
About the Cover:
A lipid-modified poly(guanidine thioctic acid) polymer is developed as a fortifier for lipid nanoparticles with the capability to eliminate reactive oxygen species, greatly improving the translation efficiency and alleviating inflammation of mRNA vaccines. This formulation shows promising potential in the fabrication of next-generation mRNA vaccines and therapeutics.
View the article.Perspectives

Promises and Perils of Big Data: Philosophical Constraints on Chemical Ontologies
Rebekah Duke - ,
Ryan McCoy - ,
Chad Risko *- , and
Julia R. S. Bursten *
Chemistry is experiencing a paradigm shift in the way it interacts with data. So-called “big data” are collected and used at unprecedented scales with the idea that algorithms can be designed to aid in chemical discovery. As data-enabled practices become ever more ubiquitous, chemists must consider the organization and curation of their data, especially as it is presented to both humans and increasingly intelligent algorithms. One of the most promising organizational schemes for big data is a construct termed an ontology. In data science, ontologies are systems that represent relations among objects and properties in a domain of discourse. As chemistry encounters larger and larger data sets, the ontologies that support chemical research will likewise increase in complexity, and the future of chemistry will be shaped by the choices made in developing big data chemical ontologies. How such ontologies will work should therefore be a subject of significant attention in the chemical community. Now is the time for chemists to ask questions about ontology design and use: How should chemical data be organized? What can be reasonably expected from an organizational structure? Is a universal ontology tenable? As some of these questions may be new to chemists, we recommend an interdisciplinary approach that draws on the long history of philosophers of science asking questions about the organization of scientific concepts, constructs, models, and theories. This Perspective presents insights from these long-standing studies and initiates new conversations between chemists and philosophers.
Communications

Efficient Screening of Pharmaceutical Cocrystals by Microspacing In-Air Sublimation
Huimin Li - ,
Lei Wang *- ,
Xin Ye - ,
Changlin Yao - ,
Shuhong Song - ,
Yaqian Qu - ,
Jinke Jiang - ,
Hongshuai Wang - ,
Peizhuo Han - ,
Yang Liu - , and
Xutang Tao *
Cocrystal screening and single-crystal growth remain the primary obstacles in the development of pharmaceutical cocrystals. Here, we present a new approach for cocrystal screening, microspacing in-air sublimation (MAS), to obtain new cocrystals and grow high-quality single crystals of cocrystals within tens of minutes. The method possesses the advantages of strong designable ability of devices, user-friendly control, and compatibility with materials, especially for the thermolabile molecules. A novel drug–drug cocrystal of favipiravir (FPV) with salicylamide (SAA) was first discovered by this method, which shows improved physiochemical properties. Furthermore, this method proved effective in cultivating single crystals of FPV–isonicotinamide (FPV-INIA), FPV–urea, FPV–nicotinamide (FPV-NIA), and FPV–tromethamine (FPV-Tro) cocrystals, and the structures of these cocrystals were determined for the first time. By adjusting the growth temperature and growth distance precisely, we also achieved single crystals of 10 different paracetamol (PCA) cocrystals and piracetam (PIR) cocrystals, which underscores the versatility and efficiency of this method in pharmaceutical cocrystal screening.

Photoredox Nucleophilic (Radio)fluorination of Alkoxyamines
Sebastiano Ortalli - ,
Joseph Ford - ,
Andrés A. Trabanco - ,
Matthew Tredwell - , and
Véronique Gouverneur *
This publication is Open Access under the license indicated. Learn More
Herein, we report a photoredox nucleophilic (radio)fluorination using TEMPO-derived alkoxyamines, a class of substrates accessible in a single step from a diversity of readily available carboxylic acids, halides, alkenes, alcohols, aldehydes, boron reagents, and C–H bonds. This mild and versatile one-electron pathway affords radiolabeled aliphatic fluorides that are typically inaccessible applying conventional nucleophilic substitution technologies due to insufficient reactivity and competitive elimination. Automation of this photoredox process is also demonstrated with a user-friendly and commercially available photoredox flow reactor and radiosynthetic platform, therefore expediting access to labeled aliphatic fluorides in high molar activity (Am) for (pre)clinical evaluation.

Cyclic Peptides from Graspetide Biosynthesis and Native Chemical Ligation
Brian Choi - ,
Arthur Acuña - , and
A. James Link *
The ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily of natural products includes many examples of cyclic peptides with diverse macrocyclization chemistries. The graspetides, one family of macrocyclized RiPPs, harbor side chain–side chain ester or amide linkages. We recently reported the structure and biosynthesis of the graspetide pre-fuscimiditide, a 22-amino-acid (aa) peptide with two ester cross-links forming a stem–loop structure. These cross-links are introduced by a single graspetide synthetase, the ATP-grasp enzyme ThfB. Here we show that ThfB can also catalyze the formation of amide or thioester cross-links in prefuscimiditide, with thioester formation being especially efficient. We further show that upon proteolysis to reveal an N-terminal cysteine residue, the thioester-linked peptide rapidly and quantitatively rearranges via native chemical ligation into an isopeptide-bonded head-to-tail cyclic peptide. The solution structure of this rearranged peptide was determined by using 2D NMR spectroscopy experiments. Our methodology offers a straightforward recombinant route to head-to-tail cyclic peptides.

Chemoselective Diazine Dearomatization: The Catalytic Enantioselective Dearomatization of Pyrazine
Devin R. Ketelboeter - ,
Mukesh Pappoppula - , and
Aaron Aponick *
Despite much progress in the area of dearomatization, the enantioselective dearomatization of heterocycles is limited to those with a single heteroatom. Here we report a highly enantioselective copper-catalyzed dearomatization of pyrazine, a diazine, leading to chiral C-substituted piperazines. When exposed to a chloroformate and an alkyne in the presence of a catalyst derived from a copper salt and the chiral ligand StackPhos, pyrazine is readily dearomatized to provide a 2,3-disubstituted dihydropyrazine as single diastereomer in high enantiomeric excess. Mechanistic studies support a noninnocent involvement of chloride ion preventing a second iminium alkynylation, thus enabling subsequent functionalization at the second reactive site. The synthetically useful dihydropyrazine products, obtained in up to 95% yield and 99% ee, can be further manipulated to form optically active C-substituted piperazines and C1-symmetric 1,2-diamines.

Manganese(III) Nitrate Complexes as Bench-Stable Powerful Oxidants
Ananya Saju - ,
Matthew R. Crawley - ,
Samantha N. MacMillan - , and
David C. Lacy *
We report herein a convenient one-pot synthesis for the shelf-stable molecular complex [Mn(NO3)3(OPPh3)2] (2) and describe the properties that make it a powerful and selective one-electron oxidation (deelectronation) reagent. 2 has a high reduction potential of 1.02 V versus ferrocene (MeCN) (1.65 vs normal hydrogen electrode), which is one the highest known among readily available redox agents used in chemical synthesis. 2 exhibits stability toward air in the solid state, can be handled with relative ease, and is soluble in most common laboratory solvents such as MeCN, dichloromethane, and fluorobenzene. 2 is substitutionally labile with respect to the coordinated (pseudo)halide ions enabling the synthesis of other new Mn(III) nitrato complexes also with high reduction potentials ranging from 0.6 to 1.0 V versus ferrocene.
Articles

Breaking a Molecular Scaling Relationship Using an Iron–Iron Fused Porphyrin Electrocatalyst for Oxygen Reduction
Daiki Nishiori - ,
Jan Paul Menzel - ,
Nicholas Armada - ,
Edgar A. Reyes Cruz - ,
Brent L. Nannenga - ,
Victor S. Batista - , and
Gary F. Moore *
The design of efficient electrocatalysts is limited by scaling relationships governing trade-offs between thermodynamic and kinetic performance metrics. This ″iron law″ of electrocatalysis arises from synthetic design strategies, where structural alterations to a catalyst must balance nucleophilic versus electrophilic character. Efforts to circumvent this fundamental impasse have focused on bioinspired applications of extended coordination spheres and charged sites proximal to a catalytic center. Herein, we report evidence for breaking a molecular scaling relationship involving electrocatalysis of the oxygen reduction reaction (ORR) by leveraging ligand design. We achieve this using a binuclear catalyst (a diiron porphyrin), featuring a macrocyclic ligand with extended electronic conjugation. This ligand motif delocalizes electrons across the molecular scaffold, improving the catalyst’s nucleophilic and electrophilic character. As a result, our binuclear catalyst exhibits low overpotential and high catalytic turnover frequency, breaking the traditional trade-off between these two metrics.

Rapid Enrichment of a Native Multipass Transmembrane Protein via Cell Membrane Electrophoresis through Buffer pH and Ionic Strength Adjustment
Tzu-Tzu Liu - ,
Sin-Han Huang - , and
Ling Chao *
This publication is Open Access under the license indicated. Learn More
Supported membrane electrophoresis is a promising technique for collecting membrane proteins in native bilayer environments. However, the slow mobility of typical transmembrane proteins has impeded the technique’s advancement. Here, we successfully applied cell membrane electrophoresis to rapidly enrich a 12-transmembrane helix protein, glucose transporter 1 with antibodies (GLUT1 complex), by tuning the buffer pH and ionic strength. The identified conditions allowed the separation of the GLUT1 complex and a lipid probe, Fast-DiO, within a native-like environment in a few minutes. A force model was developed to account for distinct electric and drag forces acting on the transmembrane and aqueous-exposed portion of a transmembrane protein as well as the electroosmotic force. This model not only elucidates the impact of size and charge properties of transmembrane proteins but also highlights the influence of pH and ionic strength on the driving forces and, consequently, electrophoretic mobility. Model predictions align well with experimentally measured electrophoretic mobilities of the GLUT1 complex and Fast-DiO at various pH and ionic strengths as well as with several lipid probes, lipid-anchored proteins, and reconstituted membrane proteins from previous studies. Force analyses revealed the substantial membrane drag of the GLUT1 complex, significantly slowing down electrophoretic mobility. Besides, the counterbalance of similar magnitudes of electroosmotic and electric forces results in a small net driving force and, consequently, reduced mobility under typical neutral pH conditions. Our results further highlight how the size and charge properties of transmembrane proteins influence the suitable range of operating conditions for effective movement, providing potential applications for concentrating and isolating membrane proteins within this platform.

General Installation of (4H)-Imidazolone cis-Amide Bioisosteres Along the Peptide Backbone
Brendan J. Wall - ,
Krishna K. Sharma - ,
Emily A. O’Brien - ,
Aaron Donovan - , and
Brett VanVeller *
Imidazolones represent an important class of heterocycles present in a wide range of pharmaceuticals, metabolites, and bioactive natural products and serve as the active chromophore in green fluorescent protein. Recently, imidazolones have received attention for their ability to act as a nonaromatic amide bond bioisotere which improves pharmacological properties. Herein, we present a tandem amidine installation and cyclization with an adjacent ester to yield (4H)-imidazolone products. Using amino acid building blocks, we can access the first examples of α-chiral imidazolones that have been previously inaccessible. Additionally, our method is amenable to on-resin installation which can be seamlessly integrated into existing solid-phase peptide synthesis protocols. Finally, we show that peptide imidazolones are potent cis-amide bond surrogates that preorganize linear peptides for head-to-tail macrocyclization. This work represents the first general approach to the backbone and side-chain insertion of imidazolone bioisosteres at various positions in linear and cyclic peptides.

