Mengyi Liao - ,
Shiyu Wang - ,
Shuxia Liu - ,
Hao Shi - ,
Yang Liu - ,
Yue Shen - ,
Ruiguo Cao - ,
Yunhui Huang - ,
Bolong Huang *- , and
Qing Li *
The development of high-performance non-Ir/Ru catalysts for the oxygen evolution reaction (OER) in acid is critical for the applications of proton exchange membrane water electrolyzers (PEMWEs). Here, we report a new kind of heterostructure catalyst by loading 5.8% Ag nanoparticles on MnO nanorods (Ag/MnO) for acidic OER. The as-prepared Ag/MnO requires only an overpotential of 196 mV for the OER at a current density of 10 mA cm–2 in 0.5 M H2SO4 and operates in a PEMWE for over 300 h at a current density of 200 mA cm–2, representing one of the best non-Ir/Ru OER catalysts. Operando X-ray absorption spectroscopy confirms that the introduction of trace Ag can promote the generation of highly active Mn3+–O sites with oxygen vacancies at a low voltage, leading to a dual-metal-site lattice oxygen-mediated pathway with faster kinetics than the adsorbate evolution mechanism. Theoretical calculations indicate that the trace Ag promotes the overlap between the d orbitals of Mn and the s, p orbitals of O, thereby activating the lattice oxygen and reducing the OER energy barrier. The dissolution of Mn is also suppressed by Ag due to the increased energy for vacancy formation of Mn, where the stability number reaches a high value of 3058, supporting improved structural stability.
November 20, 2024
Retraction of “Set of Cytochrome P450s Cooperatively Catalyzes the Synthesis of a Highly Oxidized and Rearranged Diterpene-Class Sordarinane Architecture”
Qibin Chen *- ,
Guanyin Yuan - ,
Tao Yuan - ,
Huiting Zeng - ,
Zheng-Rong Zou - ,
Zong-cai Tu - ,
Jie Gao *- , and
Yi Zou *
This publication is free to access through this site. Learn More
Spatial Control over Reactions via Localized Transcription within Membraneless DNA Nanostar Droplets
Eli Kengmana - ,
Elysse Ornelas-Gatdula - ,
Kuan-Lin Chen - , and
Rebecca Schulman *
Biomolecular condensates control where and how fast many chemical reactions occur in cells by partitioning reactants and catalysts, enabling simultaneous reactions in different spatial locations of a cell. Even without a membrane or physical barrier, the partitioning of the reactants can affect the rates of downstream reaction cascades in ways that depend on reaction location. Such effects can enable systems of biomolecular condensates to spatiotemporally orchestrate chemical reaction networks in cells to facilitate complex behaviors such as ribosome assembly. Here, we develop a system for developing such control in synthetic systems. We localize different transcription templates within different phase-separated, membraneless DNA nanostar (NS) droplets─programmable, in vitro liquid–liquid phase separation systems for partitioning of substrates and localization of reactions to membraneless droplets. When RNA produced within such droplets is also degraded in the bulk, droplet-localized transcription creates RNA concentration gradients. Consistent with the formation of these gradients, toehold-mediated strand displacement reactions involving transcripts are 2-fold slower far from the site of transcription than when nearby. We then demonstrate how multiple such gradients can form and be maintained independently by simultaneous transcription reactions occurring in tandem, each localized to different NS droplet types. Our results provide a means for constructing reaction systems in which different reactions are spatially localized and controlled without the need for physical membranes. This system also provides a means for generally studying how localized reactions and the exchange of reaction products might occur between protocells.
Facile Alkyne Assembly-Enabled Functional Au Nanosheets for Photoacoustic Imaging-Guided Photothermal/Gene Therapy of Orthotopic Glioblastoma
Xixi Hu - ,
Peiling Li - ,
Dongdong Xu - ,
Hua Liu - ,
Qiaoqiao Hao - ,
Mengyang Zhang - ,
Zhaoyin Wang *- ,
Tianxiang Wei *- , and
Zhihui Dai *
Treatment of glioblastoma (GBM) remains challenging due to the presence of blood–brain barrier (BBB) and tumor heterogeneity. Herein, Au nanosheets (AuNSs) functionalized with RGD peptides and small interfering RNA (siRNA), referred to as AuNSs-RGD-C≡C-siRNA (ARCR), are prepared to achieve multimodal therapy for GBM. The AuNSs with a large modifiable surface area, intriguing photothermal conversion efficiency (50.26%), and remarkable photothermal stability (44 cycles over 7 h) are created using a well-designed amphiphilic surfactant. Furthermore, alkynyl groups are assembled onto the Au surface within 1 min, enabling strong covalent binding of siRNA to AuNSs and thereby avoiding the interference from biological thiols. Owing to the lipophilicity of the surfactant and the targeting property of RGD, ARCR effectively passes through the BBB and accumulates in GBM tumor regions, allowing near-infrared photoacoustic imaging-guided photothermal/gene therapy. This work proposes a facile strategy to construct theranostic Au-based materials, highlighting the potential of multifunctional nanoagents for GBM therapy.
Temperature-Programmed Desorption of Single Zeolite Nanoparticles
Xuannuo Yi - ,
Shasha Liu - ,
Taotao Zhao - ,
Xiangke Guo - ,
Kai Zhou - ,
Weiping Ding - , and
Wei Wang *
Zeolites are essential solid acid catalysts in various chemical processes. Temperature-programmed desorption (TPD) is one of the most established techniques used to characterize the acidity of zeolites by measuring the desorption kinetics of probes from bulk samples. However, conventional TPD can hardly deliver the intrinsic acid properties of zeolites because the apparent desorption kinetics are inevitably mixed with mass transfer and thermal conduction due to the large sample amount (∼0.1 g). Herein, we developed an optical microscopy approach to measure the TPD spectra of single zeolite nanoparticles, termed oTPD, by in situ monitoring of the reduced scattering intensity of individuals as a result of the desorption of probe molecules during heating. A significantly reduced sample amount contributed to the oTPD spectrum, revealing an intrinsic desorption temperature of ∼300 °C lower than the apparent value and also a greatly narrowed peak width from ∼150 to ∼15 °C. Correlating oTPD and micro-Raman spectra of the very same individuals further uncovered a linear dependence between the acidity and the content of silicon islands. This study provided unprecedented capabilities for measuring the intrinsic acid properties and the desorption kinetics of single zeolite nanoparticles, with implications for better understanding the structure–acidity relationship and for designing better zeolite catalysts.
Preserving High Porosity of Covalent Organic Frameworks via Functional Polymer Guest Introduction
Tianwei Xue - ,
Olga A. Syzgantseva - ,
Li Peng *- ,
Ruiqing Li - ,
Yuyu Guo - ,
Chengbin Liu - ,
Tongxin Qiao - ,
Wenli Hao - ,
Jiaran Li - ,
Lilin Zhu - ,
Shuliang Yang *- ,
Jun Li *- , and
Wendy L. Queen *
Due to their high structural tunability, remarkable internal surface areas, readily accessible pore space, and host of possible applications, covalent organic frameworks (COFs) remain at the forefront of materials science research. Unfortunately, many COFs suffer from structural distortions or pore collapse during activation, which can lead to a substantial loss of crystallinity and functionality. Thus, herein, we demonstrate a facile method to address this issue by introducing polymer guests. The polymer adheres to the COF internal pore wall, acting as a supporting pillar during activation and effectively preserving the COF porosity and crystallinity. In fact, the surface area of one COF/polymer composite, known as TAPB-TA/PDA, was boosted by a factor of 16 when compared to the parent COF, TAPB-TA. More importantly, the now robust COF structure was able to resist layer shifting and order loss during both solvent immersion and removal. The introduction of functional polymer guests not only solidifies the COF structure and preserves its high porosity but is also shown to enhance the transport and separation of photogenerated charge carriers, thereby facilitating hydrogen evolution during photocatalytic water splitting. Molecular dynamics simulations further support experimental observations that the incorporation of PDA within the COF pores reinforces the walls, preventing its collapse. The proposed mechanism is based on the adsorption of PDA oligomers along the c direction of the unit cell, fastening the COF layers in place via van der Waals interactions. This kind of interaction locks −N═CH–Ph–CH═N– units in a trans-configuration in the COF pores.
Kinetic Modeling Enables Understanding of Off-Cycle Processes in Pd-Catalyzed Amination of Five-Membered Heteroaryl Halides
Elaine Reichert Raguram *- ,
Jakob C. Dahl *- ,
Klavs F. Jensen - , and
Stephen L. Buchwald
The mechanism of Pd-catalyzed amination of five-membered heteroaryl halides was investigated by integrating experimental kinetic analysis with kinetic modeling through predictive testing and likelihood ratio analysis, revealing an atypical productive coupling pathway and multiple off-cycle events. The GPhos-supported Pd catalyst, along with the moderate-strength base NaOTMS, was previously found to promote efficient coupling between five-membered heteroaryl halides and secondary amines. However, slight deviations from the optimal concentration, temperature, and/or solvent resulted in significantly lower yields, contrary to typical reaction optimization trends. We found that the coupling of 4-bromothiazole with piperidine proceeds through an uncommon mechanism in which the NaOTMS base, rather than the amine, binds first to the oxidative addition complex; the resulting OTMS-bound Pd species is the resting state. Formation of the Pd-amido complex via base/amine exchange was identified as the turnover-limiting step, unlike other reported catalyst systems for which reductive elimination is turnover-limiting. We determined that the amine-bound Pd complex, usually an on-cycle intermediate, is instead a reversibly generated off-cycle species, and that base-mediated decomposition of 4-bromothiazole is the primary irreversible catalyst deactivation pathway. Predictive testing and kinetic modeling were key to the identification of these off-cycle processes, providing insight into minor mechanistic pathways that are difficult to observe experimentally. Collectively, this report reveals the unique enabling features of the Pd-GPhos/NaOTMS system, implementing mechanistic insights to improve the yields of particularly challenging coupling reactions. Moreover, these findings highlight the utility of applying predictive tests to kinetic models for the rapid evaluation of mechanistic possibilities in small-molecule catalytic systems.
