ConspectusNear-infrared II (NIR-II, 900-1700 nm) fluorescence imaging is transforming biological visualization, offering deeper, sharper, and more reliable detection than visible or NIR-I probes. Reduced scattering and autofluorescence in this window enable real-time imaging of tissues and organs. Gold nanoclusters (AuNCs) are promising NIR-II agents due to their atomically precise structures, biocompatibility, and versatile surface chemistry. However, their modest photoluminescence (PL) in aqueous environments, which is crucial for biomedical applications, remains a key limitation, making brightness enhancement a central challenge.The Au-ligand interface is critical: small changes in ligand structure or binding can strongly affect electronic relaxation. Smart ligand design, including bidentate thiols, electron-rich groups, or N-heterocyclic carbenes, stabilizes excited states and suppresses nonradiative losses. Beyond ligand optimization, strategies such as protein or polymer encapsulation, controlled self-assembly, and layer-by-layer coatings have increased quantum yields to nearly 10% in the 900-1300 nm range, underscoring the role of the metal-ligand environment.The nano(bio)interface also dictates practical performance. In complex milieus, proteins, redox agents, and pH fluctuations can stabilize or quench emission. Antifouling coatings (zwitterionic ligands, PEGylation, or rigid carbene shells) help preserve brightness, while kernel locking, heteroatom doping, and hybrid constructs with dyes or biomolecules extend emission beyond 1200 nm and enable red-shifting via Förster energy transfer (FRET) or bioluminescence energy transfer (BRET).Bright, stable AuNCs thus serve as both imaging agents and theranostic platforms, combining fluorescence with drug delivery, phototherapy, or radioenhancement. Their deep-tissue sensitivity makes them powerful tools for monitoring cancer, cardiovascular disease, and neuroinflammation. Yet environmental sensitivity also raises challenges: stability, biotransformation, and immune activation highlight the need for standardized evaluation of colloidal stability, photostability, and biological interactions.In this Account, we summarize strategies to boost AuNC brightness in water, including ligand design, molecular assembly, protein/polymer encapsulation, and controlled self-assembly, achieving PL quantum yields up to 10%. We also discuss how pH, redox conditions, protein binding, and intracellular aggregation shape NIR-II emission, highlighting key principles for advancing their biomedical use.

ConspectusThe nano-bio interface, where nanomaterials and biological systems converge, represents a critical frontier in modern science, bridging materials chemistry with biotechnology. A deep understanding of the physicochemical processes at this interface is essential for both assessing the environmental impact of nanomaterials and for designing new bioinspired technologies. While much of this field has focused on bacteria and eukaryotes, the domain of Archaea, pivotal to global biogeochemical cycles and a promising resource for bioenergy, remains a comparatively underexplored territory. The unique cellular architecture of archaea, particularly their distinct membrane lipids and crystalline surface layers (S-layers), presents a unique set of rules for nano-bio interactions, making the study of the nano-archaea interfaces a grand challenge of fundamental importance.In this Account, we summarize the biophysical tools and bioengineering strategies developed in our laboratory to probe and program the nano-archaea interaction. We first developed a single-cell anaerobic atomic force microscopy (AFM) technique to overcome the primary technical barrier of measuring these sensitive, strictly anaerobic organisms , which provided an unprecedented window into the archaeal nanomechanical world. This platform enabled us to reveal the critical role of the archaeal S-layer in maintaining the cellular stability and mediating hydrophobic interactions. We then deciphered the complex chemical dialogue between nanoparticles and archaea, discovering the dominant influence of nanoparticle surface chemistry on the nature of the interaction and the ultimate biological response. Building upon this foundation of fundamental understanding, we have rationally designed and constructed several functional nano-archaeal biohybrid systems. These breakthroughs, progressing from tool development to fundamental discovery and finally to functional engineering, not only help fill a theoretical gap in nanointerface science but also provide new strategies and insights for developing next-generation biotechnologies.

ConspectusThe conversion of solar energy into chemical fuels via photocatalytic water splitting represents a promising pathway to sustainable hydrogen production. Halide perovskites (HPs) have emerged as remarkable photocatalysts owing to their strong visible-light absorption, tunable bandgaps, long carrier diffusion lengths, and defect-tolerant electronic structures. The photocatalytic hydrogen evolution in aqueous solution was first reported in 2016, wherein the inherent aqueous instability of HPs was addressed through a dissolution-precipitation dynamic equilibrium between the halide perovskite (HP) powders and HP-saturated hydroiodic acid (HI) solution. Early systems, however, faced fundamental limitations: (1) limited charge utilization due to the high carrier recombination and insufficient surficial reactive sites; (2) restriction to the hydrogen evolution half-reaction in concentrated HI solution, which was an uneconomical material source and also caused thermodynamic inefficiency for I oxidation instead of water splitting.Over the past decade, our research has focused on addressing these challenges through a combination of material- and system-level innovations. On the materials side, we have explored cocatalyst loading, heterostructure and composite construction, and compositional tuning at the A-, B-, and X-sites to improve carrier utilization efficiency and accelerate surface reaction kinetics, thereby improving photocatalytic performance. These efforts have enabled solar-to-hydrogen (STH) conversion efficiencies exceeding 5% for HI splitting and set the foundation for further advancements. At the system level, we pioneered a solar-driven decoupled water-splitting platform by integrating HP-based photocatalytic hydrogen evolution with spatially separated electrocatalytic or photoelectrocatalytic water oxidation via an I/I redox shuttle. This design resolved critical issues of instability and thermodynamic limitation of HPs for direct water splitting, enabling sustained and stoichiometric hydrogen and oxygen evolution. Building on this, we introduced hydrolytically stable HPs through organic macromolecule incorporation and paired them with complementary oxygen evolution photocatalysts to establish Z-scheme configurations operating in mildly acidic media. Together, these advances in HP-based systems have enabled solar-driven overall water splitting, with STH efficiencies exceeding 2%.This Account summarizes the evolution of HP photocatalysis from early sacrificial hydrohalic acid splitting to integrated solar-driven overall water splitting, highlighting the interplay between material modifications and system designs in overcoming key bottlenecks. We conclude by discussing persistent challenges, including long-term stability, morphology and particle-size control, and interfacial charge management, while outlining future research directions toward translating laboratory advances into practical and scalable solar hydrogen production.