Growth Process of Fe–O Nanoclusters with Different Sizes Biosynthesized by Protein Nanocages
Wenming Wang - ,
Hongfang Xi - ,
Dan Fu - ,
Danyang Ma - ,
Wenjun Gong - ,
Yaqin Zhao - ,
Xiaomei Li - ,
Lijie Wu *- ,
Yu Guo *- ,
Guanghua Zhao *- , and
Hongfei Wang *
All protein-directed syntheses of metal nanoclusters (NCs) and nanoparticles (NPs) have attracted considerable attention because protein scaffolds provide a unique metal coordination environment and can adjust the shape and morphology of NCs and NPs. However, the detailed formation mechanisms of NCs or NPs directed by protein templates remain unclear. In this study, by taking advantage of the ferritin nanocage as a biotemplate to monitor the growth of Fe–O NCs as a function of time, we synthesized a series of iron NCs with different sizes and shapes and subsequently solved their corresponding three-dimensional atomic-scale structures by X-ray protein crystallography and cryo-electron microscopy. The time-dependent structure analyses revealed the growth process of these Fe–O NCs with the 4-fold channel of ferritin as nucleation sites. To our knowledge, the newly biosynthesized Fe35O23Glu12 represents the largest Fe–O NCs with a definite atomic structure. This study contributes to our understanding of the formation mechanism of iron NCs and provides an effective method for metal NC synthesis.

Rational Design of NIR-II G-Quadruplex Fluorescent Probes for Accurate In Vivo Tumor Metastasis Imaging
Ren-Xuan Wang - ,
Yifeng Ou - ,
Yushi Chen - ,
Tian-Bing Ren - ,
Lin Yuan - , and
Xiao-Bing Zhang
Accurate in vivo imaging of G-quadruplexes (G4) is critical for understanding the emergence and progression of G4-associated diseases like cancer. However, existing in vivo G4 fluorescent probes primarily operate within the near-infrared region (NIR-I), which limits their application accuracy due to the short emission wavelength. The transition to second near-infrared (NIR-II) fluorescent imaging has been of significant interest, as it offers reduced autofluorescence and deeper tissue penetration, thereby facilitating more accurate in vivo imaging. Nonetheless, the advancement of NIR-II G4 probes has been impeded by the absence of effective probe design strategies. Herein, through a “step-by-step” rational design approach, we have successfully developed NIRG-2, the first small-molecule fluorescent probe with NIR-II emission tailored for in vivo G4 detection. Molecular docking calculations reveal that NIRG-2 forms stable hydrogen bonds and strong π–π interactions with G4 structures, which effectively inhibit twisted intramolecular charge transfer (TICT) and, thereby, selectively illuminate G4 structures. Due to its NIR-II emission (940 nm), large Stokes shift (90 nm), and high selectivity, NIRG-2 offers up to 47-fold fluorescence enhancement and a tissue imaging depth of 5 mm for in vivo G4 detection, significantly outperforming existing G4 probes. Utilizing NIRG-2, we have, for the first time, achieved high-contrast visualization of tumor metastasis through lymph nodes and precise tumor resection. Furthermore, NIRG-2 proves to be highly effective and reliable in evaluating surgical and drug treatment efficacy in cancer lymphatic metastasis models. We are optimistic that this study not only provides a crucial molecular tool for an in-depth understanding of G4-related diseases in vivo but also marks a promising strategy for the development of clinical NIR-II G4-activated probes.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines
Kai Yang - ,
Bing Bai - ,
Jiaqi Lei - ,
Xinyang Yu - ,
Shaolong Qi - ,
Yangfan Wang - ,
Feihe Huang - ,
Zaizai Tong - , and
Guocan Yu *
Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Mechanochemical Synthesis of Perovskite Oxyhydrides: Insights from Shear Modulus
Yuki Sasahara - ,
Rina Terada - ,
Hiroki Ubukata - ,
Miho Asahi - ,
Daichi Kato - ,
Tatsuya Tsumori - ,
Morito Namba - ,
Zefeng Wei - ,
Cédric Tassel - , and
Hiroshi Kageyama *
Perovskite oxyhydrides have attracted recent attention due to their intriguing properties such as ionic conductivity and catalysis, but their repertoire is still restricted compared to perovskite oxynitrides and oxyfluorides. Historically, perovskite oxyhydrides have been prepared mostly by topochemical reactions and high-pressure (HP) reactions, while in this study, we employed a mechanochemical (MC) approach, which enables the synthesis of a series of ABO2H-type oxyhydrides, including those with the tolerance factor (t) much smaller than 1 (e.g., SrScO2H with t = 0.936) which cannot be obtained by HP synthesis. The octahedral tilting, often present in perovskite oxides, does not occur, suggesting that the lack of π-symmetry of the H 1s orbital and the large polarization destabilize tilted low-symmetry structures. Interestingly, SrCrO2H (t = 0.997), previously reported with the HP method, was not achieved with the MC method. A comparative analysis revealed a correlation between the feasibility of MC reactions and the (calculated) shear modulus of the starting reagents (binary oxides and hydrides). Notably, this indicator is not exclusive to oxyhydride perovskites but extends to oxide perovskites (SrMO3). This study demonstrates that MC synthesis offers unique opportunities not only to expand the compositional space in oxyhydrides in various structural types but also to provide a guide for the choice of starting materials for the synthesis of other compounds.

Formation of Chromophores from cis-Pinonaldehyde Aged in Highly Acidic Conditions
Cynthia Wong - ,
Jessica E. Pazienza - ,
Scott D. Rychnovsky - , and
Sergey A. Nizkorodov *
This publication is Open Access under the license indicated. Learn More
Sulfuric acid in the atmosphere can participate in acid-catalyzed and acid-driven reactions, including those within secondary organic aerosols (SOA). Previous studies have observed enhanced absorption at visible wavelengths and significant changes in the chemical composition when SOA was exposed to sulfuric acid. However, the specific chromophores responsible for these changes could not be identified. The goals of this study are to identify the chromophores and determine the mechanism of browning in highly acidified α-pinene SOA by following the behavior of specific common α-pinene oxidation products, namely, cis-pinonic acid and cis-pinonaldehyde, when they are exposed to highly acidic conditions. The products of these reactions were analyzed with ultra-performance liquid chromatography coupled with photodiode array spectrophotometry and high-resolution mass spectrometry, UV–vis spectrophotometry, and nuclear magnetic resonance spectroscopy. cis-Pinonic acid (2) was found to form homoterpenyl methyl ketone (4), which does not absorb visible radiation, while cis-pinonaldehyde (3) formed weakly absorbing 1-(4-(propan-2-ylidene)cyclopent-1-en-1-yl)ethan-1-one (5) and 1-(4-isopropylcyclopenta-1,3-dien-1-yl)ethan-1-one (6) via an acid-catalyzed aldol condensation. This chemistry could be relevant for environments characterized by high sulfuric acid concentrations, for example, during the transport of organic compounds from the lower to the upper atmosphere by fast updrafts.

Evolution and Interplay of Lithium Metal Interphase Components Revealed by Experimental and Theoretical Studies
Sha Tan - ,
Dacheng Kuai - ,
Zhiao Yu - ,
Saul Perez-Beltran - ,
Muhammad Mominur Rahman - ,
Kangxuan Xia - ,
Nan Wang - ,
Yuelang Chen - ,
Xiao-Qing Yang - ,
Jie Xiao - ,
Jun Liu - ,
Yi Cui - ,
Zhenan Bao - ,
Perla B. Balbuena *- , and
Enyuan Hu *
Lithium metal batteries (LMB) have high energy densities and are crucial for clean energy solutions. The characterization of the lithium metal interphase is fundamentally and practically important but technically challenging. Taking advantage of synchrotron X-ray, which has the unique capability of analyzing crystalline/amorphous phases quantitatively with statistical significance, we study the composition and dynamics of the LMB interphase for a newly developed important LMB electrolyte that is based on fluorinated ether. Pair distribution function analysis revealed the sequential roles of the anion and solvent in interphase formation during cycling. The relative ratio between Li2O and LiF first increases and then decreases during cycling, suggesting suppressed Li2O formation in both initial and long extended cycles. Theoretical studies revealed that in initial cycles, this is due to the energy barriers in many-electron transfer. In long extended cycles, the anion decomposition product Li2O encourages solvent decomposition by facilitating solvent adsorption on Li2O which is followed by concurrent depletion of both. This work highlights the important role of Li2O in transitioning from an anion-derived interphase to a solvent-derived one.

Facet-Dependent Oxygen Evolution Reaction Activity of IrO2 from Quantum Mechanics and Experiments
Soonho Kwon - ,
Kelsey A. Stoerzinger - ,
Reshma Rao - ,
Liang Qiao - ,
William A. Goddard III*- , and
Yang Shao-Horn *
The diversity of chemical environments present on unique crystallographic facets can drive dramatic differences in catalytic activity and the reaction mechanism. By coupling experimental investigations of five different IrO2 facets and theory, we characterize the detailed elemental steps of the surface redox processes and the rate-limiting processes for the oxygen evolution reaction (OER). The predicted complex evolution of surface adsorbates and the associated charge transfer as a function of applied potential matches well with the distinct redox features observed experimentally for the five facets. Our microkinetic model from grand canonical quantum mechanics (GC-QM) calculations demonstrates mechanistic differences between nucleophilic attack and O–O coupling across facets, providing the rates as a function of applied potential. These GC-QM calculations explain the higher OER activity observed on the (100), (001), and (110) facets and the lower activity observed for the (101) and (111) facets. This combined study with theory and experiment brings new insights into the structural features that either promote or hinder the OER activity of IrO2, which are expected to provide parallels in structural effects on other oxide surfaces.

An Active Site Tyr Residue Guides the Regioselectivity of Lysine Hydroxylation by Nonheme Iron Lysine-4-hydroxylase Enzymes through Proton-Coupled Electron Transfer
Yuanxin Cao - ,
Sam Hay - , and
Sam P. de Visser *
This publication is Open Access under the license indicated. Learn More
Lysine dioxygenase (KDO) is an important enzyme in human physiology involved in bioprocesses that trigger collagen cross-linking and blood pressure control. There are several KDOs in nature; however, little is known about the factors that govern the regio- and stereoselectivity of these enzymes. To understand how KDOs can selectively hydroxylate their substrate, we did a comprehensive computational study into the mechanisms and features of 4-lysine dioxygenase. In particular, we selected a snapshot from the MD simulation on KDO5 and created large QM cluster models (A, B, and C) containing 297, 312, and 407 atoms, respectively. The largest model predicts regioselectivity that matches experimental observation with rate-determining hydrogen atom abstraction from the C4–H position, followed by fast OH rebound to form 4-hydroxylysine products. The calculations show that in model C, the dipole moment is positioned along the C4–H bond of the substrate and, therefore, the electrostatic and electric field perturbations of the protein assist the enzyme in creating C4–H hydroxylation selectivity. Furthermore, an active site Tyr233 residue is identified that reacts through proton-coupled electron transfer akin to the axial Trp residue in cytochrome c peroxidase. Thus, upon formation of the iron(IV)-oxo species in the catalytic cycle, the Tyr233 phenol loses a proton to the nearby Asp179 residue, while at the same time, an electron is transferred to the iron to create an iron(III)-oxo active species. This charged tyrosyl residue directs the dipole moment along the C4–H bond of the substrate and guides the selectivity to the C4-hydroxylation of the substrate.

