Pub Date : 2026-04-03DOI: 10.1021/acs.accounts.5c00763
Ritika Sharma, Florence Mus, Lauren M Pellows, Peter J Dahl, David W Mulder, Zhi-Yong Yang, Paul W King, Gordana Dukovic, Lance C Seefeldt, John W Peters
<p><p>ConspectusDeveloping systems that can efficiently capture photon energy and convert this energy into fuels and chemicals requires understanding how to assemble molecular components with diverse functions into complete systems possessing selectivity and efficiency in directing charge carriers to catalytic reactions. There are many challenges to achieving this goal. One promising approach is the development of hybrid systems that combine semiconductor nanocrystals (NCs) for light capture and enzymes as efficient catalysts.Such biohybrid systems capitalize on the tunable electronic and optical properties of NCs while leveraging the unmatched specificity and efficiency of enzymes in catalyzing chemical reactions, thereby offering opportunities to surpass the limitations of each component alone. Here, we focus on recent progress in developing a biohybrid system that combines CdS NCs for photon capture with the enzyme nitrogenase to accomplish light-driven dinitrogen (N<sub>2</sub>) reduction to ammonia (NH<sub>3</sub>). Integrating light-harvesting materials with biological catalysts requires a deep understanding of NC properties, protein stability, and electron transfer (ET), making it an inherently multidisciplinary problem.The reduction of N<sub>2</sub> to NH<sub>3</sub> is a challenging reaction, with a high demand in both agriculture and industrial chemical production. This reaction is intrinsically energy intensive, due to the need to activate the N≡N triple bond. The current standard industrial approach to N<sub>2</sub> reduction, the Haber-Bosch reaction, obtains the necessary energy input from fossil fuels, whereas biological systems capable of N<sub>2</sub> reduction utilize the hydrolysis of ATP as their energy source. Replacing these costly, energy-intensive inputs with renewable light energy represents a critical step toward sustainable NH<sub>3</sub> production.Recent progress has demonstrated that semiconductor CdS NCs can be coupled to the catalytic component of nitrogenase, the MoFe protein, to form a biohybrid CdS NC:MoFe protein complex, enabling light-driven N<sub>2</sub> reduction rather than energy input from fossil fuels or ATP. This illustrates how inorganic NCs can functionally replace the natural Fe protein partner, yielding a biohybrid catalyst that enables controlled electron delivery and provides not only light-driven NH<sub>3</sub> production but also new approaches for probing enzyme catalytic function.The CdS NC:MoFe protein biohybrid system enables light-initiated electron delivery at ambient temperature, as well as temperatures below freezing, allowing for stabilization and spectroscopic characterization of key reaction intermediates. These findings highlight how photochemical biohybrids can serve as both functional catalysts and mechanistic probes. Beyond studies of the nitrogenase mechanism, studies of the CdS NC:MoFe system reveal how variables such as NC size, electrostatic binding interactions, and sacrific
{"title":"Mechanistic Insights into Dinitrogen Reduction to Ammonia in Light-Controlled Nanocrystal:Nitrogenase Complexes.","authors":"Ritika Sharma, Florence Mus, Lauren M Pellows, Peter J Dahl, David W Mulder, Zhi-Yong Yang, Paul W King, Gordana Dukovic, Lance C Seefeldt, John W Peters","doi":"10.1021/acs.accounts.5c00763","DOIUrl":"10.1021/acs.accounts.5c00763","url":null,"abstract":"<p><p>ConspectusDeveloping systems that can efficiently capture photon energy and convert this energy into fuels and chemicals requires understanding how to assemble molecular components with diverse functions into complete systems possessing selectivity and efficiency in directing charge carriers to catalytic reactions. There are many challenges to achieving this goal. One promising approach is the development of hybrid systems that combine semiconductor nanocrystals (NCs) for light capture and enzymes as efficient catalysts.Such biohybrid systems capitalize on the tunable electronic and optical properties of NCs while leveraging the unmatched specificity and efficiency of enzymes in catalyzing chemical reactions, thereby offering opportunities to surpass the limitations of each component alone. Here, we focus on recent progress in developing a biohybrid system that combines CdS NCs for photon capture with the enzyme nitrogenase to accomplish light-driven dinitrogen (N<sub>2</sub>) reduction to ammonia (NH<sub>3</sub>). Integrating light-harvesting materials with biological catalysts requires a deep understanding of NC properties, protein stability, and electron transfer (ET), making it an inherently multidisciplinary problem.The reduction of N<sub>2</sub> to NH<sub>3</sub> is a challenging reaction, with a high demand in both agriculture and industrial chemical production. This reaction is intrinsically energy intensive, due to the need to activate the N≡N triple bond. The current standard industrial approach to N<sub>2</sub> reduction, the Haber-Bosch reaction, obtains the necessary energy input from fossil fuels, whereas biological systems capable of N<sub>2</sub> reduction utilize the hydrolysis of ATP as their energy source. Replacing these costly, energy-intensive inputs with renewable light energy represents a critical step toward sustainable NH<sub>3</sub> production.Recent progress has demonstrated that semiconductor CdS NCs can be coupled to the catalytic component of nitrogenase, the MoFe protein, to form a biohybrid CdS NC:MoFe protein complex, enabling light-driven N<sub>2</sub> reduction rather than energy input from fossil fuels or ATP. This illustrates how inorganic NCs can functionally replace the natural Fe protein partner, yielding a biohybrid catalyst that enables controlled electron delivery and provides not only light-driven NH<sub>3</sub> production but also new approaches for probing enzyme catalytic function.The CdS NC:MoFe protein biohybrid system enables light-initiated electron delivery at ambient temperature, as well as temperatures below freezing, allowing for stabilization and spectroscopic characterization of key reaction intermediates. These findings highlight how photochemical biohybrids can serve as both functional catalysts and mechanistic probes. Beyond studies of the nitrogenase mechanism, studies of the CdS NC:MoFe system reveal how variables such as NC size, electrostatic binding interactions, and sacrific","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":""},"PeriodicalIF":17.7,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-02-23DOI: 10.1021/acs.accounts.5c00854