ConspectusPolyaniline, first discovered from coal tar over 150 years ago, is one of the most explored conducting polymers, due to its unique doping/dedoping chemistry, redox behavior, chemical stability, and simple synthesis. About 20 years ago, polyaniline nanofibers were developed through both interfacial polymerization and a rapid mixing method that produced high surface areas and aqueous dispersions, leading to versatile applications. Aniline oligomers, with much shorter and more well-defined chain lengths, gained great attention because they could offer more thorough insights into fundamental properties and perform precise molecular engineering for functionalization and modification. This Account summarizes our recent efforts to probing physical and chemical properties, crystal growth, catalytic effects, and applications of aniline oligomers.With a defined number of doping sites in the phenyl-capped aniline tetramer, we reveal the doping sequence by performing partial doping with characterization using electron paramagnetic resonance. Distinct from polyaniline, aniline tetramers can be dissolved in common organic solvents, thus offering an opportunity to observe the reduction through UV-vis spectroscopy. Acid reductions of the fully oxidized form, known as pernigraniline, were carried out at liquid/liquid and solid/vapor interfaces, as well as by using galvanic and piezoelectric reduction in solid-state reactions. Taking advantage of treating aniline oligomers as small molecules, we demonstrate the growth of organic single crystals through self-assembly. With various acids as dopants, a variety of nanostructured aniline oligomers with well-defined and hierarchical morphologies have been created. Furthermore, by adjustment of the molecule-solvent interactions, organic crystals of the aniline tetramer can be selectively grown on graphene substrates due to strong π-π stacking. The nucleation density, crystal size, and orientation of the organic crystals can be tuned using different solvents and infiltrating nonsolvents in an antisolvent crystallization process, providing an enhanced understanding of directional electrical conductivity in organic crystals. In the aniline polymerization process, it was realized that aniline oligomers serve as both nucleation sites and catalysts to produce ultralong and fibrillar morphologies. Through molecular engineering, the functionalization of the aniline tetramer with perfluorophenyl azide is demonstrated, rendering surface modifications of graphitic materials and antifouling and antibacterial ultrafiltration membranes via a simple UV light exposure. In addition, by covalently grafting aniline oligomers onto reduced graphene oxides and carbon nanotubes as the electrodes, supercapacitors with an ultralong cycle life─5 times longer than their polyaniline composite counterparts─are created. The superior cycling stabilities are due to the successful prevention of detachment of aniline oligomers and the preservation of the microstructure throughout the cycling process.With precise molecular structures and exceptional processability, we have found exciting properties and developed useful applications that outperform their polymer counterparts. Future research on aniline oligomers promises more discoveries of intriguing molecular science properties and practical applications with enhanced performances.

ConspectusThe electrochemical carbon dioxide reduction reaction (eCORR) is a promising technology for reducing carbon emissions and producing valuable multicarbon and nitrogen-containing chemicals from CO. Among these, C products such as ethylene (CH), ethanol (EtOH), acetate (AcO)/acetic acid (AcOH), and urea are of particular interest due to their industrial value. The key to achieving these products lies in controlling C-C and C-N bond coupling, particularly by regulating the adsorption energy and geometry of the reaction intermediates. Compared to single-metal catalysts, multimetal systems offer better control over these intermediates through spatial configurations and adjustable adsorption properties, enabling more selective C-C and C-N coupling. However, achieving high selectivity for the target product remains challenging due to complex interactions among reaction pathways, binding energies, and the dynamic electrochemical environment. To overcome this, it is essential to understand how metal types, metal site arrangements, and coordination environments influence intermediate activation. Metal-organic frameworks (MOFs) offer a unique platform for designing such catalysts due to their structural order and atomic-level tunability. This Account systematically summarizes the structural engineering strategies of multimetal catalysts based on MOFs in the eCORR and categorizes them into three typical types: (1) Multicopper sites, which can promote C-C coupling reactions between *CO and *CHO intermediates and are conducive to the generation of CH; further optimization of the chemical microenvironment can significantly enhance catalytic efficiency. (2) Adjacent heterometal sites based on Cu and oxyphilic metal such as the Cu-Sn site, which display different affinities of distinct metal centers for C and O atoms in the eCORR, achieving C-C coupling between *CO and *OCH intermediates for the production of EtOH. (3) Cooperative Fe-based multimetallic sites, which take advantage of the strong nitrogen affinity of Fe sites and the CO activation ability of Cu/Ni centers to promote selective C-N coupling for urea synthesis. The above structure-performance relationships provide theoretical basis and practical guidance for yielding target C products or urea with high selectivity through eCORR. This Account not only constructs a conceptual framework for the selective synthesis of C compounds and urea starting from CO but also highlights the flexibility and controllability of MOF-based multimetal catalysts as an ideal platform for CO resource utilization and systematically provides guidance for the selective acquisition of specific complex products. Finally, we summarize several key design principles and future development directions, aiming to bridge the gap between a molecular-level understanding and practical device integration. To further enhance performance and deepen understanding of the catalytic mechanism, subsequent research is still needed to develop MOF-based electrocatalysts with more performance multimetallic site configurations and promote their application in industrial-related electrochemical manufacturing.

