Accounts of Chemical Research最新文献

By tapping Earth’s most abundant water resource, seawater electrolysis offers a promising route to hydrogen production while reducing reliance on freshwater. However, in natural seawater and at industrial current densities (j), complex ion–catalyst interactions at the interface can accelerate activity decay and undermine long-term durability. On the anode, halide attack dominated by Cl^– can shift selectivity from the oxygen evolution reaction toward the chlorine evolution reaction and trigger the metal-chloride/hydroxide corrosion pathway, causing loss of active sites and poor oxygen selectivity. On the cathode, the local pH increase induced by the hydrogen evolution reaction can drive Mg²⁺/Ca²⁺ precipitation, forming fouling layers that block active sites and hinder continuous operation. Additionally, inadequate control of gas release and the solid–gas interface at industrial j can accelerate bubble-induced mechanical damage to the catalyst layer. In this Account, we summarize our group’s progress in engineering catalyst surfaces and interfaces toward efficient and durable seawater electrolysis.

We begin by outlining anode-focused strategies that improve seawater oxidation activity and halide tolerance. First, anion-species regulation is applied to (1) construct anion-rich surfaces that repel Cl^–, (2) engineer a Lewis-acid-enabled OH^–-enriched microenvironment that favors *OH over Cl^–, and (3) build a high-density negatively charged network that efficiently excludes Cl^– at industrial j. Next, surface coordination regulation is introduced in which strongly chemisorbed molecular regulator tunes the electronic structure of metal centers and reinforces Cl^– repulsion. Subsequently, we design a multidefense architecture that integrates an anion-rich surface and oxygen-intermediate-rich layer within a tip-connected bubble management framework, enabling simultaneous mitigation of chlorine chemistry and mechanical stress at industrial j. On the cathode side, we develop a microscopic bubble/precipitate traffic system (MBPTS) and self-cleaning electrode that control gas and ion transport, continuously remove Mg²⁺/Ca²⁺ deposits, and enable concurrent H₂ production and magnesium recovery. Finally, we outline the remaining limitations and emerging opportunities in seawater electrolysis to inspire next-generation designs for saline electrochemical energy systems and beyond.

Twisted graphene nanoribbons (tw-GNRs), exemplified by helical perylene diimide (hPDI) oligomers and polymers, represent a versatile platform for next-generation organic electronics. Their distinctive architecture features a fused, twisted backbone that simultaneously introduces void space for ion transport while maintaining high electronic conductivity along the graphitic core. This Account details the development of these materials, underpinned by a defect-free polymerization-cyclization synthesis based on perylene tetraester precursors. This robust synthetic route enables the creation of ribbons up to 120 nm long with precise control over molecular length, edge chemistry, and backbone helicity, allowing for a systematic investigation of structure–property relationships.

Leveraging this unique combination of properties, we address key challenges in energy storage, bioelectronics, and chiroptics. In the context of energy storage, we discuss how intermediate-length ribbons strike a structural “sweet spot” that balances the trade-off between electrode insolubility and ion permeability, facilitating ultrafast charging kinetics in lithium and magnesium batteries. Furthermore, we demonstrate how introducing cruciform hinges into the backbone creates an amorphous morphology that resolves the critical “conductivity–hydrophilicity–insolubility” trade-off, enabling high-performance aqueous sodium-ion batteries. In bioelectronics, we describe how modifying the ribbon edges with hydrophilic chains enables high performance and ultrastable n-type organic mixed ionic–electronic conductors (OMIECs) capable of high-fidelity neural recording. Finally, we explore the chiroptical properties of these ribbons, explaining how remote chiral side chains can dynamically induce long-range helical order in the backbone. This structural control allows the materials to function as room-temperature spin filters via the chiral-induced spin selectivity (CISS) effect.

Collectively, these studies illustrate how precise molecular engineering can unlock new functionalities, ranging from dual ion-electron conduction to spin-selective transport, defining a versatile platform for next-generation organic electronics.

Chemokines and their receptors are central regulators of leukocyte trafficking in both physiological immune surveillance and pathological inflammation. In chronic inflammatory diseases such as atherosclerosis, pulmonary fibrosis, rheumatoid arthritis, autoimmune disorders and cancer, dysregulated chemokine networks drive persistent and damaging immune cell infiltration. Given this central role, the chemokine system represents an attractive target for therapeutic intervention. However, despite decades of effort and substantial investment, most clinical trials targeting individual chemokines or chemokine receptors have failed to demonstrate clinical efficacy. A major limitation of the single-target approach lies in the redundancy and complexity of the chemokine network: multiple chemokines are often upregulated simultaneously in disease, each capable of activating overlapping but distinct receptor sets.