Benjamin Eller, , , Zhulfaa Zhulficar, , , Fatemeh Hajikarimi, , and , YuHuang Wang*,
<p >Ultrashort single-walled carbon nanotubes (SWCNTs), defined here as ∼1 to 50 nm segments, match the characteristic dimensions of biological pores, nanofluidic channels, and emerging quantum architectures, where quantum confinement, topological edge states─electronic states localized at the tube termini─and atomic defects converge to generate new functionalities for sensing, imaging, and optoelectronics. Yet this length regime has been largely inaccessible optically: ultrashort SWCNTs rarely emit light because mobile excitons rapidly diffuse to quenching sites at the tube ends. Fluorescent ultrashort nanotubes (FUNs) overcome this “dark gap” by introducing sp<sup>3</sup> quantum defects, also known as organic color centers (OCCs), that localize excitons and render them radiative, enabling bright photoluminescence in the short-wave infrared, including the NIR-II bioimaging window.</p><p >The FUN platform arises from three complementary advances: (1) quantum defect chemistry, which introduces molecularly tunable exciton traps; (2) super-resolution fluorescence imaging, which resolves discrete, end-localized emission sites in <40 nm nanotubes, demonstrating defect-governed radiative recombination; and (3) defect-induced chemical etching (DICE), which cuts nanotubes at preinstalled quantum defects to yield ultrashort, bright-emitting nanotube segments with intact graphitic frameworks and chemically defined termini. DICE further extends this chemical programmability by producing ultrashort nanotubes whose rim chemistry functions as molecular gates that reversibly regulate ionic transport through subnanometer pores. Beyond enabling bright ultrashort emitters and molecular gates, FUNs reveal a fundamental separation between host and defect excitons. The host SWCNT bright exciton transition (<i>E</i><sub>11</sub>) blue-shifts with decreasing length, following a Δ<i>E</i><sub>11</sub> ∝ <i>L</i><sup>–1/2</sup> scaling, whereas the defect state (<i>E</i><sub>sp3</sub>, historically denoted <i>E</i><sub>11</sub><sup>–</sup> or <i>E</i><sub>11</sub><sup>*</sup>) remains nearly invariant with length, consistent with a deep, localized exciton trap. This length–energy decoupling provides two independent design parameters (i.e., nanotube length and localized defect chemistry) for engineering exciton energetics at ultrashort length scales.</p><p >This Account traces the development of FUNs from their origins in quantum-defect chemistry to their emerging applications. We highlight how precise control over defect structure, nanotube length, and rim functionality converts previously dark ultrashort segments into a chemically precise architecture for codesigning quantum confinement, photophysics, and molecular function within a single carbon scaffold. We further discuss the opportunities and challenges ahead, pointing toward applications ranging from biomimetic channel mimics and responsive nanofluidic elements to infrared imaging probes and deterministic quant
{"title":"Fluorescent Ultrashort Nanotubes","authors":"Benjamin Eller, , , Zhulfaa Zhulficar, , , Fatemeh Hajikarimi, , and , YuHuang Wang*, ","doi":"10.1021/acs.accounts.5c00854","DOIUrl":"10.1021/acs.accounts.5c00854","url":null,"abstract":"<p >Ultrashort single-walled carbon nanotubes (SWCNTs), defined here as ∼1 to 50 nm segments, match the characteristic dimensions of biological pores, nanofluidic channels, and emerging quantum architectures, where quantum confinement, topological edge states─electronic states localized at the tube termini─and atomic defects converge to generate new functionalities for sensing, imaging, and optoelectronics. Yet this length regime has been largely inaccessible optically: ultrashort SWCNTs rarely emit light because mobile excitons rapidly diffuse to quenching sites at the tube ends. Fluorescent ultrashort nanotubes (FUNs) overcome this “dark gap” by introducing sp<sup>3</sup> quantum defects, also known as organic color centers (OCCs), that localize excitons and render them radiative, enabling bright photoluminescence in the short-wave infrared, including the NIR-II bioimaging window.</p><p >The FUN platform arises from three complementary advances: (1) quantum defect chemistry, which introduces molecularly tunable exciton traps; (2) super-resolution fluorescence imaging, which resolves discrete, end-localized emission sites in <40 nm nanotubes, demonstrating defect-governed radiative recombination; and (3) defect-induced chemical etching (DICE), which cuts nanotubes at preinstalled quantum defects to yield ultrashort, bright-emitting nanotube segments with intact graphitic frameworks and chemically defined termini. DICE further extends this chemical programmability by producing ultrashort nanotubes whose rim chemistry functions as molecular gates that reversibly regulate ionic transport through subnanometer pores. Beyond enabling bright ultrashort emitters and molecular gates, FUNs reveal a fundamental separation between host and defect excitons. The host SWCNT bright exciton transition (<i>E</i><sub>11</sub>) blue-shifts with decreasing length, following a Δ<i>E</i><sub>11</sub> ∝ <i>L</i><sup>–1/2</sup> scaling, whereas the defect state (<i>E</i><sub>sp3</sub>, historically denoted <i>E</i><sub>11</sub><sup>–</sup> or <i>E</i><sub>11</sub><sup>*</sup>) remains nearly invariant with length, consistent with a deep, localized exciton trap. This length–energy decoupling provides two independent design parameters (i.e., nanotube length and localized defect chemistry) for engineering exciton energetics at ultrashort length scales.</p><p >This Account traces the development of FUNs from their origins in quantum-defect chemistry to their emerging applications. We highlight how precise control over defect structure, nanotube length, and rim functionality converts previously dark ultrashort segments into a chemically precise architecture for codesigning quantum confinement, photophysics, and molecular function within a single carbon scaffold. We further discuss the opportunities and challenges ahead, pointing toward applications ranging from biomimetic channel mimics and responsive nanofluidic elements to infrared imaging probes and deterministic quant","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"861–874"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146778749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-02-25DOI: 10.1021/acs.accounts.5c00916