ConspectusGuanidine exhibits both similarities and differences compared to amines, endowing it with unique catalytic properties. The synthesis of chiral guanidine organocatalysts has garnered significant interest, focusing on three primary guanidine backbones: bicyclic, monocyclic, and open-chain structures. Acyclic guanidines, while more synthetically accessible than their cyclic counterparts, present challenges due to their flexible conformations and multiple substitution patterns. Moreover, the potential of chiral guanidine ligands in metal complex catalysis remains largely underexplored.Our research group has been actively exploring chiral guanidine-amide-based asymmetric catalysis since 2009. The design strategy for these catalysts is rooted in the bifunctional capabilities of amino acids, which are easily functionalized into acyclic guanidine amides. These compounds incorporate new Brønsted base units and hydrogen bond donors. The readily tunable structure of guanidine amides allows five forms, including monoguanidine amide (), bisguanidine and its hemisalt (), guanidine sulfonamide (), hybrid guanidine amide-pyridine (), and quaternary guanidinium salt (). The applications of these compounds in asymmetric catalysis can be driven into four modes based on the role of guanidines: organocatalysis, organo-metal synergistic catalysis, guanidine/transition metal complex catalysis, and phase-transfer catalysis. First, as bifunctional organocatalysts through base/H-bond activation, guanidine derivatives have demonstrated exceptional diastereo- and enantioselectivity in a wide range of reactions including polar addition and cascades, cyclization, substitution, and insertion, etc. In these cases, abundant and labile H-bond interactions from both guanidine and amides account for the high diastereo- and enantioselectivity. Second, the combination of chiral guanidines with achiral dirhodium salts enabled synergistic catalysis to activate the reaction partners simultaneously, where the guanidine unit is disclosed as a proton shuttle or a chalcogen bond acceptor. Third, the copper complexes of guanidine amides and hybrid guanidines could promote both polar and radical reactions. The unique performance of these new catalysts lies in either bifunctional catalysis via a combination of metal coordination and H-bond assistance or rich electronic and coordination properties to leverage the redox ability of the catalytic species. In addition, the quaternary guanidinium salt has emerged as an effective bifunctional phase-transfer catalyst for tackling the challenging enantioselectivity issue in asymmetric α-aromatization of arynes.In this Account, we recount the development of a series of chiral guanidine-amide-based organocatalysts and ligands derived from amino acids. Their applications are meticulously selected from a diverse array of asymmetric reactions, highlighting the evolution of their structures, functionalities, and mechanistic features. Special emphasis is placed on the key factors that contribute to high stereoselectivity in representative catalytic processes.

ConspectusPhotoelectrochemical (PEC) systems are among the most promising solar-to-electrochemical energy conversion and storage technologies and are uniquely positioned to address global energy demand and environmental sustainability. Mimicking the essential functions of natural photosynthesis, including light harvesting, catalytic water oxidation, CO reduction, and energy storage, requires materials that integrate efficient photon capture with rapid charge transport and robust catalytic activity. However, conventional photoelectrochemical materials are limited by the incomplete utilization of the solar spectrum and rapid charge recombination, leading to a narrowed redox potential window and compromised overall conversion efficiency. In this context, organic molecular PEC materials offer distinct advantages through their tunable, well-defined structures, enabling precise control over their electronic properties, redox behavior, and broad-spectrum light utilization. Integrating electron donor-acceptor (D-A) frameworks with redox-active or catalytic units into porous assemblies establishes spatially organized pathways for charge separation and catalytic transformation, although such a molecular-level design remains in its early stages. The central challenge lies in translating these structure-function insights into design principles that deliver multifunctional materials capable of controlled charge modulation, long-range electron transfer, and adaptive catalysis, thereby advancing the realization of complete artificial photosynthesis.In this Account, we begin with decoding PEC systems through the design principles of molecular materials, emphasizing how molecular-level modifications influence key performance metrics. The main concept of developing molecular materials through molecular engineering for artificial photosynthesis, centered on PEC energy conversion and storage, is presented in this Account. It focuses on the state-of-the-art construction of efficient D-A structures by tuning functional groups and incorporating single and dual metals, with charge dynamics regulated by thermodynamic and kinetic processes. Advances and challenges in molecular engineering are highlighted, emphasizing that designing efficient D-A architectures requires the appropriate selection of molecular functional groups, tailored structures, and optimized properties, which are crucial for regulating long-lived charge separation states and driving diverse redox reactions in PEC systems. We outline best practices for designing and assembling coupled D-A architectures, highlighting our research contributions and the broader progress in solar-to-electrochemical energy conversion and storage during the past decade. The discussion further explores coupled/decoupled strategies, which offer solutions to challenges associated with solar-driven CO splitting (for CO and O generation), N reduction (for NH synthesis), and organic molecular-level energy storage devices (solar batteries), and is extended to perspectives on sustainable development. Taken together, we anticipate that this Account will outline emerging strategies for integrating multifunctionality into PEC molecular assemblies, providing valuable design insights for adaptable materials that enhance solar-to-electrochemical energy conversion and storage efficiency.

ConspectusReactive intermediates are valuable and intriguing in synthetic chemistry, but their high reactivity often makes them challenging to handle. Therefore, developing strategies to generate these species in a mild and controlled manner is crucial. One effective approach involves embedding the reactive intermediate within a molecular scaffold. Upon gentle heating, the scaffold undergoes fragmentation, liberating the desired intermediate. Ideally, the resulting byproducts are inert and do not participate in the subsequent reaction. Carpino's hydrazine, HN ( = CH or anthracene), thus serves as an excellent scaffold candidate. By attaching a functional group of interest (E) to the hydrazine, the resulting compound EN is expected to undergo fragmentation, releasing E, dinitrogen (N), and anthracene.In this account, we describe our efforts to develop a series of molecular precursors featuring the composition EN (E = C, CH, SO, RLB, and RB). These precursors are expected to be capable of releasing a single carbon atom, methylene, sulfur monoxide, borylene, and boryl anion, respectively. Interestingly, the fragmentation behavior of these hydrazine-based precursors is highly dependent on the substituents at nitrogen. For CN, HCN, and OSN, the precursors are stable at room temperature. Meanwhile, for (RLB)N, and (RB)N, the precursors are transient intermediate and undergo anthracene extrusion even at low temperatures.While the initial goal was to generate reactive species E, many cases have shown that free intermediates are not necessarily required for group transfer reactions. Instead, the hydrazine precursors often facilitate group transfer through highly selective, associative mechanisms (Type A). Additionally, the diazo intermediates formed via primary fragmentation are of particular interest, as they display reactivity analogous to diazoalkanes (RCN) or organic azides (RN, Type B). Notably, although hydrazine precursors, diazo intermediates, and low-valent species all participate in group transfer reactions, they exhibit distinct electronic structures. Consequently, their reactivity patterns and selectivity vary significantly, underscoring the diverse chemical space accessible through this versatile platform.We believe that continued development of Carpino's hydrazine derivatives holds significant potential for uncovering new reactive intermediates and gaining deeper mechanistic insights. Moreover, the reactivity demonstrated with boron may be extended to other main group elements, potentially enabling access to a broader class of compounds featuring terminal N complexes.