Functionalized Graphene via a One-Pot Reaction Enabling Exact Pore Sizes, Modifiable Pore Functionalization, and Precision Doping
Kira Coe-Sessions - ,
Alathea E. Davies - ,
Bhausaheb Dhokale - ,
Michael J. Wenzel - ,
Masoumeh Mahmoudi Gahrouei - ,
Nikiphoros Vlastos - ,
Jordan Klaassen - ,
Bruce A. Parkinson - ,
Laura de Sousa Oliveira *- , and
John O. Hoberg *
This publication is Open Access under the license indicated. Learn More
Functionalizing graphene with exact pore size, specific functional groups, and precision doping poses many significant challenges. Current methods lack precision and produce random pore sizes, sites of attachment, and amounts of dopant, leading to compromised structural integrity and affecting graphene’s applications. In this work, we report a strategy for the synthesis of functionalized graphitic materials with modifiable nanometer-sized pores via a Pictet–Spengler polymerization reaction. This one-pot, four-step synthesis uses concepts based on covalent organic frameworks (COFs) synthesis to produce crystalline two-dimensional materials that were confirmed by PXRD, TEM measurements, and DFT studies. These new materials are structurally analogous to doped graphene and graphene oxide (GO) but, unlike GO, maintain their semiconductive properties when fully functionalized.
A Multifunctional Peptide Nucleic Acid/Peptide Copolymer-Based Dual-Mode Biosensor with Macrophage-Hitchhiking for Enhanced Tumor Imaging and Urinalysis
Kaiji Wei - ,
Yu Xu - ,
Cunpeng Nie - ,
Qiaomei Wei - ,
Ping Xie - ,
Tingting Chen *- ,
Jianhui Jiang - , and
Xia Chu *
Biosensors are capable of diagnosing tumors through imaging in vivoor liquid biopsy, but they face the challenges of inefficient delivery into tumor sites and the lack of reliable tumor-associated biomarkers. Herein, we constructed a dual-mode biosensor based on a multifunctional peptide nucleic acid (PNA)/peptide copolymer and DNA tetrahedron for tumor imaging and urinalysis. The biosensor could enter the cancer cells to initiate a microRNA-21-specific catalytic hairpin assembly reaction after cleavage by matrix-metalloprotease (MMP) in the tumor microenvironment, and the MMP cleavage product was released into the bloodstream and then was filtered out by the kidney. As PNA was a synthetic DNA analogue that could not be degraded by nucleases and proteases, it could serve as a reliable synthetic biomarker and be easily detected by high-performance liquid chromatography in urine. Importantly, the biosensor was hitchhiked on the macrophage membrane to realize efficient delivery in the depth of tumor utilizing the macrophage ability of actively homing to the tumor site and infiltrating into the tumor. The results indicated that the signal output of the biosensor was improved remarkably and mice with a tumor volume as little as 30–40 mm3 could be reliably discriminated through urine assay. This innovative macrophage-hitchhiking dual-mode biosensor holds a great potential as a non-invasive and convenient tool for tumor diagnosis and tumor progression evaluation.
An Open-Shell Functionalization of Inorganic Benzene
Sabrina Grenda *- ,
Nicolas Claiser - ,
Antonio Barbon - ,
Frédéric Guégan - ,
Bérangère Toury - , and
Dominique Luneau *
A borazine derivative functionalized by nitroxide free radicals, N,N′,N″-(tris(4-Bromophenyl))-B,B′,B″-tris((2,6-dimethyl-4-(N-tert-butyl-N-oxyamino)phenyl) borazine (TriBNit), was synthesized as a milestone of open-shell inorganic benzene. The crystal structure determined from X-ray diffraction on a single crystal ascertains the grafting of three nitroxide radicals. The temperature dependence of the magnetic susceptibility evidences weak intramolecular antiferromagnetic interactions between the radicals with strong intermolecular antiferromagnetic interactions between two nitroxide moieties of two neighboring molecules. EPR spectroscopy at 80 K on a frozen glassy solution evidences the coexistence of S = 1/2 and S = 3/2 ground-spin state species. This is ascribed to the nitroxide radicals having different orientations with respect to the borazine core giving rise either to antiferromagnetic interaction with a low ground-spin state S = 1/2 or to ferromagnetic interaction with a high ground-spin state S = 3/2 as supported by theoretical data. At room temperature, because of nitroxide mobility, the EPR spectrum is averaged to a ground-spin state S = 1/2.
Molecular Complexity-Inspired Synthetic Strategies toward the Calyciphylline A-Type Daphniphyllum Alkaloids Himalensine A and Daphenylline
Brandon A. Wright - ,
Taku Okada - ,
Alessio Regni - ,
Guilian Luchini - ,
Shree Sowndarya S. V - ,
Nattawadee Chaisan - ,
Sebastian Kölbl - ,
Sojung F. Kim - ,
Robert S. Paton *- , and
Richmond Sarpong *
In this report, we detail two distinct synthetic approaches to calyciphylline A-type Daphniphyllum alkaloids himalensine A and daphenylline, which are inspired by our analysis of the structural complexity of these compounds. Using MolComplex, a Python-based web application that we have developed, we quantified the structural complexity of all possible precursors resulting from one-bond retrosynthetic disconnections. This led to the identification of transannular bonds as especially simplifying to the molecular graph, and, based on this analysis, we pursued a total synthesis of himalensine A from macrocyclic intermediates with planned late-stage transannular ring formations. Despite initial setbacks in accessing an originally designed macrocycle, targeting a simplified macrocycle ultimately enabled investigation of this intermediate’s unique transannular reactivity. Given the lack of success to access himalensine A based solely on molecular graph analysis, we revised our approach to the related alkaloid, daphenylline. Herein, we also provide the details of the various synthetic challenges that we encountered and overcame en route to a total synthesis of daphenylline. First, optimization of a Rh-mediated intramolecular Buchner/6π-electrocyclic ring-opening sequence enabled construction of the pentacyclic core. We then describe various attempts to install a key quaternary methyl group and, ultimately, our solution to leverage a [2 + 2] photocycloaddition/bond cleavage sequence to achieve this elusive goal. Finally, a late-stage Friedel–Crafts cyclization and deoxygenation facilitated the 11-step total synthesis, which was made formally enantioselective by a Rh-mediated dihydropyridone conjugate arylation. Complexity analysis of the daphenylline synthesis highlights how complexity-building/C–C cleavage combinations can be uniquely effective in achieving synthetic outcomes.
Nanoscale Mixed-Ligand Metal–Organic Framework for X-ray Stimulated Cancer Therapy
Wenyao Zhen - ,
Ziwan Xu - ,
Yibin Mao - ,
Caroline McCleary - ,
Xiaomin Jiang - ,
Ralph R. Weichselbaum - , and
Wenbin Lin *
Concurrent localized radiotherapy and systemic chemotherapy are standards of care for many cancers, but these treatment regimens cause severe adverse effects in many patients. Herein, we report the design of a mixed-ligand nanoscale metal–organic framework (nMOF) with the ability to simultaneously enhance radiotherapeutic effects and trigger the release of a potent chemotherapeutic under X-ray irradiation. We synthesized a new functional quaterphenyl dicarboxylate ligand conjugated with SN38 (H2QP-SN) via a hydroxyl radical-responsive covalent linkage. Because of the similar length of QP-SN and bis(p-benzoato)porphyrin (DBP) ligands, QP-SN was incorporated into Hf-DBP nMOF to afford a novel multifunctional mixed-ligand Hf-DBP-QP-SN nMOF with good biocompatibility. Hf-DBP-QP-SN not only enhances radiation damage to tumors via a unique radiotherapy-radiodynamic therapy (RT-RDT) process but also increases ·OH generation from radiolysis with electron-dense Hf12 secondary building units (SBUs) to release SN38 from Hf-DBP-QP-SN for chemotherapy. Elevated levels of hydrogen peroxide in the tumor microenvironment further stimulate the release of SN38 by enhancing ·OH generation under X-ray irradiation. With low doses of X-ray irradiation, Hf-DBP-QP-SN suppressed the growth of CT26 colon and 4T1 breast tumors by 93.5% and 95.2%, respectively, without any sign of general toxicity. Our study highlights the potential of using ionizing radiation-mediated chemistry for on-demand activation of nanotherapeutics for synergistic radiotherapy and chemotherapy without causing severe adverse effects.
Ligand-Directed Valence Band Engineering in Pb2+ Hybrid Crystals: Achieving Dispersive Bands and Shallow Valence Band Maximum
Daiki Umeyama *- and
Soshi Iimura
While crystalline hybrid solids hold great potential as novel semiconductors, most semiconductive hybrids utilize transition metal ions, which inherently limit carrier mobility due to the small band dispersion derived from the d orbitals. The filled s orbitals of post-transition metal ions offer the potential to design dispersed valence bands, but a method to translate the local structure design of these metal ions to valence band engineering is still in development. This study focuses on Pb2+-containing hybrid crystals, developing a simple strategy to control the Pb2+ coordination geometry through the molecular design of azole ligands. By preprogramming the coordination number of Pb2+ with azolate ligands, we succeeded in obtaining an isotropic coordination environment at a higher coordination number, resulting in a dispersed valence band and shallow valence band maximum while having a wide band gap. Detailed analysis of the band structures reveals that the energy levels and symmetry of the molecular orbitals of the anions play important roles in realizing these antinomic properties. This ligand-directed approach achieves both isotropy and covalency in the coordination bond by exploiting the diversity of the molecular orbitals. Our findings provide a foundation for future design strategies to optimize electronic structures in hybrid materials, advancing their application in semiconductive devices.