Development of the Squaramide Scaffold for High Potential and Multielectron Catholytes for Use in Redox Flow Batteries
Jacob S. Tracy - ,
Conor H. Broderick - , and
F. Dean Toste *
This publication is Open Access under the license indicated. Learn More
Nonaqueous organic redox flow batteries (N-ORFBs) are a promising technology for grid-scale storage of energy generated from intermittent renewable sources. Their primary benefit over traditional aqueous RFBs is the wide electrochemical stability window of organic solvents, but the design of catholyte materials, which can exploit the upper range of this window, has proven challenging. We report herein a new class of N-ORFB catholytes in the form of squaric acid quinoxaline (SQX) and squaric acid amide (SQA) materials. Mechanistic investigation of decomposition in battery-relevant conditions via NMR, HRMS, and electrochemical methods enabled a rational design approach to optimizing these scaffolds. Three lead compounds were developed: a highly stable one-electron SQX material with an oxidation potential of 0.51 V vs Fc/Fc+ that maintained 99% of peak capacity after 102 cycles (51 h) when incorporated into a 1.58 V flow battery; a high-potential one-electron SQA material with an oxidation potential of 0.81 V vs Fc/Fc+ that demonstrated negligible loss of redox active material as measured by pre- and postcycling CV peak currents when incorporated in a 1.63 V flow battery for 110 cycles over 29 h; and a proof-of-concept two-electron SQA catholyte material with oxidation potentials of 0.48 and 0.85 V vs Fc/Fc+ that demonstrated a capacity fade of just 0.56% per hour during static H-cell cycling. These findings expand the previously reported space of high-potential catholyte materials and showcase the power of mechanistically informed synthetic design for N-ORFB materials development.

Variable-Angle Surface Spectroscopy Reveals the Water Structure in the Stern Layer at Charged Aqueous Interfaces
Md. Mosfeq Uddin - ,
Md. Shafiul Azam - , and
Dennis K. Hore *
At charged aqueous interfaces, the second-order nonlinear optical response originates from water molecules within the diffuse part of the electrical double layer, which are ordered by the surface field and from water that additionally experiences chemical and physical interactions with the surface in the Stern layer. These two environments can either reinforce or diminish the overall signal and can be disentangled by varying the coherence length of their interaction with external laser fields. Here, we demonstrate a method in which the angle of incidence is varied to afford a significant change in the coherence length. When this technique was applied to the silica–water interface, it was observed that water molecules in the Stern and diffuse layers direct their hydrogen atoms toward the mineral surface at a low ionic strength and neutral pH. A decrease in the signal with increasing ionic strength is attributed to hydrated cation adsorption that competes with free water for deprotonated silanol sites.

Molecular-Scale Visualization of Steric Effects of Ligand Binding to Reconstructed Au(111) Surfaces
Liya Bi - ,
Sasawat Jamnuch - ,
Amanda Chen - ,
Alexandria Do - ,
Krista P. Balto - ,
Zhe Wang - ,
Qingyi Zhu - ,
Yufei Wang - ,
Yanning Zhang - ,
Andrea R. Tao *- ,
Tod A. Pascal *- ,
Joshua S. Figueroa *- , and
Shaowei Li *
This publication is Open Access under the license indicated. Learn More
Direct imaging of single molecules at nanostructured interfaces is a grand challenge with potential to enable new, precise material architectures and technologies. Of particular interest are the structural morphology and spectroscopic signatures of the adsorbed molecule, where modern probes are only now being developed with the necessary spatial and energetic resolution to provide detailed information at the molecule–surface interface. Here, we directly characterize the adsorption of individual m-terphenyl isocyanide ligands on a reconstructed Au(111) surface through scanning tunneling microscopy and inelastic electron tunneling spectroscopy. The site-dependent steric pressure of the various surface features alters the vibrational fingerprints of the m-terphenyl isocyanides, which are characterized with single-molecule precision through joint experimental and theoretical approaches. This study provides molecular-level insights into the steric-pressure-enabled surface binding selectivity as well as its effect on the chemical properties of individual surface-binding ligands.

Enzyme-Inspired Ligand Engineering of Gold Nanoclusters for Electrocatalytic Microenvironment Manipulation
Zhihe Liu - ,
Junmei Chen - ,
Bo Li - ,
De-en Jiang *- ,
Lei Wang *- ,
Qiaofeng Yao *- , and
Jianping Xie *
Natural enzymes intricately regulate substrate accessibility through specific amino acid sequences and folded structures at their active sites. Achieving such precise control over the microenvironment has proven to be challenging in nanocatalysis, especially in the realm of ligand-stabilized metal nanoparticles. Here, we use atomically precise metal nanoclusters (NCs) as model catalysts to demonstrate an effective ligand engineering strategy to control the local concentration of CO2 on the surface of gold (Au) NCs during electrocatalytic CO2 reduction reactions (CO2RR). The precise incorporation of two 2-thiouracil-5-carboxylic acid (TCA) ligands within the pocket-like cavity of [Au25(pMBA)18]− NCs (pMBA = para-mercaptobenzoic acid) leads to a substantial acceleration in the reaction kinetics of CO2RR. This enhancement is attributed to a more favorable microenvironment in proximity to the active site for CO2, facilitated by supramolecular interactions between the nucleophilic Nδ− of the pyrimidine ring of the TCA ligand and the electrophilic Cδ+ of CO2. A comprehensive investigation employing absorption spectroscopy, mass spectrometry, isotopic labeling measurements, electrochemical analyses, and quantum chemical computation highlights the pivotal role of local CO2 enrichment in enhancing the activity and selectivity of TCA-modified Au25 NCs for CO2RR. Notably, a high Faradaic efficiency of 98.6% toward CO has been achieved. The surface engineering approach and catalytic fundamentals elucidated in this study provide a systematic foundation for the molecular-level design of metal-based electrocatalysts.

Redox-Sensitive NiOx Stabilizing Perovskite Films for High-Performance Photovoltaics
Fang Cao - ,
Shaoqi Zhan - ,
Xinfeng Dai - ,
Fangwen Cheng - ,
Weixin Li - ,
Qifan Feng - ,
Xiaofeng Huang *- ,
Jun Yin *- ,
Jing Li - ,
Nanfeng Zheng - , and
Binghui Wu *
Metal halide perovskite materials inherently possess imperfections, particularly under nonequilibrium conditions, such as exposure to light or heat. To tackle this challenge, we introduced stearate ligand-capped nickel oxide (NiOx), a redox-sensitive metal oxide with variable valence, into perovskite intermediate films. The integration of NiOx improved the efficiency and stability of perovskite solar cells (PSCs) by offering multifunctional roles: (1) chemical passivation for ongoing defect repair, (2) energetic passivation to bolster defect tolerance, and (3) field-effect passivation to mitigate charge accumulation. Employing a synergistic approach that tailored these three passivation mechanisms led to a substantial increase in the devices’ efficiencies. The target cell (0.12 cm2) and module (18 cm2) exhibited efficiencies of 24.0 and 22.9%, respectively. Notably, the encapsulated modules maintained almost 100 and 87% of the initial efficiencies after operating for 1100 h at the maximum power point (60 °C, 50% RH) and 2000 h of damp-heat testing (85 °C, 85% RH), respectively. Outdoor real-time tests further validated the commercial viability of the NiOx-assisted PSMs. The proposed passivation strategy provides a practical and uncomplicated approach for fabricating high-efficiency and stable photovoltaics.

Reversible [4 + 1] Cycloaddition of Arenes by a “Naked” Acyclic Aluminyl Compound
Debotra Sarkar *- ,
Petra Vasko - ,
Aisling F. Roper - ,
Agamemnon E. Crumpton - ,
Matthew M. D. Roy - ,
Liam P. Griffin - ,
Charlotte Bogle - , and
Simon Aldridge *
This publication is Open Access under the license indicated. Learn More
The large steric profile of the N-heterocyclic boryloxy ligand, –OB(NDippCH)2, and its ability to stabilize the metal-centered HOMO, are exploited in the synthesis of the first example of a “naked” acyclic aluminyl complex, [K(2.2.2-crypt)][Al{OB(NDippCH)2}2]. This system, which is formed by substitution at AlI (rather than reduction of AlIII), represents the first O-ligated aluminyl compound and is shown to be capable of hitherto unprecedented reversible single-site [4 + 1] cycloaddition of benzene. This chemistry and the unusual regioselectivity of the related cycloaddition of anthracene are shown to be highly dependent on the availability (or otherwise) of the K+ countercation.

Cobalt-Catalyzed Acceptorless Dehydrogenation of Primary Amines to Nitriles
Haitao Tian - ,
Cai-Yun Ding - ,
Rong-Zhen Liao - ,
Man Li *- , and
Conghui Tang *
The direct double dehydrogenation from primary amines to nitriles without an oxidant or hydrogen acceptor is both intriguing and challenging. In this paper, we describe a non-noble metal catalyst capable of realizing such a transformation with high efficiency. A cobalt-centered N,N-bidentate complex was designed and employed as a metal–ligand cooperative dehydrogenation catalyst. Detailed kinetic studies, control experiments, and DFT calculations revealed the crucial hydride transfer, proton transfer, and hydrogen evolution processes. Finally, a tandem outer-sphere/inner-sphere mechanism was proposed for the dehydrogenation of amines to nitriles through an imine intermediate.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides
Han Ding - ,
Xiao-Lin Zhang - ,
Aoxin Guo - ,
Qian Ping Lee - ,
Chao Cai - ,
Ming Li - ,
Hongzhi Cao - , and
Xue-Wei Liu *
The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

Quantum Tunneling Instability in Pericyclic Reactions
Alexander Frenklach - ,
Hila Amlani - , and
Sebastian Kozuch *
Several cycloreversion reactions of the retro-Diels–Alder type were computationally assessed to understand their quantum tunneling (QT) reactivity. N2, CO, and other leaving groups were considered based on their strong exothermicity, as it reduces their thermodynamic and kinetic stabilities. Our results indicate that for many of these reactions, it is essential to take into account their QT decomposition rate, which can massively weaken their molecular stability and shorten their half-lives even at deep cryogenic temperatures. In practical terms, this indicates that many supposedly stable molecules will actually be unsynthesizable or unisolable, and therefore trying to prepare or detect them would be a futile attempt. In addition, we discuss the importance of tunneling to correctly understand the enthalpy of activation and the collective atomic effect on the tunneling kinetic isotope effects to test if third-row atoms can tunnel in a chemical reaction. This project raises the question of the importance of in silico chemistry to guide in vitro chemistry, especially in cases where the latter cannot solve its own uncertainties.

Direct Observation of Circularly Polarized Nonlinear Optical Activities in Chiral Hybrid Lead Halides
Sunhao Liu - ,
Xiaoming Wang - ,
Yixuan Dou - ,
Qian Wang - ,
Jiyoon Kim - ,
Carla Slebodnick - ,
Yanfa Yan - , and
Lina Quan *
This publication is Open Access under the license indicated. Learn More
Circularly polarized light emission is a crucial application in imaging, sensing, and photonics. However, utilizing low-energy photons to excite materials, as opposed to high-energy light excitation, can facilitate deep-tissue imaging and sensing applications. The challenge lies in finding materials capable of directly generating circularly polarized nonlinear optical effects. In this study, we introduce a chiral hybrid lead halide (CHLH) material system, R/S-DPEDPb3Br8·H2O (DPED = 1,2-diphenylethylenediammonium), which can directly produce circularly polarized second harmonic generation (CP-SHG) through linearly polarized infrared light excitation, exhibiting a polarization efficiency as high as 37% at room temperature. To understand the spin relaxation mechanisms behind the high polarization efficiency, we utilized two models, so-called D’yakonov–Perel’ (DP) and Bir–Aronov–Pikus (BAP) mechanisms. The unique zigzag inorganic frameworks within the hybrid structure are believed to reduce the dielectric confinement and exciton binding energy, thus enhancing spin polarization, especially in regions with a high excitation pump fluence based on the DP mechanism. In the case of low excitation pump fluence, the BAP mechanism dominates, as evidenced by the observed decrease in the polarization ratio from CP-SHG measurement. Using density functional theory analysis, we elucidate how the distinctive 8-coordination environment of lead bromide building blocks effectively suppresses spin–orbit coupling at the conduction band minimum. This suppression significantly diminishes spin-splitting, thereby slowing the spin relaxation rate.

