Accounts of Chemical Research最新文献

The 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.

Near-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.

Liquid 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 à la carte.

Continuous 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.

Asymmetric 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 in situ 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.