Our laboratory’s research focuses on discovering and engineering agents that can neutralize groups of functionally related chemokines, thereby blocking their collective pathological effects. Ticks, which must evade host immunity to feed for days, have evolved a powerful biological solution to target multiple chemokines. They secrete salivary proteins known as “evasins” that bind to and inhibit multiple chemokines. These small proteins offer a unique opportunity to engineer multichemokine inhibitors tailored to specific inflammatory profiles. In this Account, we describe our efforts to understand the molecular basis of evasin–chemokine recognition and to engineer these proteins into therapeutic scaffolds. Using bioinformatics, structural biology and mutagenesis, we have elucidated the atomic-level mechanisms underlying evasin selectivity, identified novel evasins with distinct chemokine-binding profiles, and developed structure-guided strategies to reprogram their selectivity. This Account also highlights complementary studies by other groups that have designed evasin-inspired peptides and employed in vitro evolution strategies to expand chemokine-binding selectivity.

Together, these advances define the design principles governing multichemokine recognition and highlight how natural scaffolds can be repurposed for therapeutic applications. The engineering strategies discussed here also offer a generalizable roadmap for engineering or designing other proteins or peptides with multitarget “specificity”.

Glycosylation is an important biological process for modulating the structure and function of proteins, cells, and many other biologics. Decoding protein glycosylation and glycan–receptor interactions will help us understand the role of post-translational glycosylation with molecular precision and provide new opportunities for developing better glycoprotein medicines to ameliorate diseases associated with aberrant glycosylation. Over the years, we have developed new tools and methods, notably the chemoenzymatic and programmable one-pot methods, for making and studying complex glycans and glycoproteins and investigating the impact of glycosylation on protein folding, viral infection, cancer progression, and immune responses. This Account highlights the advanced glycosylation methods developed in our laboratory to drive new discoveries in glycobiology and accelerate the translation of these discoveries into innovative development. Representative examples include practical and expedient synthesis of oligosaccharides and glycoproteins, development of glycan microarrays, low-sugar universal vaccines with broadly protective immune responses, cell-based production of monoclonal antibodies with humanized Fc-glycosylation optimized to improve efficacy, and common small-molecule blockades targeting multiple Siglec-mediated immune checkpoints. It is anticipated that advances in glycosylation methodology and the extensive data generated over the years, combined with AI-assisted prediction, will lead to a paradigm change in vaccine and antibody development as well as drug discoveries for human health.

Aqueous organic assemblies, including molecular aggregates (MAs), conjugated polymer nanoparticles (PNPs), and their hybrids, have emerged as versatile soft materials for solar light harvesting, photocatalysis, and bioimaging. Such assemblies form through spontaneous self-organization processes, including hydrophobic collapse and multichromophoric packing, resulting in strong interunit coupling and morphology-dependent light–matter interactions. In aqueous environments, hydration shells and structural flexibility further modulate exciton delocalization, energy relaxation, and charge transfer. As a result, both MAs and PNPs exhibit complex excited-state landscapes, featuring bright and dark excitonic states, unconventional relaxation pathways, and long-lived collective excited states, which are distinct from those of the molecules in dilute solution or crystalline films.

Advanced ultrafast spectroscopic techniques are employed to elucidate these excited-state processes, allowing us to correlate morphology, packing, and interunit interactions with exciton localization and delocalization, energy funneling, vibration-mediated relaxation, energy transfer, charge transfer, and charge separation across femtosecond to nanosecond time scales. In MAs, gradual aggregation and controlled structural modification tune exciton delocalization and relaxation, enabling the identification of several dark and bright excitonic manifolds, as well as long-lived charge-separated states in selected aqueous donor–acceptor assemblies. In PNPs, multichromophoric polymer chains confined within hydrated nanoparticles exhibit rapid energy redistribution, stochastic localization, and ultrafast energy funneling into collective excited states that are spatially and energetically distinct from those in MAs or films. These relaxation pathways can be precisely controlled by altering particle size and chromophore density. Analysis reveals the efficient energy and charge transfer processes from these unique excited states, which can be modulated through host–guest interactions and coupling to inorganic nanostructures.

By comparing MAs, PNPs, and their hybrids within a unified spectroscopic framework, this Account highlights how excited-state dynamics evolve as organic chromophores transition from molecules to MAs and ultimately to nanoconfined PNPs, and how their morphology, packing geometry, intermolecular interactions, and interfacial coupling govern excited-state populations and energy flow. Advanced ultrafast spectroscopic methods enable direct correlation between nanoscale structure and excited-state dynamics, offering a design principle for aqueous organic assemblies, in which excited-state dynamics are deliberately engineered for functional photonic, optoelectronic, and light-harvesting applications.

Atomically precise metal nanoclusters (NCs) are a class of nanomaterials composed of a specific number of metal atoms stabilized by well-defined organic ligands. These NCs exhibit molecular-like electronic states and offer exceptional control over their optoelectronic properties. Recent advancements have extended their photoluminescence deep into the near-infrared II (NIR-II) window (950–1700 nm), a spectral region that provides significant advantages for biomedical imaging and photonic applications, including reduced tissue scattering, minimal autofluorescence, and enhanced penetration depth. In comparison to conventional quantum dots and larger plasmonic nanoparticles, atomically precise metal NCs offer unprecedented tunability in terms of emission wavelength, quantum yield, and photostability, facilitated by the modulation of size, composition, and ligand shell chemistry.