Customizable Organic Charge-Transfer Cocrystals for the Dual-Mode Optoelectronics in the NIR (II) Window
Yue Yu - ,
Xing-Yu Xia - ,
Chao-Fei Xu - ,
Zhao-Ji Lv - ,
Xue-Dong Wang *- , and
Liang-Sheng Liao *
Organic molecules have been regarded as ideal candidates for near-infrared (NIR) optoelectronic active materials due to their customizability and ease of large-scale production. However, constrained by the intricate molecular design and severe energy gap law, the realization of optoelectronic devices in the second near-infrared (NIR (II)) region with required narrow band gaps presents more challenges. Herein, we have originally proposed a cocrystal strategy that utilizes intermolecular charge–transfer interaction to drive the redshift of absorption and emission spectra of a series BFXTQ (X = 0, 1, 2, 4) cocrystals, resulting in the spectra located at NIR (II) window and reducing the optical bandgap to ∼0.98 eV. Significantly, these BFXTQ-based optoelectronic devices can exhibit dual-mode optoelectronic characteristics. An investigation of a series of BFXTQ-based photodetectors exhibits detectivity (D*) surpassing 1013 Jones at 375 to 1064 nm with a maximum of 1.76 × 1014 Jones at 1064 nm. Moreover, the radiative transition of CT excitons within the cocrystals triggers NIR emission over 1000 nm with a photoluminescence quantum yield (PLQY) of ∼4.6% as well as optical waveguide behavior with a low optical-loss coefficient of 0.0097 dB/μm at 950 nm. These results promote the advancement of an emerging cocrystal approach in micro/nanoscale NIR multifunctional optoelectronics.

Phase Engineering of Zirconium MOFs Enables Efficient Osmotic Energy Conversion: Structural Evolution Unveiled by Direct Imaging
Cailing Chen - ,
Lingkun Meng - ,
Li Cao - ,
Daliang Zhang - ,
Shuhao An - ,
Lingmei Liu - ,
Jianjian Wang - ,
Guanxing Li - ,
Tingting Pan - ,
Jie Shen - ,
Zhijie Chen - ,
Zhan Shi - ,
Zhiping Lai *- , and
Yu Han *
Creating structural defects in a controlled manner within metal–organic frameworks (MOFs) poses a significant challenge for synthesis, and concurrently, identifying the types and distributions of these defects is also a formidable task for characterization. In this study, we demonstrate that by employing 2-sulfonylterephthalic acid as the ligand for synthesizing Zr (or Hf)-based MOFs, a crystal phase transformation from the common fcu topology to the rare jmt topology can be easily facilitated using a straightforward mixed-solvent strategy. The jmt phase, characterized by an extensively open framework, can be considered a derivative of the fcu phase, generated through the introduction of missing-cluster defects. We have explicitly identified both MOF phases, their intermediate states, and the novel core–shell structures they form using ultralow-dose high-resolution transmission electron microscopy. In addition to facilitating phase engineering, the incorporation of sulfonic groups in MOFs imparts ionic selectivity, making them applicable for osmotic energy harvesting through mixed matrix membrane fabrication. The membrane containing the jmt-phase MOF exhibits an exceptionally high peak power density of 10.08 W m–2 under a 50-fold salinity gradient (NaCl: 0.5 M|0.01 M), which surpasses the threshold of 5 W m–2 for commercial applications and can be attributed to the combination of large pore size, extensive porosity, and abundant sulfonic groups in this novel MOF material.

Late-Stage Saturation of Drug Molecules
De-Hai Liu - ,
Philipp M. Pflüger - ,
Andrew Outlaw - ,
Lukas Lückemeier - ,
Fuhao Zhang - ,
Clinton Regan - ,
Hamid Rashidi Nodeh - ,
Tim Cernak *- ,
Jiajia Ma *- , and
Frank Glorius *
This publication is Open Access under the license indicated. Learn More
The available methods of chemical synthesis have arguably contributed to the prevalence of aromatic rings, such as benzene, toluene, xylene, or pyridine, in modern pharmaceuticals. Many such sp2-carbon-rich fragments are now easy to synthesize using high-quality cross-coupling reactions that click together an ever-expanding menu of commercially available building blocks, but the products are flat and lipophilic, decreasing their odds of becoming marketed drugs. Converting flat aromatic molecules into saturated analogues with a higher fraction of sp3 carbons could improve their medicinal properties and facilitate the invention of safe, efficacious, metabolically stable, and soluble medicines. In this study, we show that aromatic and heteroaromatic drugs can be readily saturated under exceptionally mild rhodium-catalyzed hydrogenation, acid-mediated reduction, or photocatalyzed-hydrogenation conditions, converting sp2 carbon atoms into sp3 carbon atoms and leading to saturated molecules with improved medicinal properties. These methods are productive in diverse pockets of chemical space, producing complex saturated pharmaceuticals bearing a variety of functional groups and three-dimensional architectures. The rhodium-catalyzed method tolerates traces of dimethyl sulfoxide (DMSO) or water, meaning that pharmaceutical compound collections, which are typically stored in wet DMSO, can finally be reformatted for use as substrates for chemical synthesis. This latter application is demonstrated through the late-stage saturation (LSS) of 768 complex and densely functionalized small-molecule drugs.

Steering Selectivity in Electrocatalytic Furfural Reduction via Electrode–Electrolyte Interface Modification
Kaiyue Ji - ,
Yuanbo Liu - ,
Ye Wang - ,
Kejian Kong - ,
Jing Li - ,
Xiang Liu - , and
Haohong Duan *
Electrocatalytic reduction of biomass-derived furfural (FF) represents a sustainable route to produce furfuryl alcohol (FA) and 2-methylfuran (MF) as a value-added chemical and a biofuel, respectively. However, achieving high selectivity for MF as well as tuning the selectivity between FA and MF within one reaction system remain challenging. Herein, we have reported an electrode–electrolyte interface modification strategy, enabling FA and MF selectivity steering under the same reaction conditions. Specifically, by modifying copper (Cu) electrocatalysts with butyl trimethylammonium bromide (BTAB), we achieved a dramatic shift in selectivity from producing FA (selectivity: 83.8%; Faradaic efficiency, FE: 68.9%) to MF (selectivity: 80.1%; FE: 74.8%). We demonstrated that BTAB adsorption over Cu modulates the electrical double layer (EDL) structure, which repels interfacial water and weakens the hydrogen-bond (H-bond) network for proton transfer, thus impeding FF-to-FA conversion by suppression of the hydrogen atom transfer (HAT) process. On the contrary, FF-to-MF conversion was less affected. This work shows the potential of engineering of the electrode–electrolyte interface for selectivity control in electrocatalysis.

Probing Surface Transformations of Lanthanum Nickelate Electrocatalysts during Oxygen Evolution Reaction
Yi-Hsuan Wu - ,
Marcel Janák - ,
Paula M. Abdala - ,
Camelia Nicoleta Borca - ,
Anna Wach - ,
Agnieszka Kierzkowska - ,
Felix Donat - ,
Thomas Huthwelker - ,
Denis A. Kuznetsov *- , and
Christoph R. Müller *
Monitoring the spontaneous reconstruction of the surface of metal oxides under electrocatalytic reaction conditions is critical to identifying the active sites and establishing structure–activity relationships. Here, we report on a self-terminated surface reconstruction of Ruddlesden–Popper lanthanum nickel oxide (La2NiO4+δ) that occurs spontaneously during reaction with alkaline electrolyte species. Using a combination of high-resolution scanning transmission electron microscopy (HR-STEM), surface-sensitive X-ray photoelectron spectroscopy (XPS), and soft X-ray absorption spectroscopy (sXAS), as well as electrochemical techniques, we identify the structure of the reconstructed surface layer as an amorphous (oxy)hydroxide phase that features abundant under-coordinated nickel sites. No further amorphization of the crystalline oxide lattice (beyond the ∼2 nm thick layer formed) was observed during oxygen evolution reaction (OER) cycling experiments. Notably, the formation of the reconstructed surface layer increases the material’s oxygen evolution reaction (OER) activity by a factor of 45 when compared to that of the pristine crystalline surface. In contrast, a related perovskite phase, i.e., LaNiO3, did not show noticeable surface reconstruction, and also no increase in its OER activity was observed. This work provides detailed insight into a surface reconstruction behavior dictated by the crystal structure of the parent oxide and highlights the importance of surface dynamics under reaction conditions.

Lithium Superionic Conductive Nanofiber-Reinforcing High-Performance Polymer Electrolytes for Solid-State Batteries
Jiaying Peng - ,
Dawei Lu - ,
Shiqi Wu - ,
Na Yang - ,
Yujie Cui - ,
Zhaokun Ma - ,
Mengyue Liu - ,
Yongzheng Shi - ,
Yilin Sun *- ,
Jin Niu *- , and
Feng Wang *
Although composite solid-state electrolytes (CSEs) are considered promising ionic conductors for high-energy lithium metal batteries, their unsatisfactory ionic conductivity, low mechanical strength, poor thermal stability, and narrow voltage window limit their practical applications. We have prepared a new lithium superionic conductor (Li-HA-F) with an ultralong nanofiber structure and ultrahigh room-temperature ionic conductivity (12.6 mS cm–1). When it is directly coupled with a typical poly(ethylene oxide)-based solid electrolyte, the Li-HA-F nanofibers endow the resulting CSE with high ionic conductivity (4.0 × 10–4 S cm–1 at 30 °C), large Li+ transference number (0.66), and wide voltage window (5.2 V). Detailed experiments and theoretical calculations reveal that Li-HA-F supplies continuous dual-conductive pathways and results in stable LiF-rich interfaces, leading to its excellent performance. Moreover, the Li-HA-F nanofiber-reinforced CSE exhibits good heat/flame resistance and flexibility, with a high breaking strength (9.66 MPa). As a result, the Li/Li half cells fabricated with the Li-HA-F CSE exhibit good stability over 2000 h with a high critical current density of 1.4 mA cm–2. Furthermore, the LiFePO4/Li-HA-F CSE/Li and LiNi0.8Co0.1Mn0.1O2/Li-HA-F CSE/Li solid-state batteries deliver high reversible capacities over a wide temperature range with a good cycling performance.