Retraction of “Two-Dimensional Violet Phosphorus P11: A Large Band Gap Phosphorus Allotrope”
Gary Cicirello - ,
Mengjing Wang - ,
Quynh P. Sam - ,
James L. Hart - ,
Natalie L. Williams - ,
Huabing Yin - ,
Judy J. Cha - , and
Jian Wang
This publication is free to access through this site. Learn More
Homologation of Carboxylic Acids Using a Radical-Polar Conjunctive Reagent
Jonathan N. Gruhin - ,
Richard Kim - ,
Aristidis Vasilopoulos - ,
Eric A. Voight - , and
Erik J. Alexanian *
Homologations of organic molecules that add a carbon atom to the substrate are useful in drug discovery to access compounds with improved properties that otherwise present a synthetic challenge. Carboxylic acids are present in many bioactive molecules and are widely available building blocks for chemical synthesis, yet their direct homologation is unknown. This valuable transformation currently necessitates implementation of multistep processes that require the use of carboxylic acid derivatives rather than the native substrates, and commonly involves highly reactive and toxic reagents. Herein, we report the first one-step homologation directly from native carboxylic acids using a novel, bench-stable (1-phosphoryl)vinyl sulfonate reagent under mild conditions. This strategy was applied to a wide range of aliphatic carboxylic acid building blocks and biologically relevant complex molecules to access an array of ester, amide, and carboxylic acid homologues in a single step. The (1-phosphoryl)vinyl sulfonate reagent participates in complementary homologation protocols featuring either radical-chain transfer or organic photoredox catalysis and introduces a new synthon, the distonic acylium radical, for molecular diversification. We anticipate this strategy, which addresses a long-standing challenge in organic synthesis, will expedite drug discovery by enabling the rapid synthesis of diversified homologues.
Rhodium-Catalyzed Asymmetric Reductive Hydroformylation of α-Substituted Enamides
Yuxin Zhu - ,
Yuchen Zhang - ,
Dongyang He - ,
He Yang *- ,
Xiao-Song Xue *- , and
Wenjun Tang *
Chiral γ-amino alcohols are prevalent structural motifs in natural products and bioactive compounds. Nevertheless, efficient and atom-economical synthetic methods toward enantiomerically enriched γ-amino alcohols are still lacking. In this study, a highly enantioselective rhodium-catalyzed reductive hydroformylation of readily available α-substituted enamides is developed, providing a series of pharmaceutically valuable chiral 1,3-amino alcohols in good yields and excellent enantioselectivities in a single step. The development of the 4,4′-bisarylamino-substituted BIBOP ligand is crucial for the success of this transformation. DFT calculations and experimental data have revealed the importance of hydrogen bonding between the N–H group in the structure of TFPNH-BIBOP and the enamide carbonyl group in promoting both high enantioselectivity and reactivity. This method has enabled the concise synthesis of several chiral pharmaceutical intermediates including a single-step synthesis of the key chiral intermediate of maraviroc.
Nuclear Quantum Effects in Quantum Mechanical/Molecular Mechanical Free Energy Simulations of Ribonucleotide Reductase
Mathew Chow - ,
Clorice R. Reinhardt - , and
Sharon Hammes-Schiffer *
The enzyme ribonucleotide reductase plays a critical role in DNA synthesis and repair. Its mechanism requires long-range radical transfer through a series of proton-coupled electron transfer (PCET) steps. Nuclear quantum effects such as zero-point energy, proton delocalization, and hydrogen tunneling are known to be important in PCET. We present a strategy for efficiently incorporating nuclear quantum effects into multidimensional free energy surfaces and real-time dynamical simulations for condensed-phase systems such as enzymes. This strategy is based on the nuclear–electronic orbital (NEO) method, which treats specified protons quantum mechanically on the same level as the electrons. NEO density functional theory (NEO-DFT) is combined with the quantum mechanical/molecular mechanical finite temperature string method with umbrella sampling via a simple reweighting procedure. Application of this strategy to PCET between two tyrosines, Y731 and Y730, in ribonucleotide reductase illustrates that nuclear quantum effects could either raise or lower the free energy barrier, leading to a range of possible kinetic isotope effects. Real-time time-dependent DFT (RT-NEO-TDDFT) simulations highlight nuclear–electronic quantum dynamics. These approaches enable the incorporation of nuclear quantum effects into a wide range of chemically and biologically important processes.
Iron-Catalyzed Cross-Electrophile Coupling for the Formation of All-Carbon Quaternary Centers
Andria L. Pace - ,
Felix Xu - ,
Wei Liu - ,
Marissa N. Lavagnino - , and
David W. C. MacMillan *
Quaternary carbon centers are desirable targets for drug discovery and complex molecule synthesis, yet the synthesis of these motifs within traditional cross-coupling paradigms remains a significant challenge due to competing β-hydride elimination pathways. In contrast, the bimolecular homolytic substitution (SH2) mechanism offers a unique and attractive alternative pathway. Metal porphyrin complexes have emerged as privileged catalysts owing to their ability to selectively form primary metal–alkyl complexes, thereby eliminating the challenges associated with tertiary alkyl complexation with a metal center. Herein, we report an iron-catalyzed cross-electrophile coupling of tertiary bromides and primary alkyl electrophiles for the formation of all-carbon quaternary centers through a biomimetic SH2 mechanism.
November 19, 2024
Conditionally Activatable Chimeras for Tumor-Specific Membrane Protein Degradation
Hongxiang Liu - ,
Zhijiang Fu - ,
Yu Han - ,
Yike Fang - ,
Weijun Shen - ,
Zhicheng Chen - ,
Rongfeng Zhu - ,
Heng Zhang *- , and
Peng R. Chen *
The recent advancements on membrane protein degraders (MPDs) have broadened the applicability of proteolysis-targeting chimeras (PROTACs) beyond intracellular proteins to include the previously “undruggable” cell-surface targets. However, the potential toxicity of MPDs caused by undesired off-target degradation poses a significant challenge to clinical deployment, mirroring concerns associated with PROTACs. Here, we introduce a conditionally activatable membrane protein degrader (Pro-MPD), which leverages the specificity and high affinity of biparatopic nanobodies combined with a tumor microenvironment-activated cell-penetrating peptide (Pro-CPP) to achieve on-target activated internalization and degradation of PD-L1 within tumor sites. This modularly designed Pro-MPD demonstrated a high target degradation efficiency and T cell reactivation, as well as sustained inhibition of tumor growth in xenograft models, highlighting its potential as a safer and highly efficient MPD for in vivo applications. Our work provides a general strategy for the development of conditionally activatable MPDs, which offers a new avenue for reducing the undesired systemic toxicity of MPDs due to the off-tumor degradation.
Reticular Chemistry for Enhancing Bioentity Stability and Functional Performance
Mengchu Feng - ,
Chunyan Xing - ,
Yehao Jin - ,
Xiao Feng - ,
Yuanyuan Zhang *- , and
Bo Wang *
Addressing the fragility of bioentities that results in instability and compromised performance during storage and applications, reticular chemistry, specifically through metal–organic frameworks (MOFs) and covalent organic frameworks (COFs), offers versatile platforms for stabilization and enhancement of bioentities. These highly porous frameworks facilitate efficient loading and mass transfer, offer confined environments and selective permeability for stabilization and protection, and enable finely tunable biointerfacial interactions and microenvironments for function optimization, significantly broadening the applications of various bioentities, including enzymes, nucleic acids, cells, etc. This Perspective outlines strategies for integrating bioentities with reticular frameworks, highlighting new design ideas for existing issues within these strategies. It emphasizes the crucial roles of these frameworks for bioentities in enhancing stability, boosting activity, imparting non-native functions, and synergizing bioentity systems. Concluding with a discussion of the challenges and prospects in the design, characterization, and practical applications of these biocomposites, this Perspective aims to inspire further development of high-performance biocomposites in this promising field.
A Unified Phosphoramidite Platform for the Synthesis of Morpholino Oligonucleotides and Diverse Chimeric Backbones
Atanu Ghosh - ,
Arpan Banerjee - ,
Shalini Gupta - , and
Surajit Sinha *
Phosphorodiamidate Morpholino Oligonucleotides (PMOs) have been well established in the milieu of FDA-approved oligonucleotide-based drugs in the past decade. Given their relevance in antisense therapeutics, a DNA/RNA synthesizer-compatible modular synthesis protocol of PMOs is long awaited to explore next-generation PMO chimeras with other therapeutically proven oligonucleotide backbones. Herein, we demonstrate a streamlined 5′ → 3′phosphoramidite approach for the synthesis of PMOs using tert-butyl-protected 5′-tBu-morpholino phosphoramidites, which were synthesized from 5′–OH morpholino monomers derived from commercially available ribonucleosides. 2-Cyanoethyl (CE)-protected 5′-CE-morpholino phosphoramidites were also synthesized to generate thiophosphoramidate (TMO) and phosphoramidate (MO) morpholino oligonucleotides. Full-length PMOs and TMOs in exceptional overall yields were obtained with operational simplicity and compatibility with automated DNA/RNA synthesizers utilizing controlled pore glass (CPG) as the solid support and CH3CN as the solvent. Importantly, this method has opened the possibility of designing various biologically relevant ASO design modalities, such as PMO-TMO and PMO-MO, which were inaccessible otherwise. Moreover, DNA nucleotides were also incorporated to generate PMO-psDNA and PMO–DNA using commercially available 5′-DNA phosphoramidites. The biophysical properties of all synthesized oligonucleotides were analyzed using UV melting and circular dichroism studies. The serum interaction profile and innate immune response of the PS-modified polythymidine oligonucleotides were analyzed and it was found that the mixed backbone oligonucleotides had a balanced profile compared to fully charged or neutral extremities. Overall, the synthesis is amenable to fast generation of various types of PMO chimeras for biological screening, which will expedite their therapeutic exploration and transition to clinic.