ConspectusThe production of value-added chemicals from CO has been a thriving topic of research for the past few decades because of its contribution to a circular carbon economy. Combined with CO capture and storage, thermocatalytic hydrogenation of CO to CHOH with green or blue hydrogen, offers an attractive route to mitigate CO emissions and to decarbonize the chemical industry. Numerous studies have been focused on catalysts based on supported metallic nanoparticles; these catalysts consist of at least one transition or coinage metal and a promoter element combined with an oxide support to disperse the active phase. Besides Zn-promoters used in Cu-based hydrogenation catalysts, numerous reports point to Ga as a promoter for methanol synthesis. In recent years, Ga has been shown to convert almost all transition metals toward selective methanol synthesis, but its specific role remains a topic of discussions.In this Account, we summarize how surface organometallic chemistry (SOMC) has enabled the discovery of novel catalysts and the development of detailed structure-activity relationships. Particularly, we show that Ga uniquely generates alloys with transition and coinage (Cu) metal elements across groups 8-11 and converts them into selective methanol synthesis catalysts. Specifically, we highlight the role of M-Ga alloy formation, alloy stability, and the formation of M(Ga)-GaO interfaces under reaction conditions. This has been possible thanks to the combination of SOMC, which enables the formation of supported nanoparticles with tailored compositions and interfaces, and state-of-the-art characterization including techniques along with computational modeling, including molecular dynamic calculations. Dynamic alloying-dealloying behaviors under reaction conditions and the formation of M/MGa-GaO interfaces are identified as key drivers for efficient methanol formation.

ConspectusContinuous monitoring of physiologically relevant analytes remains an unmet need of high interest to the medical community. Complex biological environments, slow-release affinity receptors, and short sensor lifetimes are just some of the many challenges that stand in the way of delivering real-time analysis for disease diagnosis, prevention, and treatment. Electrochemical biomolecular sensors are poised to address many of these challenges, given their demonstrated ability to detect a wide range of analytes, from proteins to small molecules, in various in vivo applications. Our laboratory has a strong interest in developing electrochemical biomolecular sensors for long-term continuous health monitoring with the ultimate goal of achieving a universal sensing platform.In this Account, we summarize our group's efforts to develop a universal, reagentless continuous monitoring platform for a multitude of biologically relevant targets. We first introduced the molecular pendulum (MP) sensing approach in 2021, which enabled the detection of a variety of essential protein analytes in their physiologically relevant ranges. In subsequent work, we have addressed some limitations to MP universality, first by expanding the analyte scope to include viral particles and electroactive small molecules. We further demonstrated that the MP platform could be integrated with a variety of target receptors, including antibodies, nanobodies, and aptamers, further expanding the receptor space and analyte range of this platform. To address one of the most significant challenges facing the biomolecular sensing community─the inability to overcome strong receptor binding and continuously monitor analytes─we developed an active-reset method for the MP, enabling the continuous detection of proteins through oscillatory receptor regeneration. To integrate sensors into bioelectronic interfaces, we have demonstrated MP function in various microneedle platforms capable of interstitial fluid sampling and monitoring. This platform enabled our laboratory to begin performing a wide range of in vivo tests, as we look forward to new implantable and wearable form factors. Combining all the above factors, we have started to utilize our MP sensing systems to gain critical insights into physiological mechanisms such as inflammation and circadian rhythm disruption by monitoring molecular fluctuations. Given the success of the MP system in targeting a large variety of analytes with high sensitivity, receptor modularity, and in vivo compatibility, we believe that MP sensing can be expanded further and has high potential to serve as a model for universal biomolecular sensing.

ConspectusAsymmetric catalytic radical reactions represent a powerful yet underexplored strategy for the efficient construction of chiral organic molecules. In this field, we have successfully integrated the advantages of electrosynthesis with chiral Lewis acid catalysis to establish an innovative outer-sphere catalytic mode based on chiral radical intermediates. The chiral Lewis acid catalyst activates carbonyl compounds to generate electron-rich enolate intermediates, thus lowering their oxidation potential while simultaneously generating key catalyst-associated radical intermediates under anodic oxidation. The Lewis acid-promoted electron transfer (LCET) mechanism inherently suppresses noncomplexed radical formation, resulting in minimal racemic background interference. Crucially, since the chiral catalyst is attached to the radical intermediate, the stereoselectivity can be modulated through rational ligand design, thereby achieving highly enantioselective radical transformations. This catalytic system is particularly noteworthy as the chiral catalyst engages in both the electron transfer process and stereoselective control. Based on this electrocatalytic platform, we have explored the reactivity of electrochemically generated chiral radical intermediates with various π-systems, including alkenes, alkynes, allenes, conjugated polyenes, and nitronate anions. These reactions consistently deliver excellent stereoselectivity to underscore the generality of this approach. This remarkable result has motivated us to further expand the scope of this strategy to develop asymmetric oxidative and dehydrogenative coupling reactions. Specifically, employing a nickel-bound α-carbonyl radical as a chiral template, we achieved reactions with diverse transient active intermediates, such as radicals and radical cation intermediates generated under electrochemical conditions. Moreover, a new dual-catalytic electrochemical asymmetric system was developed to enable stereodivergent anodically oxidative homocoupling reactions for the predictable synthesis of all stereoisomers of the target molecule with precise control over both absolute and relative stereochemical configurations. The success of this electrocatalytic system demonstrates the synthetic potential of chiral radical intermediates while simultaneously opening new avenues for their application in the asymmetric and stereodivergent synthesis of complex molecular architectures. These advances establish a robust foundation for the advancement of enantioselective electrochemistry and highlight the considerable potential for broader application in synthetic methodologies.