Yuxia Liu, , , Jiaye Chen, , and , Xiaogang Liu*,
<p >Photon upconversion, which converts low-energy near-infrared light into higher-energy emission, has emerged as a powerful tool at the intersection of photophysics, materials science, and biosensing. The nonlinear excitation, large anti-Stokes shifts, minimal background autofluorescence, high photostability, and effective tissue penetration of photon upconversion make it particularly attractive for probing biological systems under physiologically relevant conditions.</p><p >Lanthanide-doped nanoparticles constitute a dominant class of upconversion systems. Encapsulation of lanthanide ions within crystalline hosts shields their 4f electronic states from environmental perturbations, enabling spectrally stable and temporally persistent emission. Nevertheless, their relatively low quantum yields under biologically safe irradiation often necessitate higher excitation power densities, which limit their <i>in vivo</i> applications. To address this challenge, advances in materials design, most notably core–shell architectures that regulate energy migration and suppress surface quenching, have substantially boosted upconversion efficiency and spectral tunability. Complementary surface engineering via chemical modifications has further enhanced colloid stability, biocompatibility, and targeting specificity. In parallel, optical field engineering strategies, including superlensing effects and plasmonic coupling, have expanded the functional scope of upconversion platforms beyond conventional luminescence. Together, these developments have established upconversion nanoparticles as a robust physical interface between optical excitation and biological response.</p><p >In this Account, we focus on recent progress in integrating upconversion nanoparticles with diverse physical modalities for biosensing and biointerfacing. We first outline the photophysical principles underlying photon upconversion and summarize key strategies for enhancing efficiency and signal fidelity. We then survey upconversion nanoparticle-based platforms that couple optical emission with electrical, mechanical, and thermal readouts. In optical microscopy, upconversion nanoparticles enable long-term single-particle tracking of neuronal transport and support super-resolution imaging through nonlinear emission processes and surface-migration depletion. When interfaced with electrophysiological measurements, these nanoparticles allow real-time monitoring of transmembrane water transport including flux through ion channels. Upconversion-assisted optogenetics further enables noninvasive neuromodulation without implanting optical fibers. Besides optical and electrical modalities, upconversion nanoparticles have been applied to force sensing over a wide dynamic range and to subcellular thermometry with high spatial precision. Incorporation of upconversion nanoparticles into device architectures extends these capabilities to stochastic photoluminescence encoding, infrared vision through retinal
{"title":"Photophysics-Guided Upconversion Nanosystems for Sensing","authors":"Yuxia Liu, , , Jiaye Chen, , and , Xiaogang Liu*, ","doi":"10.1021/acs.accounts.5c00916","DOIUrl":"10.1021/acs.accounts.5c00916","url":null,"abstract":"<p >Photon upconversion, which converts low-energy near-infrared light into higher-energy emission, has emerged as a powerful tool at the intersection of photophysics, materials science, and biosensing. The nonlinear excitation, large anti-Stokes shifts, minimal background autofluorescence, high photostability, and effective tissue penetration of photon upconversion make it particularly attractive for probing biological systems under physiologically relevant conditions.</p><p >Lanthanide-doped nanoparticles constitute a dominant class of upconversion systems. Encapsulation of lanthanide ions within crystalline hosts shields their 4f electronic states from environmental perturbations, enabling spectrally stable and temporally persistent emission. Nevertheless, their relatively low quantum yields under biologically safe irradiation often necessitate higher excitation power densities, which limit their <i>in vivo</i> applications. To address this challenge, advances in materials design, most notably core–shell architectures that regulate energy migration and suppress surface quenching, have substantially boosted upconversion efficiency and spectral tunability. Complementary surface engineering via chemical modifications has further enhanced colloid stability, biocompatibility, and targeting specificity. In parallel, optical field engineering strategies, including superlensing effects and plasmonic coupling, have expanded the functional scope of upconversion platforms beyond conventional luminescence. Together, these developments have established upconversion nanoparticles as a robust physical interface between optical excitation and biological response.