Photocatalytic Substrate Oxidation Catalyzed by a Ruthenium(II) Complex with a Phenazine Moiety as the Active Site Using Dioxygen as a Terminal Oxidant
Tomoya Ishizuka - ,
Taichiro Nishi - ,
Nanase Namura - ,
Hiroaki Kotani - ,
Yasuko Osakada - ,
Mamoru Fujitsuka - ,
Yoshihito Shiota - ,
Kazunari Yoshizawa - , and
Takahiko Kojima *
This publication is Open Access under the license indicated. Learn More
We have developed photocatalytic oxidation of aromatic substrates using O2 as a terminal oxidant to afford only 2e–-oxidized products without the reductive activation of O2 in acidic water under visible-light irradiation. A RuII complex (1) bearing a pyrazine moiety as the active site in tetrapyrido[3,2-a:2′,3′-c:3″,2″-h:2‴,3‴-j]phenazine (tpphz) as a ligand was employed as a photocatalyst. The active species for the photocatalysis was revealed to be not complex 1 itself but the protonated form, 1-H+, protonated at the vacant diimine site of tpphz. Upon photoexcitation in the presence of an organic substrate, 1-H+ was converted to the corresponding dihydro-intermediate (2-H+), where the pyrazine moiety of the ligand received 2e– and 2H+ from the substrate. 2-H+ was facilely oxidized by O2 to recover 1-H+. Consequently, an oxidation product of the substrate and H2O2 derived from dioxygen reduction were obtained; however, the H2O2 formed was also used for oxidation of 2-H+. In the oxidation of benzyl alcohol to benzaldehyde, the turnover number reached 240 for 10 h, and the quantum yield was determined to be 4.0%. The absence of ring-opening products in the oxidation of cyclobutanol suggests that the catalytic reaction proceeds through a mechanism involving formal hydride transfer. Mechanistic studies revealed that the photocatalytic substrate oxidation by 1-H+ was achieved in neither the lowest singlet excited state nor triplet excited state (S1 or T1) but in the second lowest singlet excited state (S2), i.e., 1(π–π*)* of the tpphz ligand. Thus, the photocatalytic substrate oxidation by 1-H+ can be categorized into unusual anti-Kasha photocatalysis.
Solid-State Electrochemical Carbon Dioxide Capture by Conductive Metal–Organic Framework Incorporating Nickel Bis(diimine) Units
Jinxin Liu - ,
Mingyu Yang - ,
Xinyi Zhou - , and
Zheng Meng *
This paper presents the first implementation of electrically conductive metal–organic framework (MOF) Ni3(2,3,6,7,10,11-hexaiminotriphenylene)2 (Ni3(HITP)2) integrated with nickel bis(diimine) (Ni-BDI) units for efficient solid-state electrochemical carbon dioxide (CO2) capture. The electrochemical cell assembled using Ni3(HITP)2 as working electrodes can reversibly capture and release CO2 through potential control. A high-capacity utilization of 96% and a Faraday efficiency of 98% have been achieved. The material also exhibits excellent electrochemical stability with its capacity maintained during 50 capture–release cycles and resistance to general interferences, including O2, H2O, NO2, and SO2. Capacity utilization of up to 35% is obtained at CO2 concentrations as low as 1%. The capture of CO2 at concentrations ranging from 1% to 100% requires exceptionally low energy consumption of only 30.5–72.4 kJ mol–1. Studies combining spectroscopic experiments and computational approaches reveal that the CO2 capture and release mechanism involves reversible carbamate formation on the N atom of the Ni-BDI unit in the MOF upon its one-electron redox reaction.
Rapid Exploration of Chemical Space by High-Throughput Desorption Electrospray Ionization Mass Spectrometry
Kai-Hung Huang - ,
Nicolás M. Morato - ,
Yunfei Feng - ,
Alexis Toney - , and
R. Graham Cooks *
This publication is Open Access under the license indicated. Learn More
This study leverages accelerated reactions at the solution/air interface of microdroplets generated by desorption electrospray ionization (DESI) to explore the chemical space. DESI is utilized to synthesize drug analogs at an overall rate of 1 reaction mixture per second, working on the low-nanogram scale. Transformations of multiple drug molecules at specific functionalities (phenol, hydroxyl, amino, carbonyl, phenyl, thiophenyl, and alkenyl) are achieved using electrophilic/nucleophilic, redox, C–H functionalization, and coupling reactions. These transformations occur under ambient conditions on the millisecond time scale with direct detection of products being successful in all but three of the reaction types studied. The large scope (22 bioactive compounds, >20 chemical transformations, and >300 functionalization reagents) and high speed (>3000 reactions/hour) provide access to a wide array of drug analogs that can be used for bioactivity testing. A total of ∼6800 unique reactions were examined through a data-driven workflow, and more than 3000 unique derivatives (∼44%) were identified tentatively by the m/z value and signal-to-control ratio in single-stage mass spectrometry (MS) analysis, with over 1000 being further characterized by tandem MS. The speed of the DESI-MS reaction screen provides potential advantages for emerging machine learning-based predictions of organic synthesis, and it sets the stage for future online DESI-MS bioassays and scaled-up microdroplet synthesis before formal characterization of hit compounds is sought using traditional methods of drug discovery.
N–H Bond Activation of Ammonia by a Redox-Active Carboranyl Diphosphine
Amanda L. Humphries - ,
Gabrielle A. Tellier - ,
Mark D. Smith - ,
Anthony R. Chianese *- , and
Dmitry V. Peryshkov *
In this work, we report the room-temperature N–H bond activation of ammonia by the carboranyl diphosphine 1-PtBu2-2-PiPr2-closo-C2B10H10 (1) resulting in the formation of zwitterionic 7-P(NH2)tBu2-10-P(H)iPr2-nido-C2B10H10 (2). Unlike the other phosphorus-based ambiphiles that require geometric constraints to enhance electrophilicity, the new mode of bond activation in this main-group system is based on the cooperation between electron-rich trigonal phosphine centers and the electron-accepting carborane cluster. As an exception among many other metal-based and metal-free systems, the N–H bond activation of gaseous ammonia or aqueous ammonium hydroxide by carboranyl diphosphine 1 proceeds with tolerance of air and water. Mechanistic details of ammonia activation were explored computationally by DFT methods, demonstrating an electrophilic activation of ammonia by the phosphine center. This process is driven by the reduction of the boron cluster followed by an ammonia-assisted deprotonation and proton transfer. A subsequent reaction of 2 and TEMPO results in the cleavage of all N–H and P–H bonds with the formation of a cyclic phosphazenium cation supported by an anionic cluster N(7-PtBu2-8-PiPr2)-nido-C2B9H10 (3). Transformations reported herein represent the first example of ammonia oxidation via triple hydrogen atom abstraction facilitated by a metal-free system.
Accelerated Exploration of Empty Material Compositional Space: Mg–Fe–B Ternary Metal Borides
Zhen Zhang - ,
Shiya Chen - ,
Feng Zheng - ,
Vladimir Antropov - ,
Yang Sun *- , and
Kai-Ming Ho
Borides are a family of materials with valuable properties for various applications. Their diverse structures and compositions, yet disparity in the constituent chemical elements for the known compounds, give elemental substitutions for prototypes great potential for material discovery. To explore uncharted material compositional space, we develop a workflow that joins high-throughput crystal structure prediction and automated diffraction pattern matching to discover new compounds with significant prediction and synthesis hurdles. Utilizing the workflow, we explore the empty Mg–Fe–B ternary compositional space, previously uncharted largely due to the immiscibility of Mg and Fe, as a paradigm. A total of 275 ternary boride prototypes are classified, using which we predict 23 (158) stable and metastable ternary phases within 50 (200) meV/atom above the convex hull. We identify Gd2(FeB)7-type Mg2Fe7B7 and ZrCo3B2-type MgFe3B2 to match previously unsolved experimental powder X-ray diffraction (PXRD) patterns. The discovered Mg2Fe7B7 and related channeled structures feature mismatched Mg and (FeB) sublattice periods, for which we conduct structural analyses with respect to the PXRD. They are predicted to exhibit exceptionally fast superionic transport of Mg and outstanding electrochemical performance, which serve as post-Li-ion battery candidate electrode materials. This result opens a new avenue for borides’ potential applications as electrode materials and fast ionic conductors. This work also portrays the map and landscape of ternary metal borides with similar chemical environments. With high efficiency, the prototype- and PXRD-assisted crystal structure prediction workflow opens a new avenue for exploring various material compositional spaces across the periodic table.
Interzeolite Transformation through Cross-Nucleation: A Molecular Mechanism for Seed-Assisted Synthesis
Carlos Chu-Jon - ,
Eli Martinez - ,
Andressa A. Bertolazzo - ,
Suvo Banik - ,
Jeffrey D. Rimer - ,
Subramanian K. R. S. Sankaranarayanan - , and
Valeria Molinero *
Polymorph selection and efficient crystallization are central goals in zeolite synthesis. Crystalline seeds are used for both purposes. While it has been proposed that zeolite seeds induce interzeolite transformation by dissolving into structural units that promote nucleation of the daughter crystal, the seed’s structural elements do not always match those of the target zeolite. This discrepancy raises the question of how the seed promotes the daughter phase. Here, we present the first molecularly resolved investigation of seed-assisted zeolite synthesis. Using molecular simulations, we reproduce the experimental finding that a parent zeolite can promote the nucleation of a daughter zeolite even when it lacks common composite building units (CBUs) or crystal planes. Modeling the seed-assisted synthesis of an AFI-type zeolite using zeolite CHA, our simulations indicate that stand-alone CBUs from the parent seed do not facilitate daughter crystal formation. However, introducing the intact seed significantly reduces the synthesis time, supporting that seed integrity is key to increased efficiency. This reduction arises from the cross-nucleation of the AFI-type zeolite on the CHA (001) face. We find that parent and daughter zeolites are connected by an interfacial transition layer with an order distinct from that of both zeolites. Simulations reveal that cross-nucleation occurs over a broad range of synthesis conditions. We argue that cross-nucleation would be most favorable for zeolite pairs that share crystalline planes such as those forming intergrowths. Our findings suggest that the prevalence of intergrowths with a common lattice plane in zeolite synthesis is likely a kinetic effect of accelerated cross-nucleation.