Uncovering the Molecular Composition and Architecture of the Bacillus subtilis Biofilm via Solid-State NMR Spectroscopy
Yi Xue - ,
Chenjie Yu - ,
Han Ouyang - ,
Jiaofang Huang *- , and
Xue Kang *
ACS Editors' Choice® is a collection designed to feature scientific articles of broad public interest. Read the latest articles
The complex and dynamic compositions of biofilms, along with their sophisticated structural assembly mechanisms, endow them with exceptional capabilities to thrive in diverse conditions that are typically unfavorable for individual cells. Characterizing biofilms in their native state is significantly challenging due to their intrinsic complexities and the limited availability of noninvasive techniques. Here, we utilized solid-state nuclear magnetic resonance (NMR) spectroscopy to analyze Bacillus subtilis biofilms in-depth. Our data uncover a dynamically distinct organization within the biofilm: a dominant, hydrophilic, and mobile framework interspersed with minor, rigid cores of limited water accessibility. In these heterogeneous rigid cores, the major components are largely self-assembled. TasA fibers, the most robust elements, further provide a degree of mechanical support for the cell aggregates and some lipid vesicles. Notably, rigid cell aggregates can persist even without the major extracellular polymeric substance (EPS) polymers, although this leads to slight variations in their rigidity and water accessibility. Exopolysaccharides are exclusively present in the mobile domain, playing a pivotal role in its water retention property. Specifically, all water molecules are tightly bound within the biofilm matrix. These findings reveal a dual-layered defensive strategy within the biofilm: a diffusion barrier through limited water mobility in the mobile phase and a physical barrier posed by limited water accessibility in the rigid phase. Complementing these discoveries, our comprehensive, in situ compositional analysis is not only essential for delineating the sophisticated biofilm architecture but also reveals the presence of alternative genetic mechanisms for synthesizing exopolysaccharides beyond the known pathway.

Manipulation of Luminescence via Surface Site Occupation in Ln3+-Doped Nanocrystals
Rui Shi - ,
Litian Lin - ,
Zijun Wang - ,
Qilin Zou - , and
Anja-Verena Mudring *
This publication is Open Access under the license indicated. Learn More
Ln3+-doped (Ln = lanthanide) nanocrystals are garnering strong interest for their potential as optical materials in various applications. For that reason, a thorough understanding of photophysical processes and ways to tune them in these materials is of great importance. This study, using Eu3+-doped Sr2YF7 as a well-suited model system, underscores the (not unexpected) significance of surface site occupation of Ln3+ and also challenges the prevailing views about their contribution to the luminescence of the system. High-temperature cation exchange and epitaxial shell growth allow nanocrystals to exclusively feature Eu3+ residing at the surface or in the interior, thereby separating their spectral responses. Meticulous experiments reveal that nanocrystals with high doping concentrations exhibit luminescence primarily from surface Eu3+, in contrast to the popular belief that luminescence from surface Ln3+ is largely negligible. The present study shows, on the one hand, the necessity to revise common ideas and also reveals the potential for manipulating the luminescence of such materials through an, until now, unperceived way of surface engineering.

Dicyanorhodanine-Pyrrole Conjugates for Visible Light-Driven Quantitative Photoswitching in Solution and the Solid State
Parag Das - ,
Nathan J. Grinalds - ,
Ion Ghiviriga - ,
Khalil A. Abboud - ,
Łukasz Dobrzycki - ,
Jiangeng Xue *- , and
Ronald K. Castellano *
Small molecule photoswitches capable of toggling between two distinct molecular states in response to light are versatile tools to monitor biological processes, control photochemistry, and design smart materials. In this work, six novel dicyanorhodanine-based pyrrole-containing photoswitches are reported. The molecular design avails both the Z and E isomers from synthesis, where each can be isolated using chromatographic techniques. Inter- and intramolecular hydrogen bonding (H-bonding) interactions available to the E and Z isomers, respectively, uniquely impart thermal stability to each isomer over long time periods. Photoisomerization could be assessed by solution NMR and UV–vis spectroscopic techniques along with complementary ground- and excited-state computational studies, which show good agreement. Quantitative E → Z isomerization occurs upon 523 nm irradiation of the parent compound (where R = H) in solution, whereas Z → E isomerization using 404 nm irradiation offers a photostationary state (PSS) ratio of 84/16 (E/Z). Extending the π-conjugation of the pyrrole unit (where R = p-C6H4–OMe) pushes the maximum absorption to the yellow-orange region of the visible spectrum and allows bidirectional quantitative isomerization with 404 and 595 nm excitation. Comparator molecules have been prepared to report how the presence or absence of H-bonding affects the photoswitching behavior. Finally, studies of the photoswitches in neat films and photoinactive polymer matrices reveal distinctive structural and optical properties of the Z and E isomers and ultimately afford reversible photoswitching to spectrally unique PSSs using visible light sources including the Sun.

Protein Tyrosine Amination: Detection, Imaging, and Chemoproteomic Profiling with Synthetic Probes
Lei Chen - ,
Tonghua Yang - ,
Xue Sun - ,
Catherine C.L. Wong *- , and
Dan Yang *
This publication is Open Access under the license indicated. Learn More
Protein tyrosine nitration (PTN) by oxidative and nitrative stress is a well-known post-translational modification that plays a role in the initiation and progression of various diseases. Despite being recognized as a stable modification for decades, recent studies have suggested the existence of a reduction in PTN, leading to the formation of 3-aminotyrosine (3AT) and potential denitration processes. However, the vital functions of 3AT-containing proteins are still unclear due to the lack of selective probes that directly target the protein tyrosine amination. Here, we report a novel approach to label and enrich 3AT-containing proteins with synthetic salicylaldehyde (SAL)-based probes: SALc-FL with a fluorophore and SALc-Yn with an alkyne tag. These probes exhibit high selectivity and efficiency in labeling and can be used in cell lysates and live cells. More importantly, SALc-Yn offers versatility when integrated into multiple platforms by enabling proteome-wide quantitative profiling of cell nitration dynamics. Using SALc-Yn, 355 proteins were labeled, enriched, and identified to carry the 3AT modification in oxidatively stressed RAW264.7 cells. These findings provide compelling evidence supporting the involvement of 3AT as a critical intermediate in nitrated protein turnover. Moreover, our probes serve as powerful tools to investigate protein nitration and denitration processes, and the identification of 3AT-containing proteins contributes to our understanding of PTN dynamics and its implications in cellular redox biology.

Suppressing Metal Leaching and Sintering in Hydroformylation Reaction by Modulating the Coordination of Rh Single Atoms with Reactants
Zhounan Yu - ,
Shengxin Zhang - ,
Leilei Zhang *- ,
Xiaoyan Liu - ,
Zhenghao Jia - ,
Lin Li - ,
Na Ta - ,
An Wang - ,
Wei Liu *- ,
Aiqin Wang *- , and
Tao Zhang
Hydroformylation reaction is one of the largest homogeneously catalyzed industrial processes yet suffers from difficulty and high cost in catalyst separation and recovery. Heterogeneous single-atom catalysts (SACs), on the other hand, have emerged as a promising alternative due to their high initial activity and reasonable regioselectivity. Nevertheless, the stability of SACs against metal aggregation and leaching during the reaction has rarely been addressed. Herein, we elucidate the mechanism of Rh aggregation and leaching by investigating the structural evolution of Rh1@silicalite-1 SAC in response to different adsorbates (CO, H2, alkene, and aldehydes) by using diffuse reflectance infrared Fourier transform spectroscopy, X-ray adsorption fine structure, and scanning transmission electron microscopy techniques and kinetic studies. It is discovered that the aggregation and leaching of Rh are induced by the strong adsorption of CO and aldehydes on Rh, as well as the reduction of Rh3+ by CO/H2 which weakens the binding of Rh with support. In contrast, alkene effectively counteracts this effect by the competitive adsorption on Rh atoms with CO/aldehyde, and the disintegration of Rh clusters. Based on these results, we propose a strategy to conduct the reaction under conditions of high alkene concentration, which proves to be able to stabilize Rh single atom against aggregation and/or leaching for more than 100 h time-on-stream.

Photocatalytic Conversion of Methane to Ethanol at a Three-Phase Interface with Concentration-Matched Hydroxyl and Methyl Radicals
Chun He - ,
Lan Shang - ,
Hongfu Zhu - ,
Lianchao Yu - ,
Lingzhi Wang *- , and
Jinlong Zhang *
The direct oxidation of CH4 to C2H5OH is attractive but challenging owing to the intricate processes involving carbon-chain growth and hydroxylation simultaneously. The inherent difficulty arises from the strong tendency of CH4 to overoxidize in the commonly used pressurized powder suspension systems rich in reactive oxygen radicals (ROR), which are specifically designed for CH4 concentration and activation. Meanwhile, the strong tendency of nucleophilic attack of potent ROR on the C–C bond of the resulting product C2H5OH ultimately leads to a higher selectivity for C1 oxygenates. This study addresses this multifaceted issue by designing a three-phase interface based on a hydrophilic floating Fe(III)-cross-linked macroporous alginate hydrogel film encapsulated with C3N4 [Fe(III)@ACN] to simultaneously enhance the accessibility of H2O and CH4 molecules to the active sites and species within the macroporous channel. The hydrophilic properties of Fe(III)@ACN allow the in situ production of H2O2 from C3N4 through the water oxidation reaction under irradiation. The concurrent photoinduced Fe(II) triggers Fenton reaction with H2O2 to produce •OH. The enhanced mass transfer of CH4 at the three-phase interface ensures the efficient formation of •CH3 by reacting with •OH, ultimately facilitating carbon-chain growth in the conversion pathway from CH4 to CH3OH and finally to C2H5OH with •CH3 and •OH present in comparable concentrations. Thus, the Fe(III)@ACN catalyst exhibits a remarkable 96% selectivity for alcohol, achieving a 90% selectivity for C2H5OH in the alcohol products. The C2H5OH production rate reaches 171.7 μmol g–1 h–1 without the need for precious-metal additive.

Tethered Helical Ladder-Type Aromatic Lactams
Huidong Xie - ,
Zuo Xiao *- ,
Yixiao Song - ,
Ke Jin - ,
Hongxing Liu - ,
Erjun Zhou - ,
Jing Cao - ,
Jiangzhao Chen - ,
Junqiao Ding - ,
Chenyi Yi - ,
Xingxing Shen *- ,
Chuantian Zuo *- , and
Liming Ding *
Tethered nonplanar aromatics (TNAs) make up an important class of nonplanar aromatic compounds showing unique features. However, the knowledge on the synthesis, structures, and properties of TNAs remains insufficient. In this work, a new type of TNAs, the tethered aromatic lactams, is synthesized via Pd-catalyzed consecutive intramolecular direct arylations. These molecules possess a helical ladder-type conjugated system of up to 13 fused rings. The overall yields ranged from 3.4 to 4.3%. The largest of the tethered aromatic lactams, 6L-Bu-C14, demonstrates a guest-adaptive hosting capability of TNAs for the first time. When binding fullerene guests, the cavity of 6L-Bu-C14 became more circular to better accommodate spherical fullerene molecules. The host–guest interaction is thoroughly studied by X-ray crystallography, theoretical calculations, fluorescence titration, and nuclear magnetic resonance (NMR) titration experiments. 6L-Bu-C14 shows stronger binding with C70 than with C60 due to the better convex–concave π–π interaction. P and M enantiomers of all tethered aromatic lactams show distinct and persistent chiroptical properties and demonstrate the potential of chiral TNAs as circularly polarized luminescence (CPL) emitters.