ConspectusMolecular chirality defines the non-superimposability of three-dimensional molecules onto their mirror images. Due to the often drastically distinct biological effects exhibited by enantiomers, the synthesis of enantiopure small organic molecules remains a topic of persistent research interest. Molecular chirality is commonly divided into point, axial, planar, and helical types based on stereogenic elements. In contrast, inherently chiral molecules form a unique category that lacks these conventional chiral elements. Their chirality results from curvature introduced into a planar structure without a perpendicular symmetry plane in two dimensions. A prominent example of this category is inherently chiral macrocycles (ICMs), which possess chirality solely due to their macrocyclic, nonplanar structure. Conversely, ring-opening of an ICM yields an achiral linear molecule. It is noteworthy that while the synthesis and application of conventional chiral molecules have reached a high degree of sophistication, the chemistry of ICMs remains largely unexplored, primarily due to the significant challenges in obtaining them in highly enantioenriched forms. Resolution of racemic samples using analytical HPLC with columns coated with a chiral stationary phase is the most frequently used method to obtain small amounts of enantiomers.Since the beginning of my independent research career in 2018, driven by my long-standing interest in molecular chirality, our group has engaged in the chemistry of inherently chiral macrocyclic compounds, a research field largely neglected and underexplored by mainstream scientists. From the viewpoint of the structure and the diversity of molecular chirality, it is fascinating to generate a chiral molecular space consisting of almost limitless macrocyclic entities that do not rely on chiral building blocks. Beyond their conceivable applications as conventional chiral compounds, ICMs hold significant potential to offer unique advantages and open new opportunities in areas such as molecular recognition, asymmetric catalysis, and functional materials. Over the past six years, to address the limited availability of highly enantiopure ICMs, we have successfully developed three primary strategies: (1) synthesis of ICMs from linear precursors; (2) desymmetrization of symmetric macrocycles; and (3) dynamic kinetic resolution (DKR) of racemic macrocycles, which enables efficient construction of enantiomerically enriched ICMs. With inherently chiral compounds in hand, we are free to systematically study their structure and properties. We have demonstrated that ICMs provide an extraordinary platform for the fabrication of chiroptical materials and chiral catalysts in supramolecular catalysis. In this Account, we summarize our efforts in exploring the chemistry of ICMs, with a focus on the catalytic enantioselective synthesis, their structural characteristics, the assignment of the absolute configuration, and their unique chiroptical properties and potential applications in supramolecular catalysis. We hope the advancement of synthetic methodology can open doors to the rational design and precise construction of novel ICMs. The easy availability of enantioenriched ICMs could then inspire scientists to explore their applications in chemistry, materials, and life sciences.

ConspectusWhile acyl radicals have been harnessed in synthetic chemistry since their discovery in 1932, their environmental applications remain largely unexplored. Conventional water treatment predominantly utilizes inorganic radicals (OH, SO, H) for their potent redox capabilities. Recent advances in peracetic acid (PAA)-based advanced oxidation processes (AOPs) have spotlighted the peroxyacetyl radical (AcOO), an oxidative derivative of the acetyl radical (Ac). Though PAA activation cannot directly generate Ac, the untapped capabilities of Ac merit dedicated investigation.Our work bridges this knowledge gap by establishing low-molecular-weight diketones (LDKs) as tunable precursors for targeted Ac generation. Through integrated electron paramagnetic resonance, laser flash photolysis, and mass spectrometry, we tracked the generation of Ac and its key derivatives─Ac(OH) and AcOO─in UV/LDK systems. Crucially, dissolved oxygen (O) serves as a molecular switch: under oxic conditions, Ac reacts barrier-free with O to form oxidative AcOO, whereas reductive species (Ac and Ac(OH)) dominate under anoxic conditions. This O-dependent speciation creates a unique dual-reactivity platform. Ac and its derivatives exhibit moderate yet selective reduction potentials, enabling tailored applications─from precision pollutant degradation and metal resource recovery to point-of-use disinfection─all controlled solely by O modulation without additional chemicals.By unifying mechanistic insights with environmental innovation, this establishes acyl radicals as a transformative paradigm for advanced redox technologies. We invite chemists to expand radical selection criteria beyond conventional oxidants, prioritizing tunable, selective, and operationally simple systems enabled by Ac chemistry. Key priorities to advance this field include: (1) establishing systematic frameworks for reaction pathways, kinetics, and structure-reactivity relationships across Ac generating systems; (2) quantifying interconversion dynamics among Ac, Ac(OH), and AcOO through combined computational and experimental approaches; and (3) investigating radical acetylation mechanisms and targeted biomolecule modification.

ConspectusThe rapid expansion of the global polymer industry has highlighted the urgent need for sustainable alternatives to traditional synthetic polymers, which are predominantly derived from nonrenewable fossil resources and pose significant environmental challenges due to their persistence in ecosystems. In response, the development of chemically recyclable polymers has emerged as a promising strategy to reconcile the utility of polymer materials with the imperative of sustainability. However, the synthesis of such polymers often faces limitations in monomer diversity, polymerization efficiency, and the ability to achieve true chemical recyclability.In this Account, we present a comprehensive overview of our recent advancements in the synthesis of chemically recyclable polyesters through the alternating copolymerization of aldehydes (or their derivatives) with cyclic anhydrides. This approach leverages abundant and cost-effective feedstocks, including aldehydes derived from renewable resources and cyclic anhydrides prepared from biorenewable diacids, to create a versatile platform for sustainable polymer synthesis. By employing a wide range of monomers, we have successfully synthesized over 140 polyesters with highly tunable structures and properties.A key feature of this copolymerization is its chemical reversibility, a thermodynamic characteristic arising from a low reaction enthalpy change. This results in a ceiling temperature behavior, wherein the polymer becomes unstable with respect to its monomers upon heating. This chemical reversibility is the fundamental principle that enables the efficient, closed-loop chemical recycling that we demonstrate. Additionally, the water-degradable properties of certain copolymers, particularly those derived from formaldehyde, offer a pathway for developing polymers that can fully degrade into valuable small molecules in water or seawater. This feature is particularly significant in the context of marine pollution, where traditional plastics persist for centuries. Furthermore, the polyesters derived from Schiff bases exhibited unique self- and autodegradation properties. This tunable degradation behavior, governed by polymer structure, provides a versatile tool for designing materials with tailored life spans. Moreover, the mechanical and flame-retardant properties of polyesters derived from chloral and cyclic anhydrides make them promising alternatives to conventional poly(vinyl chloride).The broader implications of these studies extend beyond the synthesis of sustainable polyesters. By demonstrating the feasibility of utilizing renewable resources for polymer production, we contribute to the development of a circular economy, where materials are designed with their end-of-life considerations in mind. Future research will focus on expanding the scope of monomers, optimizing polymerization conditions, and integrating these materials into industrial processes.