Smallest [5,6]Fullerene as Building Blocks for 2D Networks with Superior Stability and Enhanced Photocatalytic Performance
Jiaqi Wu - and
Bo Peng *
This publication is Open Access under the license indicated. Learn More
The assembly of molecules to form covalent networks can create varied lattice structures with physical and chemical properties distinct from those of conventional atomic lattices. Using the smallest stable [5,6]fullerene units as building blocks, various 2D C24 networks can be formed with superior stability and strength compared to the recently synthesized monolayer polymeric C60. Monolayer C24 harnesses the properties of both carbon crystals and fullerene molecules, such as stable chemical bonds, suitable band gaps, and large surface area, facilitating photocatalytic water splitting. The electronic band gaps of C24 are comparable to those of TiO2, providing appropriate band edges with sufficient external potential for overall water splitting over the acidic and neutral pH range. Upon photoexcitation, strong solar absorption enabled by strongly bound bright excitons can generate carriers effectively, while the type-II band alignment between C24 and other 2D monolayers can separate electrons and holes in individual layers simultaneously. Additionally, the number of surface-active sites of C24 monolayers are three times more than that of their C60 counterparts in a much wider pH range, providing spontaneous reaction pathways for the hydrogen evolution reaction. Our work provides insights into materials design using tunable building blocks of fullerene units with tailored functions for energy generation, conversion, and storage.
Lewis-Acid Mediated Reactivity in Single-Molecule Junctions
Jazmine Prana - ,
Leopold Kim - ,
Thomas M. Czyszczon-Burton - ,
Grace Homann - ,
Sully F. Chen - ,
Zelin Miao - ,
María Camarasa-Gómez - , and
Michael S. Inkpen *
This publication is Open Access under the license indicated. Learn More
While chemical reactions at a gold electrode can be monitored using molecular conductance and driven by extrinsic stimuli, the intrinsic properties of the nanostructured interface may perform important additional functions that are not yet well understood. Here we evaluate these properties in studies of single-molecule junctions formed from components comprising 4,4′-biphenyl backbones functionalized with 12 different sulfur-based linker groups. With some linkers, we find evidence for in situ S–C(sp3) bond breaking, and C(sp2)–C(sp3) bond forming, reactions consistent with the ex situ transformations expected for those groups in the presence of a Lewis acid. Notably, we also approach the limits of substituent influence on the conductance of physisorbed sulfur-linked junctions. As an illustrative example, we show that a tert-butylthio-functionalized precursor can form both chemisorbed (Au–S) junctions, consistent with heterolytic S–C(sp3) bond cleavage and generation of a stable tert-butyl carbocation, as well as physisorbed junctions that are >1 order of magnitude lower conductance than analogous junctions comprising cyclic “locked” thioether contacts. These findings are supported by a systematic analysis of model thioether components comprising different simple hydrocarbon substituents of intermediate size, which do not form chemisorbed contacts and further clarify the inverse relationship between conductance and substituent steric bulk. First-principles calculations confirm that bulky sulfur-substituents increase the probability of forming junction geometries with reduced electronic coupling between the electrode and π-conjugated molecular backbone. Together, this work helps to rationalize the dual roles that linker chemical structure and metal electrode Lewis character can play in mediating interfacial reactions in break-junction experiments.
November 18, 2024
Poly(Ionic Liquid) Electrolytes at an Extreme Salt Concentration for Solid-State Batteries
Shinji Kondou *- ,
Mohanad Abdullah - ,
Ivan Popov - ,
Murillo L. Martins - ,
Luke A. O’Dell - ,
Hiroyuki Ueda - ,
Faezeh Makhlooghiazad - ,
Azusa Nakanishi - ,
Taku Sudoh - ,
Kazuhide Ueno - ,
Masayoshi Watanabe - ,
Patrick Howlett - ,
Heng Zhang - ,
Michel Armand - ,
Alexei P. Sokolov - ,
Maria Forsyth *- , and
Fangfang Chen *
Polymer-in-salt electrolytes were introduced three decades ago as an innovative solution to the challenge of low Li-ion conductivity in solvent-free solid polymer electrolytes. Despite significant progress, the approach still faces considerable challenges, ranging from a fundamental understanding to the development of suitable polymers and salts. A critical issue is maintaining both the stability and high conductivity of molten salts within a polymer matrix, which has constrained their further exploration. This research offers a promising solution by integrating cationic poly(ionic liquids) (polyIL) with a crystallization-resistive salt consisting of asymmetric anions. A stable polymer-in-salt electrolyte with an exceptionally high Li-salt content of up to 90 mol % was achieved, providing a valuable opportunity for the in-depth understanding of these electrolytes at an extremely high salt concentration. This work explicates how increased salt concentration affects coordination structures, glass transitions, ionic conductivity, and the decoupling and coupling of ion transport from structural dynamics in a polymer electrolyte, ultimately enhancing electrolyte performance. These findings provide significant knowledge advancement in the field, guiding the future design of polymer-in-salt electrolytes.
November 15, 2024
Heterogenous Chemistry of I2O3 as a Critical Step in Iodine Cycling
An Ning - ,
Jing Li - ,
Lin Du - ,
Xiaohua Yang - ,
Jiarong Liu - ,
Zhi Yang - ,
Jie Zhong - ,
Alfonso Saiz-Lopez - ,
Ling Liu *- ,
Joseph S. Francisco *- , and
Xiuhui Zhang *
Global iodine emissions have been increasing rapidly in recent decades, further influencing the Earth’s climate and human health. However, our incomplete understanding of the iodine chemical cycle, especially the fate of higher iodine oxides, introduces substantial uncertainties into atmospheric modeling. I2O3 was previously deemed a “dead end” in iodine chemistry; however, we provide atomic-level evidence that I2O3 can undergo rapid air–water or air–ice interfacial reactions within several picoseconds; these reactions are facilitated by prevalent chemicals on seawater such as amines and halide ions, to produce photolabile reactive iodine species such as HOI and IX (X = I, Br, and Cl). The heterogeneous chemistry of I2O3 leads to the rapid formation of iodate ions (IO3–), which is the predominant soluble iodine and its concentration cannot be well explained by current chemistry. These new loss pathways for atmospheric I2O3 can further explain its absence in field observations and its presence in laboratory experiments; furthermore, these pathways represent a heterogeneous recycling mechanism that can activate the release of reactive iodine from oceans, polar ice/snowpack, or aerosols. Rapid reactive adsorption of I2O3 can also promote the growth of marine aerosols. These findings provide novel insights into iodine geochemical cycling.
November 14, 2024
Preprocessed Monomer Interfacial Polymerization for Scalable Fabrication of High-Valent Cluster-Based Metal–Organic Framework Membranes
Yang Feng - ,
Zixi Kang *- ,
Zhikun Wang - ,
Zhanning Liu - ,
Q. Jason Niu - ,
Weidong Fan - ,
Lu Qiao - ,
Jia Pang - ,
Hu Chang - ,
Xiaolei Cui - ,
Lili Fan - ,
Hailing Guo - ,
Rongming Wang - ,
Dan Zhao *- , and
Daofeng Sun *
Current research on emergent membrane materials with ordered and stable nanoporous structures often overlooks the vital facet of manufacturing scalability. We propose the preprocessed monomer interfacial polymerization (PMIP) strategy for the scalable fabrication of high-valent cluster-based metal–organic framework (MOF) membranes with robust structures. Using a roll-to-roll device on commercial polymer supports, Zr-fum-MOF membranes are continuously processed at room temperature through the PMIP approach. These large-area membranes demonstrate the preeminent hydrogen separation capabilities, boasting an order of magnitude of permeance and a thrice-enhanced selectivity when juxtaposed with conventional polymeric membranes. The obtained PMIP-Zr-fum-MOF membranes possess superior stability in water compared with interfacial polymerization (IP)-processed low-valent metal-ion-based ZIF-8 membranes. Moreover, we have implemented the PMIP strategy’s universality to process the other four diverse MOF membranes. The proposal of PMIP significantly advances the scalable fabrication of water-stable high-valent cluster MOF membranes.
November 12, 2024
A Smart Polycage Membrane with Responsive Osmotic Energy Conversion Based on Synchronously Switchable Microporosity and Chargeability
Weibin Lin - ,
Li Cao - ,
Xin Liu - ,
Lukman O. Alimi - ,
Jinrong Wang - ,
Basem A. Moosa - ,
Zhiping Lai *- , and
Niveen M. Khashab *
Membranes with specific pore sizes are widely used in molecular separation, ion transport, and energy conversion. However, the molecular understanding of structure–property performance in membrane science has been an urgent and long-standing problem. A promising but challenging solution lies in the fine-tuning of the membrane microstructure and properties to control membrane performance. Here, we designed an exofunctionalized triskelion cage to construct smart polycage membranes with concurrently responsive pore apertures and charge property. The synthetic polyaza cage is decorated with exoextended aldehyde groups for membrane fabrication and multiple amine sites for postmodification. The engineered polycage membranes thereby are endowed with pH-responsive porosity and chargeability, which serve as excellent candidates to explore the influence of the pore size and charge properties on membrane performance. In this regard, we successfully demonstrated the responsive osmotic energy conversion of the polycage membrane with a power density increase of over fourfold. This result indicates that the chargeability here outcompetes microporosity in energy conversion performance, which is further supported by molecular simulations. Therefore, this smart polycage membrane not only offers a feasible strategy to regulate the membrane microstructure and charge property reversibly but also balances pore size and chargeability to control the membrane performance at the molecular level.