</p><p >In this Account, we focus on recent progress in integrating upconversion nanoparticles with diverse physical modalities for biosensing and biointerfacing. We first outline the photophysical principles underlying photon upconversion and summarize key strategies for enhancing efficiency and signal fidelity. We then survey upconversion nanoparticle-based platforms that couple optical emission with electrical, mechanical, and thermal readouts. In optical microscopy, upconversion nanoparticles enable long-term single-particle tracking of neuronal transport and support super-resolution imaging through nonlinear emission processes and surface-migration depletion. When interfaced with electrophysiological measurements, these nanoparticles allow real-time monitoring of transmembrane water transport including flux through ion channels. Upconversion-assisted optogenetics further enables noninvasive neuromodulation without implanting optical fibers. Besides optical and electrical modalities, upconversion nanoparticles have been applied to force sensing over a wide dynamic range and to subcellular thermometry with high spatial precision. Incorporation of upconversion nanoparticles into device architectures extends these capabilities to stochastic photoluminescence encoding, infrared vision through retinal ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"1043–1055"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147279969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-02-23DOI: 10.1021/acs.accounts.5c00858
Siming Chen, , , Shiyi Chen, , , Ye Tao*, , , Runfeng Chen*, , and , Wei Huang*,
<p >Smart materials capable of in situ self-responding to external stimuli are proliferating due to their promising properties for advanced applications, including liquid crystal displays, information encryption, visual sensing, and substance detections. Significant progress has been made in designing and developing novel smart materials ranging from memory polymers to phase-change materials, color-change materials, etc. Inspired by these advances, the integration of intelligent functional groups into organic semiconductors offers a promising path to endow optoelectronic materials with selectively adaptive and dynamic features. This integration enables real-time, controllable, and repeatable responses to environmental changes, which allows optoelectronic materials to dynamically adjust their properties during processes such as carrier transport, energy transfer, and radiative/nonradiative exciton decay in device operation for achieving enhanced device performance. However, the development of intelligent structures remains challenging, and the lack of rational strategies for effectively integrating these structures with functional building blocks continues to impede the progress of smart optoelectronic materials.</p><p >In this Account, a concise, universal, and effective tactic, called resonance variation-based dynamic adaptation (RVDA), to design and construct smart organic optoelectronic materials by incorporating resonance structures into organic building blocks has been proposed. RVDA materials through facile interconversion between canonical forms enable significant enhancement of optoelectronic properties through dynamic modulation of electronic characteristics including charge distribution, energy levels, spin–orbit coupling (SOC), and charge transport properties. Nevertheless, in-depth and comprehensive reviews on the progress of RVDA are still lacking. Therefore, this Account aims to summarize our research on the molecular design and properties of RVDA materials, along with recent advances across diverse application fields. It begins by introducing the fundamental principles of RVDA in dynamically modulating optoelectronic properties, following by the four systems based on their molecular structure design considerations. We highlight the diverse types of RVDA materials while discussing recent developments, including the latest research on host materials for organic light-emitting diodes (OLEDs), organic ultralong room-temperature phosphorescence (OURTP) materials for data encryption, fluorescence emitters for sensors, and hole transport materials (HTMs) for perovskite solar cells (PSCs). A key objective of this Account is to extract the fundamental design principles of RVDA materials and to uncover the common relationships between molecular structures and their optoelectronic properties across different research areas, systematizing our understanding of this field. Finally, current challenges are analyzed to outline future research direc
{"title":"Resonance Variation-Based Dynamically Adaptive Organic Optoelectronic Materials","authors":"Siming Chen, , , Shiyi Chen, , , Ye Tao*, , , Runfeng Chen*, , and , Wei Huang*, ","doi":"10.1021/acs.accounts.5c00858","DOIUrl":"10.1021/acs.accounts.5c00858","url":null,"abstract":"<p >Smart materials capable of in situ self-responding to external stimuli are proliferating due to their promising properties for advanced applications, including liquid crystal displays, information encryption, visual sensing, and substance detections. Significant progress has been made in designing and developing novel smart materials ranging from memory polymers to phase-change materials, color-change materials, etc. Inspired by these advances, the integration of intelligent functional groups into organic semiconductors offers a promising path to endow optoelectronic materials with selectively adaptive and dynamic features. This integration enables real-time, controllable, and repeatable responses to environmental changes, which allows optoelectronic materials to dynamically adjust their properties during processes such as carrier transport, energy transfer, and radiative/nonradiative exciton decay in device operation for achieving enhanced device performance. However, the development of intelligent structures remains challenging, and the lack of rational strategies for effectively integrating these structures with functional building blocks continues to impede the progress of smart optoelectronic materials.