ConspectusAs a typical class of mechanically interlocked molecules (MIMs), rotaxanes reveal unique interlocked structures, as well as controllable dynamic behaviors that originate from the mechanical bonds. Owing to such attractive structural and dynamic features, rotaxanes have proven to be not only privileged candidates for the construction of diverse artificial molecular machines such as molecular shuttles, molecular muscles, and molecular pumps but also versatile platforms for wide applications in sensing, drug delivery, and catalysis. In particular, aiming at the construction of novel rotaxanes with intriguing (chir)optical properties, the rapid development of luminescent rotaxanes, particularly ones with attractive circularly polarized luminescence (CPL), has been witnessed. On the one hand, the unique interlocked structures of rotaxanes enable the facile introduction of various luminogens into different components with well-defined and tunable chiral arrangements. This makes the resultant integrated luminescent rotaxanes not only attractive candidates for the development of novel CPL-active materials with desirable and tunable CPL performances but also promising platforms for investigations of structure-property relationships. On the other hand, the controllable dynamic features of rotaxanes could lead to the successful construction of novel smart chiral luminescent materials with precisely switchable CPL emission states, including the handedness, emission wavelength, photoluminescence quantum yield (PLQY), and dissymmetry factor (). This further extends their applications in diverse fields, such as smart devices and sensors. Considering all the above broad potential applications, the design and construction of novel CPL-active rotaxanes, particularly ones with tunable and switchable CPL performances, are of great importance.During recent years, through the rational design and synthesis of chiral rotaxanes with precisely arranged luminogens, we realized the successful synthesis of a series of CPL-active rotaxanes. We first confirmed the unique role of mechanical bonds in boosting the CPL performance of chiral pillar[5]arene wheels upon the formation of rotaxanes, highlighting that rotaxanes can serve as promising platforms for the design and construction of novel CPL emitters. Furthermore, through the rational design and synthesis of mechano-stereoisomers, including both static and dynamic ones, the precise tuning and switching of the CPL performances of diverse chiral rotaxanes were successfully realized. In addition to individual chiral rotaxanes, we also showed an interesting generation-dependent CPL performance of rotaxane-branched dendrimers with multiple chiral rotaxane units as branches and realized further enhancement of their CPL performances through sequential light harvesting. In this Account, we summarize our above exploration of rotaxanes with tunable and switchable CPL performances, and we hope that it will inspire scientists from various disciplines to explore these appealing and versatile platforms for wide applications.

ConspectusTailored magnetic nanoparticles (MNPs) have emerged as powerful tools in biomedical imaging, offering enhanced sensitivity, specificity, spatial resolution, and multifunctionality. Their unique physicochemical properties also open promising avenues for therapeutic applications. Continued innovation in MNP design is critical to fully exploit advanced imaging platforms─including high-field magnetic resonance imaging (MRI), magnetic particle imaging (MPI), and multimodal imaging systems─for early diagnosis and precision therapy. However, conventional strategies centered on tuning particle size, shape, composition, and crystallinity offer only limited control over intrinsic microscopic parameters such as magnetic moment orientation, defect structure, and electronic activity, which fundamentally govern imaging performance. This limitation has created a persistent bottleneck in the development of high-performance MNPs. Assembly driven chemical design offers a multiscale design paradigm that spans atomic, interfacial, and nanoscale levels. By inducing emergent collective behaviors not present in individual building blocks, this strategy significantly broadens the design space for optimizing MNP functionality.In this Account, we summarize our recent advances in the assembly driven chemical design of MNPs and their biomedical applications. At the atomic scale, controlled atomic rearrangements, defect engineering, and surface atom segregation are harnessed to fine-tune magnetic moment alignment, magnetic susceptibility, water exchange kinetics, and catalytic activity. At the interfacial level, the assembly of core-shell and organic-inorganic hybrid structures modulates exchange coupling interactions, enabling integrated diagnostic and therapeutic capabilities. At the nanoscale, ligand-mediated MNP assembly imparts stimuli responsiveness and facilitates the integration of multimodal imaging functions. These multiscale design strategies collectively establish robust structure-activity relationships and allow precise tailoring of MNPs for specific biomedical imaging modalities and therapeutic outcomes.We then highlight key breakthroughs enabled by these MNP assemblies. In advanced magnetic imaging, they overcome longstanding limitations in sensitivity and resolution, achieving an ultralow transverse-to-longitudinal relaxivity ratio and enhanced -weighted contrast under high-field MRI, as well as submillimeter spatial resolution in MPI. These performance gains extend the imaging frontier to previously undetectable targets, such as isolated tumor cells as small as ∼0.16 mm, and enable real-time molecular imaging of neuronal signaling in vivo, paving the way for early diagnosis and imaging-guided therapy of malignancies and neurological diseases. Beyond imaging, atomic-scale reconfiguration enables MNPs to structurally mimic the active site architecture of metabolic enzymes such as xanthine oxidoreductase, thereby enabling tumor-selective metabolic therapy.Together, these findings underscore the transformative potential of assembly driven MNP design in next-generation biomedical imaging and precision medicine. We conclude by outlining future directions for constructing life-inspired, multiscale "transformative magnetic artificial molecules," to enable precise sensing and regulation of complex biological activities. Ultimately, assembly driven chemistry offers a robust and versatile framework for the rational development of high-performance MNPs, accelerating their clinical translation and inspiring new therapeutic innovations.