Supramolecular Assembly in Live Cells Mapped by Real-Time Phasor-Fluorescence Lifetime Imaging
Yong Ren - ,
Zhixuan Zhou - ,
Konrad Maxeiner - ,
Anke Kaltbeitzel - ,
Iain Harley - ,
Jiaqi Xing - ,
Yingke Wu - ,
Manfred Wagner - ,
Katharina Landfester - ,
Ingo Lieberwirth - ,
Tanja Weil *- , and
David Y. W. Ng *
This publication is Open Access under the license indicated. Learn More
The complex dynamics and transience of assembly pathways in living systems complicate the understanding of these molecular to nanoscale processes. Current technologies are unable to track the molecular events leading to the onset of assembly, where real-time information is imperative to correlate their rich biology. Using a chemically designed pro-assembling molecule, we map its transformation into nanofibers and their fusion with endosomes to form hollow fiber clusters. Tracked by phasor-fluorescence lifetime imaging (phasor-FLIM) in epithelial cells (L929, A549, MDA-MB 231) and correlative light-electron microscopy and tomography (CLEM), spatiotemporal splicing of the assembly events shows time-correlated metabolic dysfunction. The biological impact begins with assembly-induced endosomal disruption that reduces glucose transport into the cells, which, in turn, stymies mitochondrial respiration.

Diffusional Electron Transport Coupled to Thermodynamically Driven Electron Transfers in Redox-Conductive Multivariate Metal–Organic Frameworks
Jingguo Li - ,
Amol Kumar - , and
Sascha Ott *
This publication is Open Access under the license indicated. Learn More
The development of redox-conductive metal–organic frameworks (MOFs) and the fundamental understanding of charge propagation through these materials are central to their applications in energy storage, electronics, and catalysis. To answer some unresolved questions about diffusional electron hopping transport and redox conductivity, mixed-linker MOFs were constructed from two statistically distributed redox-active linkers, pyromellitic diimide bis-pyrazolate (PMDI) and naphthalene diimide bis-pyrazolate (NDI), and grown as crystalline thin films on conductive fluorine-doped tin oxide (FTO). Owing to the distinct redox properties of the linkers, four well-separated and reversible redox events are resolved by cyclic voltammetry, and the mixed-linker MOFs can exist in five discrete redox states. Each state is characterized by a unique spectroscopic signature, and the interconversions between the states can be followed spectroscopically under operando conditions. With the help of pulsed step-potential spectrochronoamperometry, two modes of electron propagation through the mixed-linker MOF are identified: diffusional electron hopping transport between linkers of the same type and a second channel that arises from thermodynamically driven electron transfers between linkers of different types. Corresponding to the four redox events of the mixed-linker MOFs, four distinct bell-shaped redox conductivity profiles are observed at a steady state. The magnitude of the maximum redox conductivity is evidenced to be dependent on the distance between redox hopping sites, analogous to the situation for apparent electron diffusion coefficients, Deapp, that are obtained in transient experiments. The design of mixed-linker redox-conductive MOFs and detailed studies of their charge transport properties present new opportunities for future applications of MOFs, in particular, within electrocatalysis.

π-Extended Nonfullerene Acceptor for Compressed Molecular Packing in Organic Solar Cells To Achieve over 20% Efficiency
Yuandong Sun - ,
Liang Wang - ,
Chuanhang Guo - ,
Jinyi Xiao - ,
Chenhao Liu - ,
Chen Chen - ,
Weiyi Xia - ,
Zirui Gan - ,
Jingchao Cheng - ,
Jinpeng Zhou - ,
Zhenghong Chen - ,
Jing Zhou - ,
Dan Liu - ,
Tao Wang - , and
Wei Li *
Organic photovoltaics (OPVs) suffer from a trade-off between efficient charge transport and suppressed nonradiative recombination due to the aggregation-induced luminance quenching of organic semiconductors. To resolve this grand challenge, a π-extended nonfullerene acceptor (NFA) B6Cl with large voids among the honeycomb network is designed and introduced into photovoltaic systems. We find that the presence of a small amount of (i.e., 0.5 or 1 wt %) B6Cl can compress the molecular packing of the host acceptor L8-BO, leading to shortened π–π stacking distance from 3.59 to 3.50 Å (that will improve charge transport) together with ordered alkyl chain packing (that will inhibit nonradiative energy loss due to the suppressed C–C and C–H bonds vibrations), as validated by high-energy X-ray scattering measurements. This morphology transformation ultimately results in simultaneously improved JSC, FF, and VOC of OPVs. As a result, the maximum PCEs of PM6:L8-BO and D18:L8-BO are increased from 19.1 and 19.3% to 19.8 and 20.2%, respectively, which are among the highest values for single-junction OPVs. The university of B6Cl to increase the performance of OPVs is further evidenced in a range of polymer:NFA OPVs.

Reconstructable Carbon Monolayer-MoS2 Intercalated Heterostructure Enabled by Atomic Layers-Confined Topotactic Transformation for Ultrafast Lithium Storage
Kexuan Liao - ,
Lu Chen - ,
Ruijin Meng - ,
Yutong Feng - ,
Shuo Meng - ,
Hang Lu - ,
Jie Ma - ,
Chengxin Peng - ,
Chi Zhang *- , and
Jinhu Yang *
The intercalation structure of two-dimensional materials with expanded interlayer distance can facilitate mass transport, which is promising in fast-charging lithium-ion batteries (LIBs). However, the designed intercalation structures will be pulverized and destroyed under tough working conditions, causing overall performance deterioration of the batteries. Here, we present that an intercalated heterostructure made of the typical layered material of MoS2 intercalated by N-doped graphene-like carbon monolayer (MoS2/g-CM) through a polymer intercalation strategy exhibits a unique behavior of reversible reconstructability as an LIB anode during cycling. A mechanism of “carbon monolayers-confined topotactic transformation” is proposed, which is evidenced by substantial in/ex situ characterizations. The intercalated heterostructure of MoS2/g-CM featuring a reconstructable property and efficient interlayer electron/ion transport exhibits an unprecedented rate capability up to 50 A g–1 and outstanding long cyclability. Moreover, the proposed strategy based on g-CM intercalation has been extended to the MoSe2 system, also realizing reconstructability of the intercalated heterostructure and improved LIB performance, demonstrating its versatility and great potential in applications.

Overdestabilization vs Overstabilization in the Theoretical Analysis of f-Orbital Covalency
Kirill D. Shumilov - ,
Andrew J. Jenkins - ,
Henry S. La Pierre *- ,
Bess Vlaisavljevich *- , and
Xiaosong Li *
The complex nature of the f-orbital electronic structures and their interaction with the chemical environment pose significant computational challenges. Advanced computational techniques that variationally include scalar relativities and spin–orbit coupling directly at the molecular orbital level have been developed to address this complexity. Among these, variational relativistic multiconfigurational multireference methods stand out for their high accuracy and systematic improvement in studies of f-block complexes. Additionally, these advanced methods offer the potential for calibrating low-scaling electronic structure methods such as density functional theory. However, studies on the Cl K-edge X-ray absorption spectra of the [Ce(III)Cl6]3– and [Ce(IV)Cl6]2– complexes show that time-dependent density functional theory with approximate exchange–correlation kernels can lead to inaccuracies, resulting in an overstabilization of 4f orbitals and incorrect assessments of covalency. In contrast, approaches utilizing small active space wave function methods may understate the stability of these orbitals. The results herein demonstrate the need for large active space, multireference, and variational relativistic methods in studying f-block complexes.

Elucidating the Role of Reduction Kinetics in the Phase-Controlled Growth on Preformed Nanocrystal Seeds: A Case Study of Ru
Quynh N. Nguyen - ,
Eun Mi Kim - ,
Yong Ding - ,
Annemieke Janssen - ,
Chenxiao Wang - ,
Kei Kwan Li - ,
Junseok Kim - ,
Kristen A. Fichthorn *- , and
Younan Xia *
This publication is Open Access under the license indicated. Learn More
This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3–7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

Photoinduced Pd-Catalyzed Enantioselective Carboamination of Dienes via Aliphatic C–H Bond Elaboration
Xiao-Yun Ruan - ,
Dan-Xing Wu - ,
Wen-Ao Li - ,
Zihan Lin - ,
Mostafa Sayed - ,
Zhi-Yong Han *- , and
Liu-Zhu Gong *
Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C–H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)–H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)–H bearing partners.

Aliovalent Substitution Tunes Physical Properties in a Conductive Bis(dithiolene) Two-Dimensional Metal–Organic Framework
Lei Wang - ,
Andrea Daru - ,
Bhavnesh Jangid - ,
Jie-Hao Chen - ,
Ningxin Jiang - ,
Shrayesh N. Patel - ,
Laura Gagliardi - , and
John S. Anderson *
Two-dimensional conductive metal–organic frameworks have emerged as promising electronic materials for applications in (opto)electronic, thermoelectric, magnetic, electrocatalytic, and energy storage devices. Many bottom-up or postsynthetic protocols have been developed to isolate these materials or further modulate their electronic properties. However, some methodologies commonly used in classic semiconductors, notably, aliovalent substitution, are conspicuously absent. Here, we demonstrate how aliovalent Fe(III) to Ni(II) substitution enables the isolation of a Ni bis(dithiolene) material from a previously reported Fe analogue. Detailed characterization supports the idea that aliovalent substitution of Fe(III) to Ni(II) results in an in situ oxidation of the organic dithiolene linker. This substitution-induced redox tuning modulates the electronic properties in the system, leading to higher electrical conductivity and Hall mobility but slightly lower carrier densities and weaker antiferromagnetic interactions. Moreover, this aliovalent substitution improves the material’s electrochemical stability and thus enables pseudocapacitive behavior in the Ni material. These results demonstrate how classic aliovalent substitution strategies in semiconductors can also be leveraged in conductive MOFs and add further support to this class of compounds as emerging electronic materials.

Multiphosphorylation-Dependent Recognition of Anti-pS2 Antibodies against RNA Polymerase II C-Terminal Domain Revealed by Chemical Synthesis
Emanuele Piemontese - ,
Alina Herfort - ,
Yulia Perevedentseva - ,
Heiko M. Möller - , and
Oliver Seitz *
This publication is Open Access under the license indicated. Learn More
Phosphorylation is a major constituent of the CTD code, which describes the set of post-translational modifications on 52 repeats of a YSPTSPS consensus heptad that orchestrates the binding of regulatory proteins to the C-terminal domain (CTD) of RNA polymerase II. Phospho-specific antibodies are used to detect CTD phosphorylation patterns. However, their recognition repertoire is underexplored due to limitations in the synthesis of long multiphosphorylated peptides. Herein, we describe the development of a synthesis strategy that provides access to multiphosphorylated CTD peptides in high purity without HPLC purification for immobilization onto microtiter plates. Native chemical ligation was used to assemble 12 heptad repeats in various phosphoforms. The synthesis of >60 CTD peptides, 48–90 amino acids in length and containing up to 6 phosphosites, enabled a detailed and rapid analysis of the binding characteristics of different anti-pSer2 antibodies. The three antibodies tested showed positional selectivity with marked differences in the affinity of the antibodies for pSer2-containing peptides. Furthermore, the length of the phosphopeptides allowed a systematic analysis of the multivalent chelate-type interactions. The absence of multivalency-induced binding enhancements is probably due to the high flexibility of the CTD scaffold. The effect of clustered phosphorylation proved to be more complex. Recognition of pSer2 by anti-pSer2-antibodies can be prevented and, perhaps surprisingly, enhanced by the phosphorylation of “bystander” amino acids in the vicinity. The results have relevance for functional analysis of the CTD in cell biological experiments.