</p><p >In this Account, a concise, universal, and effective tactic, called resonance variation-based dynamic adaptation (RVDA), to design and construct smart organic optoelectronic materials by incorporating resonance structures into organic building blocks has been proposed. RVDA materials through facile interconversion between canonical forms enable significant enhancement of optoelectronic properties through dynamic modulation of electronic characteristics including charge distribution, energy levels, spin–orbit coupling (SOC), and charge transport properties. Nevertheless, in-depth and comprehensive reviews on the progress of RVDA are still lacking. Therefore, this Account aims to summarize our research on the molecular design and properties of RVDA materials, along with recent advances across diverse application fields. It begins by introducing the fundamental principles of RVDA in dynamically modulating optoelectronic properties, following by the four systems based on their molecular structure design considerations. We highlight the diverse types of RVDA materials while discussing recent developments, including the latest research on host materials for organic light-emitting diodes (OLEDs), organic ultralong room-temperature phosphorescence (OURTP) materials for data encryption, fluorescence emitters for sensors, and hole transport materials (HTMs) for perovskite solar cells (PSCs). A key objective of this Account is to extract the fundamental design principles of RVDA materials and to uncover the common relationships between molecular structures and their optoelectronic properties across different research areas, systematizing our understanding of this field. Finally, current challenges are analyzed to outline future research direc","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"875–888"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-02-27DOI: 10.1021/acs.accounts.6c00010
Kun Yin, , , Shichao Lin*, , and , Chaoyong Yang*,
<p >Gene expression of cells is a highly heterogeneous and dynamic program that changes over time in various biological processes such as embryogenesis, disease progression, and response to stimuli. Understanding the molecular mechanisms of heterogeneous and dynamic gene expression is crucial for advancing our knowledge of health and disease. The recent development of single-cell RNA sequencing (scRNA-seq) technologies has offered a great opportunity to dissect cellular heterogeneity by profiling the transcriptomes of individual cells. However, scRNA-seq captures only static snapshots of gene expression and fails to temporally resolve the RNA dynamics. Therefore, the rapid changes in transcription, the coordinated regulation of RNA synthesis and degradation rates, and the cellular interactions driving cell fate decisions remain poorly understood. In the past few years, metabolic RNA labeling-based scRNA-seq has emerged as a cutting-edge chemical tool to tackle these challenges. Nucleoside analogs are applied to label newly transcribed RNAs and distinguish them from pre-existing RNAs. This time-resolved technology unbiasedly captures the true RNA dynamics for thousands of genes in each of the individual cells, providing unprecedented insight into the regulation of heterogeneous and dynamic gene expression in diverse biological processes.</p><p >In this Account, we highlight the recent advances achieved by our group and other laboratories in metabolic RNA labeling-enabled time-resolved scRNA-seq. First, we summarize the recent development of time-resolved scRNA-seq by integrating metabolic RNA labeling (e.g., 4-thioridine labeling) with various scRNA-seq platforms. We highlight our size-exclusion and locally quasi-static hydrodynamics-based Well-TEMP-seq method, which greatly improves the performance of time-resolved scRNA-seq (higher throughput, higher cell barcoding efficiency, and RNA recovery rate) and lowers the cost. Next, we extend the labeling strategy from single nucleoside labeling to double nucleoside labeling and develop scDUAL-seq The sequential (pulse–pulse) labeling by two different nucleosides in scDUAL-seq addresses the limitation of single nucleoside labeling in the simultaneous monitoring of RNA synthesis and degradation processes and accurate measurement of RNA kinetics. The ability of scDUAL-seq to discriminate between different cell states also allows the unveiling of the interplay between RNA synthesis and degradation that controls distinct RNA regulatory strategy transitions during dynamic processes. Then, we discuss the further development of in vivo metabolic RNA labeling-based scRNA-seq by our laboratory (Dyna-vivo-seq) and others, which advances the time-resolved scRNA-seq studies from cultured cells to animal models. This innovation opens new avenues to reveal single-cell RNA dynamics in living organisms. Finally, we introduce our attempts to integrate time-resolved scRNA-seq with spatial transcriptomics, adding a spati
{"title":"Metabolic RNA Labeling-Enabled Time-Resolved Single-Cell RNA Sequencing","authors":"Kun Yin, , , Shichao Lin*, , and , Chaoyong Yang*, ","doi":"10.1021/acs.accounts.6c00010","DOIUrl":"10.1021/acs.accounts.6c00010","url":null,"abstract":"<p >Gene expression of cells is a highly heterogeneous and dynamic program that changes over time in various biological processes such as embryogenesis, disease progression, and response to stimuli. Understanding the molecular mechanisms of heterogeneous and dynamic gene expression is crucial for advancing our knowledge of health and disease. The recent development of single-cell RNA sequencing (scRNA-seq) technologies has offered a great opportunity to dissect cellular heterogeneity by profiling the transcriptomes of individual cells. However, scRNA-seq captures only static snapshots of gene expression and fails to temporally resolve the RNA dynamics. Therefore, the rapid changes in transcription, the coordinated regulation of RNA synthesis and degradation rates, and the cellular interactions driving cell fate decisions remain poorly understood. In the past few years, metabolic RNA labeling-based scRNA-seq has emerged as a cutting-edge chemical tool to tackle these challenges. Nucleoside analogs are applied to label newly transcribed RNAs and distinguish them from pre-existing RNAs. This time-resolved technology unbiasedly captures the true RNA dynamics for thousands of genes in each of the individual cells, providing unprecedented insight into the regulation of heterogeneous and dynamic gene expression in diverse biological processes.