ConspectusReducing bulk crystals to single-unit chains generally yields unique structures and properties, such as the simplest periodicity, high surface-to-volume ratios, and quantum confinement effects, but their synthesis and stabilization under working conditions remain challenging. Single-walled carbon nanotubes (SWCNTs), with well-defined 1-2 nm channels, provide an ideal platform for confined synthesis and studying atomic-scale molecular transport. Additionally, the conductive single-atomic-layer graphene enables the transmission of properties of substances across monolayer graphene, thus enabling surface property modulation and application. Solution-phase confined assembly in SWCNTs presents a versatile alternative to high-temperature vapor transport that is applicable only when the guests are thermally stable and sublimated, although it is rarely achieved. Unveiling molecular transport at the nanoscale is crucial for an in-depth understanding of the driving forces for assembly and, in turn, controlling confined crystallization of metastable crystals with tailored properties. This Account summarizes our recent progress in liquid-phase confined assembly: (i) assembly methodology and mechanistic insights; (ii) controlled synthesis of one-dimensional (1D) metastable crystals and chains; (iii) emerging properties and applications of single-unit-cell chains. In the end, we summarize the present achievements and future challenges.We employ SWCNTs and atomically precise clusters as models to study liquid-phase confined assembly and its mechanism from a real-space perspective. We developed a scalable solution-phase strategy for assembling diverse clusters within SWCNTs, irrespective of their electronic properties or solubility, which was driven by nanoconfinement and electrostatic interactions. Advanced electron microscopy combined with synchrotron X-ray absorption spectroscopy revealed close-packed ordered single-cluster chains, rather than disordered aggregates, within SWCNTs. Inspired by the confined assembly phenomena, we demonstrated efficient capture of heavy elements, including uranium and iodine, within SWCNTs in liquids, with iodine forming ordered single-atom chains. Confined assembly also facilitated the synthesis of 1D crystals with a finite unit-cell thickness and metastable structures. We developed a SWCNT-enabled two-solvent-phase extraction strategy to synthesize single-unit-cell perovskite chains. The resulting chains exhibited unconventional stoichiometries (e.g., [CsPbI]) due to dimensionality reduction, stabilized by charge balance with SWCNT, thus forming strong "cation-π" interactions. These single-unit-cell perovskites within the SWCNT exhibited exceptional performance in X-ray detectors due to suppressed ion migration. SWCNT-confined ordered single-unit-chain catalysts, including single-cluster and single-atom chains, with well-defined structures showed enhanced activity in redox and coupling reactions compared to their isolated counterparts. These identical single-unit chains maintained intimate contact with the conductive monolayer graphene of SWCNTs, enabling charge delocalization on the nanotube surfaces and therefore increasing the density of active sites and reducing activation barriers. These nanotube-confined single-unit chains demonstrated outstanding structural and operational stability. Our atomic-scale insights into confined assembly advance the design of 1D heterostructures with tailored functionalities and deepen the understanding of the structure-activity relationship.

ConspectusEmulsions formed by dispersing one liquid into another immiscible liquid have been a cornerstone of colloid science for over a century. Conventional emulsions are stabilized by surfactants, which reduce interfacial tension from the range of 30-50 mN/m to 1-10 mN/m, allowing droplets to persist against coalescence. Despite their broad industrial relevance, these systems are fundamentally constrained by their interfacial nature: high-energy input is required to generate small, uniform droplets; surfactants may alter physicochemical properties and introduce toxicity; and droplet morphology is largely restricted to isotropic, spherical shapes. Moreover, Ostwald ripening and droplet coalescence, driven by Laplace pressure differences, inevitably lead to thermodynamic instability. These constraints underscore the need for new emulsification paradigms beyond the classical surfactant-stabilized model.Transient emulsions are based on partially miscible liquid pairs such as water and 1-butanol. In these systems, mutual diffusion at the droplet interface generates a blurred transition miscible layer rather than a sharp phase boundary. As a consequence, interfacial tension approaches zero, fundamentally altering the behavior of emulsified droplets and imparting distinctive features: (i) ultrashort lifetime, (ii) absence of surfactants, and (iii) spontaneous emulsification under weak energy perturbation. Notably, the lack of strong interfacial constraints enables transient emulsions to undergo asymmetric deformations that are inaccessible to conventional emulsions.These unique properties open up a new frontier for dynamic, out-of-equilibrium processes, particularly in the self-assembly of colloidal nanoparticles. Transient emulsions offer a versatile platform for constructing colloidal superstructures that would otherwise be unattainable. Three key advances have been demonstrated: , enabling plasmonic superstructures to form within seconds; , achieved through template-confined emulsification; and , facilitated by new hollowing mechanisms in transient aerosol emulsions. Together, these advances establish transient emulsions as a unique vehicle for controlling structure, symmetry, and dynamics in colloidal assemblies.Beyond fundamental insights, transient emulsions have enabled the development of superstructures with new functionalities and applications. Gold microsphere arrays fabricated by emulsion-directed assembly combined with nanosecond laser irradiation enable ultrastable anisotropic conductive bonding, offering a compelling alternative to conventional metal-polymer core-shell microspheres for anisotropic conductive films in micro-LED packaging. Silica-based hemispherical superstructures function as detachable microlenses with tunable magnification, enhancing numerical aperture and photon throughput in optical microscopy. Meanwhile, coatings assembled from concave-convex silica superstructures exhibit exceptional optical diffusion, combining low haze with high brightness for next-generation display and photonic technologies.In short, transient emulsions introduce a new paradigm in colloid and interface science. By removing the constraints of interfacial tension, they open up powerful pathways for dynamic colloidal self-assembly and functional material creation. Going forward, diversifying transient emulsion systems, enhancing structural stability, and developing high-resolution emulsion printing methods could further establish this versatile, efficient, and adaptable platform for engineering complex superstructures, connecting fundamental colloid science with advanced photonic and electronic technologies.