November 11, 2024
Recycling Sulfur-Poisoned Pd Catalysts via Thermal Atomization for Semi-Hydrogenation of Acetylene
Qiheng Li - ,
Shoujie Liu - ,
Jin-Cheng Liu *- ,
Zhi Li *- , and
Yadong Li *
Palladium catalysts are highly efficient for a variety of chemical industrial processes but are prone to being affected by poisons during practical application. Sulfur is one of the major poisons in Pd-based catalysts. The recycling of deeply poisoned Pd species like Pd sulfides is challenging due to the strong Pd–S bond. Herein, we proposed a top-down strategy to degrade Pd sulfides and create Pd single-atom sites simultaneously by one-step thermal atomization. Pd4S model nanoparticles were successfully converted to Pd single-atom sites supported on nitrogen and sulfur-codoped carbon (Pd1/N, S–C) after loading them on ZIF-8 and thermal treatment. PdZn intermediates were formed during the atomization process. Density functional theory revealed that the formation of PdZn helped the generation of vacancies adjacent to metal nanoparticles, which prompted the atomization process. This strategy can be facilely applied to the atomization of sulfur-poisoned commercial Pd/C, which shows the potential for recycling commercial catalysts. The optimal Pd1/N, S–C catalyst showed good activity and much enhanced selectivity than Pd4S for the semi-hydrogenation of acetylene.
November 9, 2024
Conformational Control of σ-Interference Effects in the Conductance of Permethylated Oligosilanes
Haoyang Pan - ,
Yangyu Dong - ,
Yudi Wang - ,
Jie Li - ,
Yajie Zhang *- ,
Song Gao - ,
Yongfeng Wang *- , and
Shimin Hou *
As silicon-based integrated circuits continue to shrink, their molecular characteristics become more pronounced. However, the structure–property relationship of silicon-based molecular junctions remains to be elucidated. Here, an intuitive explanation of the effects of backbone dihedral angles on transport properties in permethylated oligosilanes is presented employing the Ladder C model Hamiltonian combined with nonequilibrium Green’s function formalism. Backbone dihedral angles modulate quantum interference (QI), resulting in the change of the transmission coefficient at the Fermi energy (EF) by up to 6 orders of magnitude in Si4Me10. Because the types of QI (constructive or destructive) between molecular conductance orbitals (MCOs) are unchanged, the relative magnitudes of contributions from QI are critical. This quantitative aspect of QI is often neglected in previous theoretical studies. Small backbone dihedral angles lead to localized MCOs near EF and delocalized MCOs further away from EF. As a result, the constructive QI between the MCOs near EF is suppressed, while the destructive QI between other MCOs is enhanced. This insight opens an avenue to harness QI to realize ultrainsulating molecular devices.
November 7, 2024
Significant Chiral Asymmetry Observed in Neutral Amino Acid Ultraviolet Photolysis
Brendan Moore - ,
Linshan Zeng - ,
Pavle Djuricanin - ,
Ilsa R. Cooke - ,
Kirk W. Madison - , and
Takamasa Momose *
The origin of homochirality in biological organisms remains an open question. Some suggest that its origin might be extraterrestrial, specifically due to the exposure of chiral molecules to circularly polarized photons in interstellar space, which could cause an initial population imbalance leading to the homochirality observed today. However, this extraterrestrial hypothesis has not been widely accepted, largely due to the belief that molecular optical rotatory dispersion is too insignificant to create the substantial imbalance required for homochirality. Here we report experimental evidence that specific conformers of neutral amino acids exhibit significant asymmetry in the chiral destroying dissociation rate induced by circularly polarized photons. The observed anisotropy factor for the lowest energy conformer of leucine was remarkably large, reaching 0.1─a factor of 13 times larger than observed for zwitterionic leucine in solid films, and nearly 40 times greater than the anisotropy reported in the electronic absorption spectrum of gas-phase leucine ensembles at room temperature. This significant finding indicates that even if reported anisotropy values in the electronic absorption spectrum are low, the dissociation asymmetry of certain conformers can still be substantial. An anisotropy factor of 0.1 could result in an initial enantiomeric excess exceeding 10%, even with a 90% extent of reaction. This discovery suggests that asymmetric photodissociation of amino acids may have been a crucial factor in the emergence of biological homochirality.
DNA Nanopatch-Specific Modification of Probiotics for Ultrasound-Triggered Inflammatory Bowel Disease Therapy
Xiangbowen Jin - ,
Hongyang Li - ,
Sheng Pan - ,
Bin Song - ,
Yanping Jiang - ,
Haoliang Shi - ,
Jiawei Zhang - ,
Binbin Chu *- ,
Houyu Wang *- , and
Yao He *
Probiotics offer promising results for treating inflammatory bowel disease, yet precision therapy remains challenging, particularly in manipulating probiotics spatially and temporally and shielding them from oxidative stress. To address these limitations, herein we synthesized bacteria-specific DNA nanopatches to modify ultrasound-triggered engineered Escherichia coli Nissle 1917. These probiotics produced the anti-inflammatory cytokine interleukin-10 when stimulated by ultrasound and were fortified with DNPs for oxidative stress resistance. The DNPs were composed of rectangular DNA origami nanosheets with reactive oxygen species’ scavenging ability and bacterial targeting ligands of maltodextrin molecules. We systematically demonstrated that the DNPs could selectively attach to bacterial surface but not mammalian cell surface via the maltodextrin transporter pathway. To further enhance the bioavailability of engineered probiotics in the gastrointestinal tract, we employed a self-assembly strategy to encapsulate them using chitosan and sodium alginate. In a murine model of ulcerative colitis, this system significantly improved the gut barrier integrity and reduced inflammation. Our results indicate that this DNA nanopatch-bacteria system holds substantial promise for mitigating oxidative stress, correcting microbiota dysbiosis, and enhancing the intestinal barrier function in colitis.
November 5, 2024
Activating the Mn Single Atomic Center for an Efficient Actual Active Site of the Oxygen Reduction Reaction by Spin-State Regulation
Kiwon Kim - ,
Gyuchan Kim - ,
Taeyoung Jeong - ,
Wonyoung Lee - ,
Yunho Yang - ,
Byung-Hyun Kim - ,
Bubryur Kim - ,
Byeongyong Lee - ,
Joonhee Kang *- , and
Myeongjin Kim *
The ligand engineering for single-atom catalysts (SACs) is considered a cutting-edge strategy to tailor their electrocatalytic activity. However, the fundamental reasons underlying the reaction mechanism and the contemplation for which the actual active site for the catalytic reaction depends on the pyrrolic and pyridinic N ligand structure remain to be fully understood. Herein, we first reveal the relationship between the oxygen reduction reaction (ORR) activity and the N ligand structure for the manganese (Mn) single atomic site by the precisely regulated pyrrolic and pyridinic N4 coordination environment. Experimental and theoretical analyses reveal that the long Mn–N distance in Mn–pyrrolic N4 enables a high spin state of the Mn center, which is beneficial to reduce the adsorption strength of oxygen intermediates by the high filling state in antibond orbitals, thereby activating the Mn single atomic site to achieve a half-wave potential of 0.896 V vs RHE with outstanding stability in acidic media. This work provides a new fundamental insight into understanding the ORR catalytic origin of Mn SACs and the rational design strategy of SACs for various electrocatalytic reactions.
Site-Specific Histidine Aza-Michael Addition in Proteins Enabled by a Ferritin-Based Metalloenzyme
Jo-Chu Tsou - ,
Chun-Ju Tsou - ,
Chun-Hsiung Wang - ,
An-Li A. Ko - ,
Yi-Hui Wang - ,
Huan-Hsuan Liang - ,
Jia-Cheng Sun - ,
Kai-Fa Huang - ,
Tzu-Ping Ko - ,
Shu-Yu Lin - , and
Yane-Shih Wang *
This publication is Open Access under the license indicated. Learn More
Histidine modifications of proteins are broadly based on chemical methods triggering N-substitution reactions such as aza-Michael addition at histidine’s moderately nucleophilic imidazole side chain. While recent studies have demonstrated chemoselective, histidine-specific modifications by further exploiting imidazole’s electrophilic reactivity to overcome interference from the more nucleophilic lysine and cysteine, achieving site-specific histidine modifications remains a major challenge due to the absence of spatial control over chemical processes. Herein, through X-ray crystallography and cryo-electron microscopy structural studies, we describe the rational design of a nature-inspired, noncanonical amino-acid-incorporated, human ferritin-based metalloenzyme that is capable of introducing site-specific post-translational modifications (PTMs) to histidine in peptides and proteins. Specifically, chemoenzymatic aza-Michael additions on single histidine residues were carried out on eight protein substrates ranging from 10 to 607 amino acids including the insulin peptide hormone. By introducing an insulin-targeting peptide into our metalloenzyme, we further directed modifications to be carried out site-specifically on insulin’s B-chain histidine 5. The success of this biocatalysis platform outlines a novel approach in introducing residue- and, moreover, site-specific post-translational modifications to peptides and proteins, which may further enable reactions to be carried out in vivo.
November 4, 2024
Electric Field-Induced Sequential Prototropic Tautomerism in Enzyme-like Nanopocket Created by Single Molecular Break Junction
PA Sreelakshmi - ,
Rahul Mahashaya - ,
Susanne Leitherer *- ,
Umar Rashid - ,
Joseph M. Hamill - ,
Manivarna Nair - ,
Pachaiyappan Rajamalli *- , and
Veerabhadrarao Kaliginedi *
This publication is Open Access under the license indicated. Learn More
Mastering the control of external stimuli-induced chemical transformations with detailed insights into the mechanistic pathway is the key for developing efficient synthetic strategies and designing functional molecular systems. Enzymes, the most potent biological catalysts, efficiently utilize their built-in electric field to catalyze and control complex chemical reactions within the active site. Herein, we have demonstrated the interfacial electric field-induced prototropic tautomerization reaction in acylhydrazone entities by creating an enzymatic-like nanopocket within the atomically sharp gold electrodes using a mechanically controlled break junction (MCBJ) technique. In addition to that, the molecular system used here contains two coupled acylhydrazone reaction centers, hence demonstrating a cooperative stepwise electric field-induced reaction realized at the single molecular level. Furthermore, the mechanistic studies revealed a proton relay-assisted tautomerization showing the importance of external factors such as solvent in such electric field-driven reactions. Finally, single-molecule charge transport and energetics calculations of different molecular species at various applied electric fields using a polarizable continuum solvent model confirm and support our experimental findings. Thus, this study demonstrates that mimicking an enzymatic pocket using a single molecular junction’s interfacial electric field as a trigger for chemical reactions can open new avenues to the field of synthetic chemistry.