</p><p >In this Account, we highlight the recent advances achieved by our group and other laboratories in metabolic RNA labeling-enabled time-resolved scRNA-seq. First, we summarize the recent development of time-resolved scRNA-seq by integrating metabolic RNA labeling (e.g., 4-thioridine labeling) with various scRNA-seq platforms. We highlight our size-exclusion and locally quasi-static hydrodynamics-based Well-TEMP-seq method, which greatly improves the performance of time-resolved scRNA-seq (higher throughput, higher cell barcoding efficiency, and RNA recovery rate) and lowers the cost. Next, we extend the labeling strategy from single nucleoside labeling to double nucleoside labeling and develop scDUAL-seq The sequential (pulse–pulse) labeling by two different nucleosides in scDUAL-seq addresses the limitation of single nucleoside labeling in the simultaneous monitoring of RNA synthesis and degradation processes and accurate measurement of RNA kinetics. The ability of scDUAL-seq to discriminate between different cell states also allows the unveiling of the interplay between RNA synthesis and degradation that controls distinct RNA regulatory strategy transitions during dynamic processes. Then, we discuss the further development of in vivo metabolic RNA labeling-based scRNA-seq by our laboratory (Dyna-vivo-seq) and others, which advances the time-resolved scRNA-seq studies from cultured cells to animal models. This innovation opens new avenues to reveal single-cell RNA dynamics in living organisms. Finally, we introduce our attempts to integrate time-resolved scRNA-seq with spatial transcriptomics, adding a spati","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"1056–1069"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147315736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-03-05DOI: 10.1021/acs.accounts.5c00842
Ronny Hardegger, and , Oliver S. Wenger*,
<p >One of the most central questions in chemistry is how a starting material can be converted as simply and efficiently as possible into a product. The answer may include photocatalysis, and if the reaction proceeds well, one might argue that understanding the underlying mechanism is not essential. Even if the reaction does not perform as anticipated, condition screening may still provide the operationally simplest and most effective path to the desired outcome, while mechanistic aspects can remain largely unexamined. Given the large parameter space typically associated with modern photocatalytic reactions, this approach is both plausible and justified, particularly when product synthesis is the primary goal.</p><p >A complementary perspective on modern photocatalysis focuses on the conceptual advancement of photochemistry and a deeper understanding of its elementary steps and their interplay. This type of research begins with classical mechanistic elucidation to break down complex processes into individual elementary events. Once sufficient understanding has been achieved, it can lead to the mechanistic design of photoreactions. At that stage, the sequence of photophysical and chemical events triggered by light, and consequently the overall outcome of the reaction, can become rationally predictable, at least in principle.</p><p >In this Account, we examine how the cross-fertilization between synthetically oriented photoredox catalysis, which is primarily concerned with the activation and functionalization of organic molecules, and mechanistically driven research from the physical–inorganic domain has advanced the field of photochemistry. This interaction has often been catalyzed by controversial discussions surrounding the mechanistic details of reactions that have attracted significant synthetic interest. As a result, this interplay has propelled significant advances across several critical areas of modern molecular photocatalysis, including the reactivity of excited-state organic radicals and solvated electrons, the mechanisms underlying multiphoton excitation processes such as photon upconversion, the puzzling light-independent energy-loss phenomenon known as “cage escape”, and even the possibility of challenging Kasha’s rule, a foundational principle in photophysics with profound implications for photochemistry.</p><p >The knowledge accumulated through this work has brought the field closer to achieving mechanistically guided design in photocatalysis, extending far beyond the initial light-induced step. Central to this advancement are modern time-resolved spectroscopic methods, which have provided crucial insights into transient species and reaction dynamics. This conceptual strategy opens new opportunities and highlights challenges in redefining thermodynamic and kinetic limits. Ultimately, combining mechanistic insight with the practical expertise of synthetic chemists offers great potential for continued innovation in photoredox catalysi
{"title":"Mechanistic Design in Photocatalysis","authors":"Ronny Hardegger, and , Oliver S. Wenger*, ","doi":"10.1021/acs.accounts.5c00842","DOIUrl":"10.1021/acs.accounts.5c00842","url":null,"abstract":"<p >One of the most central questions in chemistry is how a starting material can be converted as simply and efficiently as possible into a product. The answer may include photocatalysis, and if the reaction proceeds well, one might argue that understanding the underlying mechanism is not essential. Even if the reaction does not perform as anticipated, condition screening may still provide the operationally simplest and most effective path to the desired outcome, while mechanistic aspects can remain largely unexamined. Given the large parameter space typically associated with modern photocatalytic reactions, this approach is both plausible and justified, particularly when product synthesis is the primary goal.</p><p >A complementary perspective on modern photocatalysis focuses on the conceptual advancement of photochemistry and a deeper understanding of its elementary steps and their interplay. This type of research begins with classical mechanistic elucidation to break down complex processes into individual elementary events. Once sufficient understanding has been achieved, it can lead to the mechanistic design of photoreactions. At that stage, the sequence of photophysical and chemical events triggered by light, and consequently the overall outcome of the reaction, can become rationally predictable, at least in principle.