Free Radicals Generated in Perfluorocarbon–Water (Liquid–Liquid) Interfacial Contact Electrification and Their Application in Cancer Therapy
Haimei Li - ,
Zichen Wang - ,
Xu Chu - ,
Yi Zhao - ,
Guangqin He - ,
Yulin Hu - ,
Yi Liu *- ,
Zhong Lin Wang *- , and
Peng Jiang *
Electron transfer during solid–liquid contact electrification has been demonstrated to produce reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and superoxide anion radicals (•O2–). Here, we show that such a process also occurs in liquid–liquid contact electrification. By preparing perfluorocarbon nanoemulsions to construct a perfluorocarbon–water “liquid–liquid” interface, we confirmed that electrons were transferred from water to perfluorocarbon in ultrasonication-induced high-frequency liquid–liquid contact to produce •OH and •O2–. The produced ROS could be applied to ablate tumors by triggering large-scale immunogenic cell death in tumor cells, promoting dendritic cell maturation and macrophage polarization, ultimately activating T cell-mediated antitumor immune response. Importantly, the raw material for producing •OH is water, so the tumor therapy is not limited by the endogenous substances (O2, H2O2, etc.) in the tumor microenvironment. This work provides new perspectives for elucidating the mechanism of generation of free radicals in liquid–liquid contact and provides an excellent tumor therapeutic modality.

Tetramerization of BEB-Doped Phenalenyls to Obtain (BE)8-[16]Annulenes (E = N, O)
Alexander S. Scholz - ,
Michael Bolte - ,
Alexander Virovets - ,
Eugenia Peresypkina - ,
Hans-Wolfram Lerner - ,
Cate S. Anstöter *- , and
Matthias Wagner *
Two (BE)8-[16]annulenes were prepared and fully characterized by experimental and quantum-chemical means (1, E = N; 2, E = O). The 1,8-naphthalenediyl-bridged diborane(6) 3 served as their common starting material, which was treated with [Al(NH3)6]Cl3 to form 1 (91% yield) or with 1,8-naphthalenediboronic acid anhydride to form 2 (93% yield). As a result, the heteroannulenes 1 and 2 are supported by four aromatic “clamps” and may also be viewed as NH- or O-bridged cyclic tetramers of BNB- or BOB-doped phenalenyls. X-ray crystallography on mono-, di-, and tetraadducts 2·thf, 2·py2, and 2·py4 showed that 2 is an oligotopic Lewis acid (thf/py: tetrahydrofuran/pyridine donor). The applicability of 2 also as a Lewis basic ligand in coordination chemistry was demonstrated by the synthesis of the mononuclear Ag+ complex [Ag(py)2(2·py4)]+ and the dinuclear Pb2+ complex 6. During the assembly of 6, the rearrangement of 2 led to the formation of two (BO)9-macrocycles linked by two BOB-phenalenyls to form a nanometer-sized cage with four negatively charged, tetracoordinated B atoms. Both 1 and 2 show several redox waves in the cathodic regions of the cyclic voltammograms. An in-depth assessment of the consequences of electron injection on the aromaticity of 1 and 2 was achieved by electronic structure calculations. 1 and 2 are proposed to exhibit aromatic switching capabilities in the [16]annulene motif.

Can the Rate of a Catalytic Turnover Be Altered by Ligands in the Absence of Direct Binding Interactions?
Jacklyn N. Hall - ,
Stephen P. Vicchio - ,
A. Jeremy Kropf - ,
Massimiliano Delferro - , and
Praveen Bollini *
Second sphere coordination effects ubiquitous in enzymatic catalysis occur through direct interactions, either covalent or non-covalent, with reaction intermediates and transition states. We present herein evidence of indirect second sphere coordination effects in which ligation of water/alkanols far removed from the primary coordination sphere of the active site nevertheless alter energetic landscapes within catalytic redox cycles in the absence of direct physicochemical interactions with surface species mediating catalytic turnovers. Density functional theory, in situ X-ray absorption and infrared spectroscopy, and a wide array of steady-state and transient CO oxidation rate data suggest that the presence of peripheral water renders oxidation half-cycles within two-electron redox cycles over μ3-oxo-bridged trimers in MIL-100(M) more kinetically demanding. Communication between ligated water and the active site appears to occur through the Fe–O–Fe backbone, as inferred from spin density variations on the central μ3-oxygen ‘junction’. Evidence is provided for the generality of these second sphere effects in that they influence different types of redox half-cycles or metals, and can be amplified or attenuated through choice of coordinating ligand. Specifically in the case of MIL-100(M) materials, the Cr isostructure can be made to kinetically mimic the Fe variant by disproportionately hindering oxidation half-cycles relative to the reduction half-cycles. Kinetic and spectroscopic inferences presented here significantly expand both the conceptual definition of second sphere effects as well as the palette of synthetic levers available for tuning catalytic redox performance through chemical ligation.

Consequences of Vibrational Strong Coupling on Supramolecular Polymerization of Porphyrins
Kripa Joseph - ,
Bas de Waal - ,
Stef A. H. Jansen - ,
Joost J. B. van der Tol - ,
Ghislaine Vantomme - , and
E. W. Meijer *
This publication is Open Access under the license indicated. Learn More
Supramolecular polymers display interesting optoelectronic properties and, thus, deploy multiple applications based on their molecular arrangement. However, controlling supramolecular interactions to achieve a desirable molecular organization is not straightforward. Over the past decade, light–matter strong coupling has emerged as a new tool for modifying chemical and material properties. This novel approach has also been shown to alter the morphology of supramolecular organization by coupling the vibrational bands of solute and solvent to the optical modes of a Fabry–Perot cavity (vibrational strong coupling, VSC). Here, we study the effect of VSC on the supramolecular polymerization of chiral zinc-porphyrins (S-Zn) via a cooperative effect. Electronic circular dichroism (ECD) measurements indicate that the elongation temperature (Te) of the supramolecular polymerization is lowered by ∼10 °C under VSC. We have also generalized this effect by exploring other supramolecular systems under strong coupling conditions. The results indicate that the solute–solvent interactions are modified under VSC, which destabilizes the nuclei of the supramolecular polymer at higher temperatures. These findings demonstrate that the VSC can indeed be used as a tool to control the energy landscape of supramolecular polymerization. Furthermore, we use this unique approach to switch between the states formed under ON- and OFF-resonance conditions, achieved by simply tuning the optical cavity in and out of resonance.

Chemical Proteomics Strategies for Analyzing Protein Lipidation Reveal the Bacterial O-Mycoloylome
Nicholas Banahene - ,
Trenton M. Peters-Clarke - ,
Kyle J. Biegas - ,
Evgenia Shishkova - ,
Elizabeth M. Hart - ,
Amelia C. McKitterick - ,
Nikolas H. Kambitsis - ,
Ulysses G. Johnson - ,
Thomas G. Bernhardt - ,
Joshua J. Coon - , and
Benjamin M. Swarts *
This publication is Open Access under the license indicated. Learn More
Protein lipidation dynamically controls protein localization and function within cellular membranes. A unique form of protein O-fatty acylation in Corynebacterium, termed protein O-mycoloylation, involves the attachment of mycolic acids─unusually large and hydrophobic fatty acids─to serine residues of proteins in these organisms’ outer mycomembrane. However, as with other forms of protein lipidation, the scope and functional consequences of protein O-mycoloylation are challenging to investigate due to the inherent difficulties of enriching and analyzing lipidated peptides. To facilitate the analysis of protein lipidation and enable the comprehensive profiling and site mapping of protein O-mycoloylation, we developed a chemical proteomics strategy integrating metabolic labeling, click chemistry, cleavable linkers, and a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method employing LC separation and complementary fragmentation methods tailored to the analysis of lipophilic, MS-labile O-acylated peptides. Using these tools in the model organism Corynebacterium glutamicum, we identified approximately 30 candidate O-mycoloylated proteins, including porins, mycoloyltransferases, secreted hydrolases, and other proteins with cell envelope-related functions─consistent with a role for O-mycoloylation in targeting proteins to the mycomembrane. Site mapping revealed that many of the proteins contained multiple spatially proximal modification sites, which occurred predominantly at serine residues surrounded by conformationally flexible peptide motifs. Overall, this study (i) discloses the putative protein O-mycoloylome for the first time, (ii) yields new insights into the undercharacterized proteome of the mycomembrane, which is a hallmark of important pathogens (e.g., Corynebacterium diphtheriae, Mycobacterium tuberculosis), and (iii) provides generally applicable chemical strategies for the proteomic analysis of protein lipidation.

Friends or Foes: Fundamental Principles of Th-Organic Scaffold Chemistry Using Zr-Analogs as a Guide
Jaewoong Lim - ,
Kyoung Chul Park - ,
Grace C. Thaggard - ,
Yuan Liu - ,
Buddhima K. P. Maldeni Kankanamalage - ,
Donald J. Toler - ,
An T. Ta - ,
Preecha Kittikhunnatham - ,
Mark D. Smith - ,
Simon R. Phillpot - , and
Natalia B. Shustova *
The fundamental interest in actinide chemistry, particularly for the development of thorium-based materials, is experiencing a renaissance owing to the recent and rapidly growing attention to fuel cycle reactors, radiological daughters for nuclear medicine, and efficient nuclear stockpile development. Herein, we uncover fundamental principles of thorium chemistry on the example of Th-based extended structures such as metal–organic frameworks in comparison with the discrete systems and zirconium extended analogs, demonstrating remarkable over two-and-half-year chemical stability of Th-based frameworks as a function of metal node connectivity, amount of defects, and conformational linker rigidity through comprehensive spectroscopic and crystallographic analysis as well as theoretical modeling. Despite exceptional chemical stability, we report the first example of studies focusing on the reactivity of the most chemically stable Th-based frameworks in comparison with the discrete Th-based systems such as metal–organic complexes and a cage, contrasting multicycle recyclability and selectivity (>97%) of the extended structures in comparison with the molecular compounds. Overall, the presented work not only establishes the conceptual foundation for evaluating the capabilities of Th-based materials but also represents a milestone for their multifaceted future and foreshadows their potential to shape the next era of actinide chemistry.

Determination of the Hammett Acidity of HF/Base Reagents
Mélissa Longuet - ,
Kassandra Vitse - ,
Agnès Martin-Mingot - ,
Bastien Michelet *- ,
Frédéric Guégan *- , and
Sébastien Thibaudeau *
Harnessing the acidity of HF/base reagents is of paramount importance to improve the efficiency and selectivity of fluorination reactions. Yet, no general method has been reported to evaluate their acidic properties, and experimental designs are still relying on a trial-and-error approach. We report a new method based on 19F NMR spectroscopy which allows highly sensitive measures and short-time analyses. Advantageously, the basic properties of the indicators can be determined upstream by DFT calculations, affording a simple yet robust semiempirical approach. In particular, the indicators used in this study were rationally designed to fit on the conceptually appealing and commonly used Hammett scale. This method has been applied to commercially available and recently developed HF/base reagents.