ConspectusCovalent chemical labeling of proteins is central to chemical biology, offering functional modifications beyond imaging probes. While genetically engineered systems using self-labeling tags (e.g., HaloTag, SNAP-Tag) or genetic code expansion have enabled selective labeling in live cells, endogenous (naturally occurring) proteins remain difficult targets because genetic manipulation conferring selectivity cannot be conducted. To address this, ligand-directed chemistry (LDchem) was developed in which labeling reagents combine a ligand, a probe, and a cleavable electrophile. Ligand binding forms a transient complex that guides selective covalent modification, while preserving native protein function. A key feature of LDchem is the proximity effect, where reactivity is spatially restricted to residues adjacent to the ligand-binding site. Surprisingly, the proximity in LDchem often induces accelerated reactions and unexpected modifications such as ether or ester bond formation under mild physiological (aqueous) conditions. Such proximity effects include both local concentration (ligand affinity for concentrating reagents) and orientation (linker length and rigidity for impacting residue selectivity). Studies comparing electrophiles demonstrated reaction rates spanning 4 orders of magnitude, in some cases rivaling those of self-labeling enzyme tags or even fast click reactions. Notably, weaker intrinsic electrophiles can still yield efficient labeling when favorable orientation effects prolong the residential time of reactive groups near target residues. Proximity has also been exploited for protein functionalization. For example, tethering F-NMR probes to carbonic anhydrase converted in-cell to F-NMR biosensors that reported their ligand binding under native conditions. Similarly, attaching fluorescent dyes to receptors allowed evaluation of ligand binding kinetics by live-cell imaging. Recent advances extend LDchem into systems, notably, the live mouse brain. Injection of LDchem reagents into cerebrospinal fluid enabled selective receptor labeling across whole-brain scales visualized with tissue clearing technology. Furthermore, LDchem modified endogenous receptors with a photosensitizer to develop PhoxID, a photoproximity labeling method. In live brains, this enabled proteomic mapping of receptor interactomes with 1-10 min temporal resolution, unveiling developmental shifts in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-associated proximal proteins. LDchem has also been adapted for sensing the vicinity of a target receptor. For instance, AMPARs were converted into fluorescent biosensors to detect matrix metalloproteinase MMP-9 activity in the receptor proximity within ∼10 nm, revealing region-specific and synapse-localized enzymatic activity in the brain. In conclusion, LDchem highlights how proximity effects can be harnessed to achieve selective, accelerated, and functional protein labeling under native biological conditions. Although precise prediction of proximity effects remains challenging due to complex local environments of a target protein, advances in artificial-intelligence-guided computational modeling promise rational design of labeling reagents. Such chemical tools are expected to transform chemical biology, enabling precise interrogation of protein microenvironments and the networks in the whole living systems.

ConspectusAberrant gene expression is frequently linked to the progression of various disorders and diseases, playing an instrumental role in pathological processes. Gene-regulation-related proteins, especially epigenetic enzymes and transcription factors, are critically involved in gene expression patterns. Therefore, targeting endogenous gene regulators presents novel approaches for potential therapeutic intervention.Transition metal complexes have been extensively employed in diagnosis and treatment due to their distinctive properties. Organometallic iridium(III) and rhodium(III) complexes exhibit diverse structures, including photochemical and photophysical properties, kinetic stability, and the ability to interact specifically with biomolecules, particularly DNA and proteins, due to their selective steric engagement. Therefore, octahedral iridium(III) and rhodium(III) complexes represent attractive scaffolds for the design of probes and modulators of gene regulation.Considering the complexity and spatiotemporal specificity of gene regulation, it is crucial to comprehend the interactions between target biomolecules, particularly protein-protein interactions (PPIs), to selectively modulate gene expression patterns. PPIs serve as hubs of cellular signaling flow during most biological activities, including gene expression processes. For example, regulators of histone modifications and transcription factors converge at transcription start sites (TSSs), where they engage unmodified substrates and assemble into transcriptional complexes. Discovering and regulating disease-related abnormal gene expression by modulating pivotal PPIs thus hold great promise. By leveraging their precisely defined steric scaffolds, organometallic iridium(III) and rhodium(III) complexes present a distinctive option for unveiling the biological roles of these proteins and identifying potential modulators.In this Account, we discuss our recent work on discovering organometallic iridium(III) and rhodium(III) complexes for PPI-based gene modulation. First, we describe the interactions between these complexes and transcriptional-regulation-related proteins, including transcription factors and epigenetic enzymes, and discuss the key influences of the ligands and metal center on bioactivity. Second, we describe transition-metal-based conjugates that indirectly interact with gene regulators. Using the conjugation strategy, effective gene modulators can be developed without requiring extensive screening or compromising the ligand's biological activity. Interestingly, modification of the iridium(III) complex may transform the activity from agonistic to antagonistic, offering new insights into the development of gene regulation modulators. Additionally, these conjugates can serve as effective probes for screening gene regulation modulators with the use of time-resolved measurements to minimize interference from fluorescent molecules.In summary, the studies discussed in this Account describe a series of organometallic iridium(III) and rhodium(III) complexes that specifically bind to gene regulatory proteins. These complexes act through precise three-dimensional binding instead of via redox modulation or covalent interactions. We expect that these complexes could provide the basis for the development of organometallic iridium(III)- and rhodium(III)-based drugs and advance our understanding of activity-based gene regulation.

ConspectusLiquid environments play a crucial role in the biological processes occurring in living organisms as well as in many human-made processes involving electrochemistry, photo-, and thermocatalysis. In the majority of these systems, aqueous phases are ubiquitous due to water's natural abundance. Water molecules, however, can exert large changes in the chemical environment of catalytically active sites, altering the reaction rates, selectivity, and catalyst stability. These solvation effects induced by water molecules near catalytic sites can drastically change the energy landscape and unlock unique reaction pathways with far more favorable kinetics. In nature, living organisms couple these complex interactions with detection, communication, and actuation mechanisms to induce self-regulatory behavior, ensuring stability of the system and thus long-term durability. Extrapolating this behavior to heterogeneous catalysis is desirable because the resulting "smart materials" can potentially unlock new chemical conversion processes with higher atom efficiency, rates, and stability.The combination of polymer chemistry and heterogeneous catalysis has introduced versatile approaches for creating materials that can respond to cues in the reaction medium that alter the accessibility, intrinsic activity, and selectivity of the catalyst. To achieve this, one could combine stimulus-responsive polymers, which undergo a large volumetric phase transition in response to an external stimulus, with a solid catalyst. This chemo-mechanical response has been employed to create a variety of nanoreactor vessels with stimulus-responsive character that turn on- and off- depending on the reaction conditions. In this Account, we focus on the impact of these polymer coatings on the solvation environment around the active site and the implications of these effects on the reaction energy landscape, molecular arrangement of the solvent, electric fields at the catalyst-liquid interface, binding energy, and mobility of surface reaction intermediates. These seemingly subtle changes in solvent molecules induced by the presence of polymers can have a tremendous impact on the development of bioinspired heterogeneous catalysts, reliable chemical clocks, micro/nanoreactors, and robots. The large library of polymer chemistries offers a plethora of combinations of stimulus-responsive mechanisms (e.g., temperature, pH, light, magnetic field, solvent composition), providing the possibility of creating homeostatic catalysts .