</p><p >In this Account, we examine how the cross-fertilization between synthetically oriented photoredox catalysis, which is primarily concerned with the activation and functionalization of organic molecules, and mechanistically driven research from the physical–inorganic domain has advanced the field of photochemistry. This interaction has often been catalyzed by controversial discussions surrounding the mechanistic details of reactions that have attracted significant synthetic interest. As a result, this interplay has propelled significant advances across several critical areas of modern molecular photocatalysis, including the reactivity of excited-state organic radicals and solvated electrons, the mechanisms underlying multiphoton excitation processes such as photon upconversion, the puzzling light-independent energy-loss phenomenon known as “cage escape”, and even the possibility of challenging Kasha’s rule, a foundational principle in photophysics with profound implications for photochemistry.</p><p >The knowledge accumulated through this work has brought the field closer to achieving mechanistically guided design in photocatalysis, extending far beyond the initial light-induced step. Central to this advancement are modern time-resolved spectroscopic methods, which have provided crucial insights into transient species and reaction dynamics. This conceptual strategy opens new opportunities and highlights challenges in redefining thermodynamic and kinetic limits. Ultimately, combining mechanistic insight with the practical expertise of synthetic chemists offers great potential for continued innovation in photoredox catalysi","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"849–860"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13001088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147352944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p >The escalating global energy crisis, coupled with the environmental impact of conventional energy consumption, has intensified the pursuit of green and sustainable energy solutions. Converting low-grade heat into electricity using flexible, lightweight, and solution-processable polymeric thermoelectrics offers unique opportunities for next-generation wearable and portable power systems. Early studies in this field predominantly emphasized molecular design, optimizing conjugated backbones and side chains to enhance the charge transport and Seebeck coefficients. These efforts yielded valuable insights into the relationships among molecular structure, electronic states, and thermoelectric performance. More recently, molecular assembly engineering has attracted growing interest driven by recognition of how microstructural order and hierarchical morphology affect carrier mobility and energy filtering. Strategies such as controlled self-assembly, directional alignment, and interface engineering have proven highly effective, enabling property enhancement beyond the limits of molecular design alone. This shift has not only produced high-performance polymeric thermoelectric materials but also broadened their functional scope, opening opportunities for integration into flexible and versatile energy systems.</p><p >The “phonon-glass, electron-crystal” (PGEC) concept envisions an ideal assembly that combines the intrinsically low thermal conductivity of amorphous glasses with the exceptional charge transport of crystalline solids. Guided by these design principles, our recent work has addressed the coupled optimization of charge and thermal transport while exploring novel functional capabilities in polymeric thermoelectrics. To mitigate the persistent trade-off between the Seebeck coefficient (<i>S</i>) and electrical conductivity (σ), we developed a mixed-orientation strategy in which bimodal molecular orientation generates interfacial weak hydrogen bonds, promoting efficient chemical doping, improved molecular ordering, and increased density of states. This synergistic effect yielded simultaneous enhancements in <i>S</i> and σ, achieving a peak figure of merit (<i>ZT</i>) more than four times higher than that of single-orientation films. In addition, we tackled the underestimated role of thermal conductivity (κ) by introducing a heterogeneous assembly approach for high-mobility polymers. Incorporating porous architectures induced localized vibrational scattering, lowering lattice κ and raising <i>ZT</i> to 0.52. Building further, we introduced a polymeric multi-heterojunction (PMHJ) architecture via cross-linking-assisted assembly, where pronounced size effects and interfacial diffuse scattering reduced κ to 0.10 W·m<sup>–1</sup>·K<sup>–1</sup>, delivering a record-high <i>ZT</i> of 1.28, comparable to that of commercial Bi<sub>2</sub>Te<sub>3</sub> materials in the near-room-temperature region. Extending beyond performance metrics, we revealed anomalo
{"title":"Engineering Molecular Assembly for High Performance Plastic Thermoelectrics","authors":"Dongyang Wang, , , Daoben Zhu, , and , Chong-an Di*, ","doi":"10.1021/acs.accounts.5c00867","DOIUrl":"10.1021/acs.accounts.5c00867","url":null,"abstract":"<p >The escalating global energy crisis, coupled with the environmental impact of conventional energy consumption, has intensified the pursuit of green and sustainable energy solutions. Converting low-grade heat into electricity using flexible, lightweight, and solution-processable polymeric thermoelectrics offers unique opportunities for next-generation wearable and portable power systems. Early studies in this field predominantly emphasized molecular design, optimizing conjugated backbones and side chains to enhance the charge transport and Seebeck coefficients. These efforts yielded valuable insights into the relationships among molecular structure, electronic states, and thermoelectric performance. More recently, molecular assembly engineering has attracted growing interest driven by recognition of how microstructural order and hierarchical morphology affect carrier mobility and energy filtering. Strategies such as controlled self-assembly, directional alignment, and interface engineering have proven highly effective, enabling property enhancement beyond the limits of molecular design alone. This shift has not only produced high-performance polymeric thermoelectric materials but also broadened their functional scope, opening opportunities for integration into flexible and versatile energy systems.