Methanetriol─Formation of an Impossible Molecule
Joshua H. Marks - ,
Xilin Bai - ,
Anatoliy A. Nikolayev - ,
Qi’ang Gong - ,
Cheng Zhu - ,
N. Fabian Kleimeier - ,
Andrew M. Turner - ,
Santosh K. Singh - ,
Jia Wang - ,
Jiuzhong Yang - ,
Yang Pan - ,
Tao Yang *- ,
Alexander M. Mebel *- , and
Ralf I. Kaiser *
Orthocarboxylic acids─organic molecules carrying three hydroxyl groups at the same carbon atom─have been distinguished as vital reactive intermediates by the atmospheric science and physical (organic) chemistry communities as transients in the atmospheric aerosol cycle. Predicted short lifetimes and their tendency to dehydrate to a carboxylic acid, free orthocarboxylic acids, signify one of the most elusive classes of organic reactive intermediates, with even the simplest representative methanetriol (CH(OH)3)─historically known as orthoformic acid─not previously been detected experimentally. Here, we report the first synthesis of the previously elusive methanetriol molecule in low-temperature mixed methanol (CH3OH) and molecular oxygen (O2) ices subjected to energetic irradiation. Supported by electronic structure calculations, methanetriol was identified in the gas phase upon sublimation via isomer-selective photoionization reflectron time-of-flight mass spectrometry combined with isotopic substitution studies and the detection of photoionization fragments. The first synthesis and detection of methanetriol (CH(OH)3) reveals its gas-phase stability as supported by a significant barrier hindering unimolecular decomposition. These findings progress our fundamental understanding of the chemistry and chemical bonding of methanetriol, hydroxyperoxymethane (CH3OOOH), and hydroxyperoxymethanol (CH2(OH)OOH), which are all prototype molecules in the oxidation chemistry of the atmosphere.

The Mechanism of Rh(I)-Catalyzed Coupling of Benzotriazoles and Allenes Revisited: Substrate Inhibition, Proton Shuttling, and the Role of Cationic vs Neutral Species
Nora Jannsen *- ,
Fabian Reiß - ,
Hans-Joachim Drexler - ,
Katharina Konieczny - ,
Torsten Beweries *- , and
Detlef Heller *
This publication is Open Access under the license indicated. Learn More
Direct coupling of benzotriazole to unsaturated substrates such as allenes represents an atom-efficient method for the construction of biologically and pharmaceutically interesting functional structures. In this work, the mechanism of the N2-selective Rh complex-catalyzed coupling of benzotriazoles to allenes was investigated in depth using a combination of experimental and theoretical techniques. Substrate coordination, inhibition, and catalyst deactivation was probed in reactions of the neutral and cationic catalyst precursors [Rh(μ-Cl)(DPEPhos)]2 and [Rh(DPEPhos)(MeOH)2]+ with benzotriazole and allene, giving coordination, or coupling of the substrates. Formation of a rhodacycle, formed by unprecedented 1,2-coupling of allenes, is responsible for catalyst deactivation. Experimental and computational data suggest that cationic species, formed either by abstraction of the chloride ligand or used directly, are relevant for catalysis. Isomerization of benzotriazole and cleavage of its N–H bond are suggested to occur by counteranion-assisted proton shuttling. This contrasts with a previously proposed scenario in which oxidative N–H addition at Rh is one of the key steps. Based on the mechanistic analysis, the catalytic coupling reaction could be optimized, leading to lower reaction temperature and shorter reaction times compared to the literature.

Regulating Reactive Oxygen Species over M–N–C Single-Atom Catalysts for Potential-Resolved Electrochemiluminescence
Yan Zhou - ,
Yu Wu - ,
Zhen Luo - ,
Ling Ling - ,
Mengzhen Xi - ,
Jingshuai Li - ,
Liuyong Hu *- ,
Canglong Wang - ,
Wenling Gu *- , and
Chengzhou Zhu *
The development of potential-resolved electrochemiluminescence (ECL) systems with dual emitting signals holds great promise for accurate and reliable determination in complex samples. However, the practical application of such systems is hindered by the inevitable mutual interaction and mismatch between different luminophores or coreactants. In this work, for the first time, by precisely tuning the oxygen reduction performance of M–N–C single-atom catalysts (SACs), we present a dual potential-resolved luminol ECL system employing endogenous dissolved O2 as a coreactant. Using advanced in situ monitoring and theoretical calculations, we elucidate the intricate mechanism involving the selective and efficient activation of dissolved O2 through central metal species modulation. This modulation leads to the controlled generation of hydroxyl radical (·OH) and superoxide radical (O2·–), which subsequently trigger cathodic and anodic luminol ECL emission, respectively. The well-designed Cu–N–C SACs, with their moderate oxophilicity, enable the simultaneous generation of ·OH and O2·–, thereby facilitating dual potential-resolved ECL. As a proof of concept, we employed the principal component analysis statistical method to differentiate antibiotics based on the output of the dual-potential ECL signals. This work establishes a new avenue for constructing a potential-resolved ECL platform based on a single luminophore and coreactant through precise regulation of active intermediates.

Axially Chiral Nonbenzenoid Nanographene with Second Harmonic Generation Property
Liyuan Qin - ,
Jin Xie - ,
Botao Wu - ,
Hao Hong - ,
Suyu Yang - ,
Zhuangzhuang Ma - ,
Cheng Li - ,
Guanxin Zhang - ,
Xi-Sha Zhang *- ,
Kaihui Liu - , and
Deqing Zhang *
Chiral nanographenes (NGs) have garnered significant interest as optoelectronic materials in recent years. While helically chiral NGs have been extensively studied, axially chiral NGs have only witnessed limited examples, with no prior reports of axially chiral nonbenzenoid NGs. Herein we report an axially chiral nonbenzenoid nanographene featuring six pentagons and four heptagons. This compound, denoted as 2, was efficiently synthesized via an efficient Pd-catalyzed aryl silane homocoupling reaction. The presence of two bulky 3,5-di-tert-butylphenyl groups around the axis connecting the two nonbenzenoid PAH (AHR) segments endows 2 with atropisomeric chirality and high racemization energy barrier, effectively preventing racemization of both R- and S-enantiomers at room temperature. Optically pure R-2 and S-2 were obtained by chiral HPLC separation, and they exhibit circular dichroism (CD) activity at wavelengths up to 660 nm, one of the longest wavelengths with CD responses reported for the chiral NGs. Interestingly, racemic 2 forms a homoconfiguration π-dimer in the crystal lattice, belonging to the I222 chiral space group. Consequently, this unique structure renders crystals of 2 with a second harmonic generation (SHG) response, distinguishing it from all the reported axially chiral benzenoid NGs. Moreover, R-2 and S-2 also exhibit SHG-CD properties.

Precise Distance Control and Functionality Adjustment of Frustrated Lewis Pairs in Metal–Organic Frameworks
Wenhao Chen - ,
Shenhui Li *- ,
Lezhi Yi - ,
Ziyi Chen - ,
Zihao Li - ,
Yifan Wu - ,
Wei Yan - ,
Feng Deng *- , and
Hexiang Deng *
We report the construction of frustrated Lewis pairs (FLPs) in a metal–organic framework (MOF), where both Lewis acid (LA) and Lewis base (LB) are fixed to the backbone. The anchoring of a tritopic organoboron linker as LA and a monotopic linker as LB to separate metal oxide clusters in a tetrahedron geometry allows for the precise control of distance between them. As the type of monotopic LB linker varies, pyridine, phenol, aniline, and benzyl alcohol, a series of 11 FLPs were constructed to give fixed distances of 7.1, 5.5, 5.4, and 4.8 Å, respectively, revealed by 11B–1H solid-state nuclear magnetic resonance spectroscopy. Keeping LA and LB apart by a fixed distance makes it possible to investigate the electrostatic effect by changing the functional groups in the monotopic LB linker, while the LA counterpart remains unaffected. This approach offers new chemical environments of the active site for FLP-induced catalysis.

Tuning Spin-Polarized Lifetime at High Carrier Density through Deformation Potential in Dion–Jacobson-Phase Perovskites
Yuling Huang - ,
Congcong Chen - ,
Shaokuan Gong - ,
Qiushi Hu - ,
Jingjing Liu - ,
Hongyu Chen - ,
Lingling Mao *- , and
Xihan Chen *
The control of spin relaxation mechanisms is of great importance for spintronics applications as well as for fundamental studies. Layered metal-halide perovskites represent an emerging class of semiconductors with rich optical spin physics, showing potential for spintronic applications. However, a major hurdle arises in layered metal-halide perovskites with strong spin–orbit coupling, where the spin lifetime becomes extremely short due to D’yakonov–Perel’ scattering and Bir–Aronov–Pikus at high carrier density. Using the circularly polarized pump–probe transient reflection technique, we experimentally reveal the important scattering for spin relaxation beyond the electron–hole exchange strength in the Dion–Jacobson (DJ)-type 2D perovskites (3AMP)(MA)n−1PbnI3n+1 [3AMP = 3-(aminomethyl)piperidinium, n = 1–4]. Despite a more than 10-fold increase in carrier concentration, the spin lifetimes for n = 3 and 4 are effectively maintained. We reveal neutral impurity and polar optical phonon scatterings as significant contributors to the momentum relaxation rate. Furthermore, we show that more octahedral distortions induce a larger deformation potential which is reflected on the acoustic phonon properties. Coherent acoustic phonon analysis indicates that the polaronic effect is crucial in achieving control over the scattering mechanism and ensuring spin lifetime protection, highlighting the potential of DJ-phase perovskites for spintronic applications.

Breaking the Activity–Selectivity Trade-off for CH4-to-C2H6 Photoconversion
Kai Zheng - ,
Mingyu Wu - ,
Juncheng Zhu - ,
Wei Zhang - ,
Siying Liu - ,
Xiaojing Zhang - ,
Yang Wu - ,
Li Li - ,
Bangwang Li - ,
Wenxiu Liu - ,
Jun Hu - ,
Chengyuan Liu - ,
Junfa Zhu - ,
Yang Pan - ,
Meng Zhou *- ,
Yongfu Sun *- , and
Yi Xie *
Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity–selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu–1 h–1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h–1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

Catalytic, Spectroscopic, and Theoretical Studies of Fe4S4-Based Coordination Polymers as Heterogenous Coupled Proton–Electron Transfer Mediators for Electrocatalysis
Ningxin Jiang - ,
Andrea Darù - ,
Špela Kunstelj - ,
Jenny G. Vitillo - ,
Maia E. Czaikowski - ,
Alexander S. Filatov - ,
Anna Wuttig - ,
Laura Gagliardi - , and
John S. Anderson *
Iron–sulfur clusters play essential roles in biological systems, and thus synthetic [Fe4S4] clusters have been an area of active research. Recent studies have demonstrated that soluble [Fe4S4] clusters can serve as net H atom transfer mediators, improving the activity and selectivity of a homogeneous Mn CO2 reduction catalyst. Here, we demonstrate that incorporating these [Fe4S4] clusters into a coordination polymer enables heterogeneous H atom transfer from an electrode surface to a Mn complex dissolved in solution. A previously reported solution-processable Fe4S4-based coordination polymer was successfully deposited on the surfaces of different electrodes. The coated electrodes serve as H atom transfer mediators to a soluble Mn CO2 reduction catalyst displaying good product selectivity for formic acid. Furthermore, these electrodes are recyclable with a minimal decrease in activity after multiple catalytic cycles. The heterogenization of the mediator also enables the characterization of solution-phase and electrode surface species separately. Surface enhanced infrared absorption spectroscopy (SEIRAS) reveals spectroscopic signatures for an in situ generated active Mn–H species, providing a more complete mechanistic picture for this system. The active species, reaction mechanism, and the protonation sites on the [Fe4S4] clusters were further confirmed by density functional theory calculations. The observed H atom transfer reactivity of these coordination polymer-coated electrodes motivates additional applications of this composite material in reductive H atom transfer electrocatalysis.
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