November 2, 2024
Rethinking Assumptions: Assessing the Impact of Strong Magnetic Fields on Luminescence Thermometry
Maxime Aragon-Alberti - ,
Mateusz Dyksik - ,
Carlos D. S. Brites - ,
Jérôme Rouquette - ,
Paulina Plochocka *- ,
Luís D. Carlos *- , and
Jérôme Long *
Luminescence (nano)thermometry has exploded in popularity, offering a remote detection way to measure temperature across diverse fields like nanomedicine, microelectronics, catalysis, and plasmonics. A key advantage is its supposed immunity to strong electromagnetic fields, a crucial feature in many environments. However, this assumption lacks comprehensive experimental verification as most of the proposed luminescent thermometers rely on magnetic ions, such as lanthanides. Here, we address this gap by critically examining the thermometric response of the luminescent molecular thermometer [Tb0.93Eu0.07(bpy)2(NO3)3] (bpy = 2,2′-bipyridine) under high magnetic fields (up to 58 T). Our findings reveal that the conventional intensity-based method for Tb/Eu luminescent thermometers fails even under weak magnetic fields. However, careful data analysis identified specific transitions with minimal magnetic correlation, enabling the thermometer to operate across the entire temperature range up to 20 T, and with larger fields for temperatures exceeding 120 K. This study highlights the strong dependence of thermometric performance on material properties, urging caution, but also offers a path forward for developing robust luminescent thermometers in such environments.
October 31, 2024
Electrochemically Determined and Structurally Justified Thermochemistry of H atom Transfer on Ti-Oxo Nodes of the Colloidal Metal–Organic Framework Ti-MIL-125
Nazmiye Gökçe Altınçekiç - ,
Chance W. Lander - ,
Ayman Roslend - ,
Jiaqi Yu - ,
Yihan Shao - , and
Hyunho Noh *
Titanium dioxide (TiO2) has long been employed as a (photo)electrode for reactions relevant to energy storage and renewable energy synthesis. Proton-coupled electron transfer (PCET) reactions with equimolar amounts of protons and electrons at the TiO2 surface or within the bulk structure lie at the center of these reactions. Because a proton and an electron are thermochemically equivalent to an H atom, these reactions are essentially H atom transfer reactions. Thermodynamics of H atom transfer has a complex dependence on the synthetic protocol and chemical history of the electrode, the reaction medium, and many others; together, these complications preclude the understanding of the H atom transfer thermochemistry with atomic-level structural knowledge. Herein, we report our success in employing open-circuit potential (EOCP) measurements to quantitatively determine the H atom transfer thermochemistry at structurally well-defined Ti-oxo clusters within a colloidally stabilized metal–organic framework (MOF), Ti-MIL-125. The free energy to transfer H atom, Ti3+O–H bond dissociation free energy (BDFE), was measured to be 68(2) kcal mol–1. To the best of our understanding, this is the first report on using EOCP measurements to quantify thermochemistry on any MOFs. The proton topology, the structural change upon the redox reaction, and BDFE values were further quantitatively corroborated using computational simulations. Furthermore, comparisons of the EOCP-derived BDFEs of Ti-MIL-125 to similar parameters in the literature suggest that EOCP should be the preferred method for quantitatively accurate BDFE calculations. The reported success in employing EOCP for nanosized Ti-MIL-125 should lay the ground for thermochemical measurements of other colloidal systems, which are otherwise challenging. Implications of these measurements on Ti-MIL-125 as an H atom acceptor in chemical reactions and comparisons with other MOFs/metal oxides are discussed.
October 30, 2024
High Entropy 2D Layered Double Hydroxide Nanosheet Toward Cascaded Nanozyme-Initiated Chemodynamic and Immune Synergistic Therapy
Chen Wang - ,
Fengying Yuan - ,
Zichao Yan - ,
Tianqi Zhang - ,
Chenchen Fu - ,
Ya Li - ,
Guidong Dai - ,
Hyeong Seok Kim - ,
Shuwei Xia - ,
Liangmin Yu - ,
Snehasish Debnath - ,
Wen Xiu Ren *- ,
Jian Shu *- ,
Meng Qiu *- , and
Jong Seung Kim *
High-entropy nanomaterials (HEMs) are a hot topic in the fields of energy and catalysis. However, in terms of promising biomedical applications, potential therapeutic studies involving HEMs are unprecedented. Herein, we demonstrated high entropy two-dimensional layered double hydroxide (HE-LDH) nanoplatforms with versatile physicochemical advantages that reprogram the tumor microenvironment (TME) and provide antitumor treatment via cascaded nanoenzyme-initiated chemodynamic and immune synergistic therapy. In response to the TME, the multifunctional HE-LDHs sequentially release metal ions, such as Co2+, Fe3+, and Cu2+, exhibiting exquisite superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPX) activities. The multiple enzymatic activities convert specific tumor metabolites into a continuous supply of cytotoxic reactive oxygen species (ROS) to relieve hypoxia under a TME. Thus, HE-LDHs facilitate robust nanozyme-initiated chemodynamic therapy (NCDT), achieving high therapeutic efficacy without obvious side effects. In addition, the release of Zn2+ from the HE-LDH matrix triggers the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling pathway, boosting the innate immunotherapeutic efficacy. The intratumoral applications of the nanocomposite in tumor-bearing mice models indicate that HE-LDH-mediated NCDT and immune synergistic therapy effectively upregulated the expression of relevant antitumor cytokines and induced cytotoxic T lymphocyte infiltration, showing superior efficacy in inhibiting tumor growth. Therefore, this work opens a new research direction toward synchronized NCDT and immunotherapy of tumors using HEMs for advanced healthcare.
To Investigate Electron Transfer Properties on Silicalite-1 Zeolite for Potential Electrocatalytic Applications
Yingying Jin - ,
Xichen Yin - ,
Guanghua Yu - ,
Qiming Sun *- , and
Jiong Wang *
To develop high-performance electrocatalysts is critical to sustainable conversion and storage of renewable energy. Silicalite-1 (S-1) zeolite is considered promising for constructing electrocatalysts featuring uniform and precise porosity and a stable structural skeleton even at extreme potentials. However, its electrochemical properties remain poorly understood, particularly regarding the roles of internal pore channels. Herein, inner- and outer-sphere electron transfer (ISET/OSET) routes on the S-1 zeolite were investigated by classical redox probes. The results for the first time revealed that the ISET kinetics inside the pores of S-1 zeolite is more rapid than that on external surfaces, optimized by microporous scale channels and terminated hydroxyl groups. Conversely, the kinetics of the OSET did not closely depend on the porosity and surface properties of the S-1 zeolite. These electrochemical insights further initiated a lithium-ion-incorporated S-1 zeolite with rapid ISET kinetics for electrocatalysis of oxygen reduction. It demonstrated a high performance of 85% selectivity for H2O2 production in a neutral solution and a yield of 9.2 mol gcat–1 h–1 when configured in a flow cell.
October 29, 2024
Polyalkenamers as Drop-In Additives for Ring-Opening Metathesis Polymerization: A Promising Upcycling Paradigm
Jeffrey C. Foster *- ,
Joshua T. Damron - ,
Jackie Zheng - ,
Chao Guan - ,
Ilja Popovs - ,
Md. Anisur Rahman - ,
Nicholas J. Galan - ,
Isaiah T. Dishner - , and
Tomonori Saito
We report a distinct strategy to upcycle waste polyalkenamers such as polybutadiene into new, performance-advantaged materials by using them as drop-in additives for ring-opening metathesis polymerization (ROMP). The polyalkenamers serve as competent chain-transfer agents in ROMPs of common classes of cyclic olefin monomers, facilitating good molecular weight control, allowing low Ru catalyst loadings, and enabling efficient incorporation of the polyalkenamer into the synthesized polymeric material. We successfully demonstrate ROMP using model polyalkenamers and translate these learnings to leverage commercial polybutadiene and acrylonitrile butadiene styrene (ABS) as chain transfer agents for ROMP copolymerizations. Critically, our strategy is shown to be highly efficient and operationally simple, quantitatively incorporating the polyalkenamer and inheriting aspects of its thermomechanical performance. Our results highlight a promising pathway for the upcycling of polyalkenamers and provide an alternative to existing deconstruction and functional upcycling strategies.
October 28, 2024
Unlocking Superior Hydrogen Oxidation and CO Poisoning Resistance on Pt Enabled by Tungsten Nitride-Mediated Electronic Modulation
Bin Cai - ,
Di Shen - ,
Ying Xie - ,
Haijing Yan - ,
Yucheng Wang *- ,
Xiaodong Chen *- ,
Lei Wang *- , and
Honggang Fu *
Enhancing the activity and CO poisoning resistance of Pt-based catalysts for the anodic hydrogen oxidation reaction (HOR) poses a significant challenge in the development of proton exchange membrane fuel cells. Herein, we leverage theoretical calculations to demonstrate that tungsten nitride (WN) can intricately modulate the electronic structure of Pt. This modulation optimizes the hydrogen adsorption, significantly boosting HOR activity, and simultaneously weakens the CO adsorption, markedly improving resistance to CO poisoning. Through prescreening with rational design, we synthesized an efficient catalyst comprising a minimal Pt content (only 1.4 wt %) supported on the small-sized WN/reduced graphite oxide (Pt@WN/rGO). As anticipated, this catalyst showcases a remarkable acidic HOR mass activity of 3060 A gPt–1, which is approximately 11.8 times greater than that of the commercial 20 wt % Pt/C catalyst. Impressively, it maintains high activity with 98.2% retention even in the presence of 1000 ppm of CO, indicating exceptional poison resistance. Operando synchrotron radiation analyses reveal that WN harmonizes the electron state of Pt during electrochemical reactions, optimizing hydrogen adsorption/desorption dynamics. This leads to a lower peak potential of CO stripping on Pt@WN/rGO compared to that on Pt/rGO, suggesting that WN mitigates competitive CO adsorption and enhances the availability of hydrogen adsorption sites on Pt. The synergistic effect significantly accelerates HOR activity and increases antipoisoning efficacy. The assembled PEMFC demonstrates substantial tolerance to CO concentration from 10 to 1000 ppm in the H2/CO mixture.