In this Account, we highlight cutting-edge strategies, including ligand engineering, core–shell engineering, and alloying, which enable fine-tuning of NIR-II photoluminescence in metal NCs. We also explore the photophysical mechanisms underlying NIR-II emission, such as core–ligand charge transfer, metal-centered transitions, and the role of surface electronic states in radiative recombination efficiency. Advanced spectroscopic techniques, such as time-resolved photoluminescence and transient absorption, are discussed for their ability to probe excited-state lifetimes and energy transfer processes that control the emission properties. Finally, we critically address the current limitations in quantum yield enhancement, long-term photostability, and biocompatibility while outlining future directions for developing hybrid materials and multifunctional NC platforms and advancing NIR-II photonic technologies. Our Account aims to offer molecular-level insights and guide the rational design of next-generation atomically precise metal NCs as versatile materials for advanced NIR-II photoluminescence.

Light in the near-infrared-II (NIR-II, 1000–2500 nm) region has enabled groundbreaking advances in photonic technologies, including long-distance optical communication, deep-tissue optical imaging, noninvasive neuromodulation, and high-efficiency solar energy conversion. Traditional NIR-II-responsive materials, such as rare-earth nanoparticles, carbon nanotubes, quantum dots, and organic chromophores, have achieved important progress. However, their performance is often constrained by intrinsic drawbacks, including narrow spectral response, low quantum yields, toxicity, and/or poor stability.

Recently, atomically precise metal nanoclusters (NCs), which bridge the gap between small molecules (e.g., complexes) and plasmonic nanoparticles, have emerged as a transformative platform for NIR-II photonics. Their tailorable compositions and atomic-level geometric structures give rise to versatile electronic structures, enabling highly controllable NIR-II absorption and emission and precise structure–property correlations. To date, metal NCs have demonstrated superior sensitivity in NIR-II light absorption, broad spectral responsiveness, and high photon-generation efficiency, outperforming many conventional NIR-II materials. These attributes make metal NCs particularly attractive for applications requiring high optical performance, spectral tunability, and biocompatibility.

In this Account, we summarize recent progress in the design, synthesis, and functionalization of NIR-II-responsive metal NCs. We highlight three major design principles that have driven advances in this field: (1) structural anisotropy, which promotes electron delocalization and enhances radiative transitions; (2) heteroatom doping, which modifies electronic transition dipoles and exciton relaxation pathways; (3) ligand engineering, which modulates energy dissipation within NCs and between NCs and their surrounding environment. Together, these approaches offer a versatile framework for controlling NIR-II photon absorption, conversion, and emission at the atomic scale.

Additionally, we discuss emerging applications of NIR-II-active metal NCs in deep-tissue optical bioimaging, photothermal therapy, and photocatalysis. The integration of precise structural control with tunable NIR-II optical properties opens new frontiers for next-generation photonic systems, where light manipulation at the atomic level can translate into transformative advances in biomedicine, sensing, and renewable energy technologies. Looking forward, continued exploration of novel NC structures, dopant chemistry, and surface functionalization will further expand the potential of metal NCs in NIR-II photonics, bridging the gap between fundamental discoveries and real-world applications.

Fibrinogenesis─the transformation of fibrinogen to fibrin─is one of the most significant physiological pathways regulating hemostasis by promoting clot formation at vascular injury sites. Thrombin is the key catalyst driving fibrinogenesis, and thus the control of its activity is of utmost medical significance. While diverse auxiliary therapies exist to regulate blood coagulation and thrombin activity, the temporal, dose-controlled, transient, and periodic control of thrombin and fibrinogenesis remains highly desirable. Antithrombin aptamers─biopolymers that bind to and inhibit thrombin─are ideal for achieving such precise regulation of thrombin activity.

The present Account introduces dynamic DNA networks, machineries, and reaction modules involving antithrombin aptamers for the temporal modulation of thrombin activity. Constitutional dynamic networks (CDNs), dissipative DNA reaction circuits, and dynamic transcription machineries are introduced as functional frameworks to control fibrinogenesis. Phototriggered reconfiguration of CDNs containing thrombin-inhibitory constituents leads to orthogonal dynamic regulatory frameworks, resulting in upregulated or downregulated fibrinogenesis. Coupling CDNs to transient reaction modules generates orthogonal transient upregulation or downregulation of fibrinogenesis. Moreover, transcription machineries are implemented for transient control of fibrinogenesis. This is achieved via the temporal activation and inhibition of thrombin: a transcription machinery transcribes an RNA antidote that displaces the antithrombin DNA aptamer from the thrombin/aptamer complex, while RNase H mediates the dissipative inhibition of thrombin by hydrolytically depleting the RNA antidote in the RNA/DNA aptamer duplex. Additionally, integrating split thrombin aptamers into the phototriggered, oscillatory transcription machinery, in combination with a counter dynamic transcription machinery, guides the transient and oscillatory inhibition of thrombin (via the T7 RNA polymerase/RNase H system). This enables phototriggered transient inhibition and oscillatory modulation of fibrinogenesis, which shows promising potential for spatiotemporal control of blood coagulation. Finally, future perspectives on dynamically guided nucleic acid frameworks for regulating blood clotting are discussed.