October 27, 2024
Machine Learning Accelerated Discovery of Entropy-Stabilized Oxide Catalysts for Catalytic Oxidation
Xiaolan Duan - ,
Yang Li - ,
Jiahua Zhao - ,
Mengyuan Zhang - ,
Xiaopeng Wang - ,
Li Zhang - ,
Xiaoxuan Ma - ,
Ying Qu - , and
Pengfei Zhang *
The catalytic properties of unary to ternary metal oxides were already well experimentally explored, and the left space seems like only high entropy metal oxides (HEOs, element types ≥5). However, the countless element compositions make the trial-and-error method of discovering HEO catalysts impossible. Herein, based on the study of the crystal phase and catalytic performance of the ACr2Ox catalyst system, the strong correlation between the single spinel phase and good catalytic activity of CH4 oxidation was inferred owing to the similar element importance sequences, which were acquired by the corresponding high accuracy machine learning models (cross-validation score >0.7). Furthermore, searching for negative data and choosing the proper training data resulted in high-quality regression models to search for better catalysts. Finally, the screened irregular catalyst Ni0.04Co0.48Zn0.36V0.12Cr2Ox with outstanding sulfur and moisture resistance and long-term stability (>7000 h, T90 = 345 °C) envisions the potential of applying the machine learning method to discover HEOs for target processes.
October 25, 2024
Interpretable Learning of Accelerated Aging in Lithium Metal Batteries
Xinyan Liu - ,
Bo-Bo Zou - ,
Ya-Nan Wang - ,
Xiang Chen - ,
Jia-Qi Huang - ,
Xue-Qiang Zhang *- ,
Qiang Zhang *- , and
Hong-Jie Peng *
Lithium metal batteries (LMBs) with high energy density are perceived as the most promising candidates to enable long-endurance electrified transportation. However, rapid capacity decay and safety hazards have impeded the practical application of LMBs, where the entangled complex degradation pattern remains a major challenge for efficient battery design and engineering. Here, we present an interpretable framework to learn the accelerated aging of LMBs with a comprehensive data space containing 79 cells varying considerably in battery chemistries and cell parameters. Leveraging only data from the first 10 cycles, this framework accurately predicts the knee points where aging starts to accelerate. Leaning on the framework’s interpretability, we further elucidate the critical role of the last 10%-depth discharging on LMB aging rate and propose a universal descriptor based solely on early cycle electrochemical data for rapid evaluation of electrolytes. The machine learning insights also motivate the design of a dual-cutoff discharge protocol, which effectively extends the cycle life of LMBs by a factor of up to 2.8.
October 24, 2024
Directional Transport in Hierarchically Aligned ZSM-5 Zeolites with High Catalytic Activity
Bojun Zeng - ,
Siming Wu *- ,
Mingbin Gao - ,
Ge Tian *- ,
Liying Wang - ,
Zhiwen Yin - ,
Zhiyi Hu - ,
Wen Zhang - ,
Ganggang Chang - ,
Mao Ye - ,
Christoph Janiak - ,
Osamu Terasaki - , and
Xiaoyu Yang *
Zeolites, the most technically important crystalline microporous materials, are indispensable cornerstones of chemical engineering because of their remarkable catalytic properties and adsorption capabilities. Numerous studies have demonstrated that the hierarchical engineering of zeolites can maximize accessible active sites and improve mass transport, which significantly decreases the internal diffusion limits to achieve the desired performance. However, the construction of hierarchical zeolites with ordered alignments and size-controlled substructures in a convenient way is highly challenging. Herein, we develop a facile procedure using two common structure-directing agents, tetrapropylammonium hydroxide (TPAOH) and tetraethylammonium hydroxide (TEAOH), to synthesize hierarchically aligned ZSM-5 (Hie-ZSM-5) crystals with a-axis alignment substructures of controllable size. The control of the substructure size (α) in the range of 10–60 nm and the corresponding similarity (r = α/β, where β is the size of Hie-ZSM-5) ranging from 0.004 to 0.033 can be tuned by varying the Si/Al ratios (40–120). A systematic investigation of the overall crystallization process, using time-dependent XRD, SEM, TEM, and solid-state magic-angle spinning NMR (13C, 27Al, 29Si) methods, enable us to construct a solid mechanism for the generation of Hie-ZSM-5. Most importantly, directional transport in the unique structures of Hie-ZSM-5 efficiently enhances mass diffusion, as well as catalytic activity and stability. These findings improve our understanding of the zeolite crystallization process and inspire novel methods for the rational design of hierarchical zeolites.
October 23, 2024
Unraveling the Oxygen Vacancy–Performance Relationship in Perovskite Oxides at Atomic Precision via Precise Synthesis
Xiyang Wang - ,
Qinghua Zhang - ,
Xinbo Li - ,
Fanqi Meng - ,
Shengru Chen - ,
Zuolong Chen - ,
Yingge Cong - ,
Teak Boyko - ,
Tom Regier - ,
Er-jia Guo *- ,
Yi Xiao - ,
Liping Li - ,
Guangshe Li - ,
Shouhua Feng *- , and
Yimin A. Wu *
Understanding the fundamental effect of the oxygen vacancy atomic structure in perovskite oxides on catalytic properties remains challenging due to diverse facets, surface sites, defects, etc. in traditional powder catalysts and the inherent structural complexity. Through quantitative synthesis of tetrahedral (LaCoO2.5-T), pyramidal (LaCoO2.5-P), and octahedral (LaCoO3) epitaxial thin films as model catalysts, we demonstrate the reactivity orders of active-site geometrical configurations in oxygen-deficient perovskites during the CO oxidation model reaction: CoO4 tetrahedron > CoO6 octahedron > CoO5 pyramid. Ambient-pressure Co L-edge and O K-edge XAS spectra clarify the dynamic evolutions of active-site electronic structures during realistic catalytic processes and highlight the important roles of defect geometrical structures. In addition, in situ XAS and resonant inelastic X-ray scattering spectra and density functional theory calculations directly reveal the nature of high reactivity for CoO4 sites and that the derived shallow-acceptor defect levels in the band structure facilitate the adsorption and activation of reactive gases, resulting in more than 23-fold enhancement for catalytic reaction rates than CoO5 sites.
October 8, 2024
Regulating Local Coordination Sphere of Ir Single Atoms at the Atomic Interface for Efficient Oxygen Evolution Reaction
Ashwani Kumar - ,
Marcos Gil-Sepulcre - ,
Jean Pascal Fandré - ,
Olaf Rüdiger - ,
Min Gyu Kim - ,
Serena DeBeer - , and
Harun Tüysüz *
This publication is Open Access under the license indicated. Learn More
Single-atom catalysts dispersed on an oxide support are essential for overcoming the sluggishness of the oxygen evolution reaction (OER). However, the durability of most metal single-atoms is compromised under harsh OER conditions due to their low coordination (weak metal–support interactions) and excessive disruption of metal-Olattice bonds to enable lattice oxygen participation, leading to metal dissolution and hindering their practical applicability. Herein, we systematically regulate the local coordination of Irsingle-atoms at the atomic level to enhance the performance of the OER by precisely modulating their steric localization on the NiO surface. Compared to conventional Irsingle-atoms adsorbed on NiO surface, the atomic Ir atoms partially embedded within the NiO surface (Iremb-NiO) exhibit a 2-fold increase in Ir–Ni second-shell interaction revealed by X-ray absorption spectroscopy (XAS), suggesting stronger metal–support interactions. Remarkably, Iremb-NiO with tailored coordination sphere exhibits excellent alkaline OER mass activity and long-term durability (degradation rate: ∼1 mV/h), outperforming commercial IrO2 (∼26 mV/h) and conventional Irsingle-atoms on NiO (∼7 mV/h). Comprehensive operando X-ray absorption and Raman spectroscopies, along with pH-dependence activity tests, identified high-valence atomic Ir sites embedded on the NiOOH surface during the OER followed the lattice oxygen mechanism, thereby circumventing the traditional linear scaling relationships. Moreover, the enhanced Ir–Ni second-shell interaction in Iremb-NiO plays a crucial role in imparting structural rigidity to Ir single-atoms, thereby mitigating Ir-dissolution and ensuring superior OER kinetics alongside sustained durability.
September 20, 2024
Engineering Screw Dislocations in Covalent Organic Frameworks
Bhausaheb Dhokale - ,
Kira Coe-Sessions - ,
Michael J. Wenzel - ,
Alathea E. Davies - ,
Taylor Kelsey - ,
Jonathan A. Brant - ,
Laura de Sousa Oliveira - ,
Bruce A. Parkinson - , and
John O. Hoberg *
We report the application of a Pictet-Spengler reaction to the synthesis of covalent organic frameworks (COFs) using functionalized terephthalaldehydes. The COFs produced show an increased propensity to generate screw dislocations and produce multilayered flakes when compared with other 2D-COFs. Using HRTEM, definitive evidence for screw dislocations was obtained and is presented. The effects on separations using these materials in membranes are also reported.