</p><p >The “phonon-glass, electron-crystal” (PGEC) concept envisions an ideal assembly that combines the intrinsically low thermal conductivity of amorphous glasses with the exceptional charge transport of crystalline solids. Guided by these design principles, our recent work has addressed the coupled optimization of charge and thermal transport while exploring novel functional capabilities in polymeric thermoelectrics. To mitigate the persistent trade-off between the Seebeck coefficient (<i>S</i>) and electrical conductivity (σ), we developed a mixed-orientation strategy in which bimodal molecular orientation generates interfacial weak hydrogen bonds, promoting efficient chemical doping, improved molecular ordering, and increased density of states. This synergistic effect yielded simultaneous enhancements in <i>S</i> and σ, achieving a peak figure of merit (<i>ZT</i>) more than four times higher than that of single-orientation films. In addition, we tackled the underestimated role of thermal conductivity (κ) by introducing a heterogeneous assembly approach for high-mobility polymers. Incorporating porous architectures induced localized vibrational scattering, lowering lattice κ and raising <i>ZT</i> to 0.52. Building further, we introduced a polymeric multi-heterojunction (PMHJ) architecture via cross-linking-assisted assembly, where pronounced size effects and interfacial diffuse scattering reduced κ to 0.10 W·m<sup>–1</sup>·K<sup>–1</sup>, delivering a record-high <i>ZT</i> of 1.28, comparable to that of commercial Bi<sub>2</sub>Te<sub>3</sub> materials in the near-room-temperature region. Extending beyond performance metrics, we revealed anomalo","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"932–944"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147359034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p >Alzheimer’s disease (AD) is a common neurodegenerative disease, one of whose pathological characteristics is the abnormal deposition of amyloid beta (Aβ). The development of highly sensitive and specific Aβ imaging probes is of great significance for diagnosis, therapeutic discovery, and pathological mechanism studies of AD. In recent years, small molecule-based optical probes have shown significant potential for in vivo whole-brain imaging in small animals and high-resolution microscopic imaging of biological processes, advancing Aβ imaging from detection to molecular mechanisms study and drug discovery. Therefore, the rational design and efficient application of these small molecular probes in Aβ imaging and therapy remain active areas of research. In this regard, a comprehensive understanding of the design strategy of the Aβ probes is highly desirable for advancing and guiding future research directions.</p><p >Over the past decade, our research has been focused on a trilogy of developing Aβ-based small molecules as imaging probes and therapeutics. In episode I, we invented a brand-new family of near-infrared fluorescent (NIRF) probes CRANAD-Xs, for in vivo selective imaging of Aβ species in AD mice. Considering that different Aβ species exhibit distinct neurotoxicities─with soluble oligomers regarded as the most toxic and insoluble plaques representing a less toxic, late stage of amyloidosis, we rationally designed the CRANAD-X series to cover the full spectrum of amyloid pathology, from low-toxicity plaques to highly toxic oligomers. Importantly, unlike most studies in this field that focus solely on probe characterization, we demonstrated that CRANAD-Xs can longitudinally monitor therapeutic efficacy in real time, supporting their use in drug discovery.</p><p >Although in vivo NIRF imaging with CRANAD-Xs shows great promise, it remains severely limited by shallow tissue penetration, largely due to autofluorescence interference and a low signal-to-noise ratio (SNR). Consequently, achieving sufficient imaging depth in vivo continues to be a major challenge. In episode II, we pioneered the exploration of chemiluminescence probes (ADLumin-Xs) for detecting Aβ species to meet the needs of deep imaging. Due to high SNR and deep imaging with ADLumin-Xs, we demonstrate the first in vivo 3D whole-brain imaging using chemiluminescence probes, enabling precise localization of Aβ deposits. In addition, using chemiluminescence resonance energy transfer (CRET) with dual nonconjugated probes, we achieve dual-amplification of the Aβ signal in vivo whole-brain imaging.</p><p >In episode III, we focus on molecularly produced light (“molecular light”) for AD therapeutics. Molecular light, primarily including chemiluminescence and bioluminescence, owns a dual nature as both a deliverable molecule and intrinsic light source that enables limitless tissue penetration unattainable with naturally/physically produced light. This dual nature supports theranostic
{"title":"Molecular Probes: From Aβ Imaging to Phototherapy in Alzheimer’s Disease","authors":"Zhiyong Jiang, , , Huizhe Wang, , , Jiang Yu, , , Shiju Gu, , , Jinwu Yan, , and , Chongzhao Ran*, ","doi":"10.1021/acs.accounts.5c00860","DOIUrl":"10.1021/acs.accounts.5c00860","url":null,"abstract":"<p >Alzheimer’s disease (AD) is a common neurodegenerative disease, one of whose pathological characteristics is the abnormal deposition of amyloid beta (Aβ). The development of highly sensitive and specific Aβ imaging probes is of great significance for diagnosis, therapeutic discovery, and pathological mechanism studies of AD. In recent years, small molecule-based optical probes have shown significant potential for in vivo whole-brain imaging in small animals and high-resolution microscopic imaging of biological processes, advancing Aβ imaging from detection to molecular mechanisms study and drug discovery. Therefore, the rational design and efficient application of these small molecular probes in Aβ imaging and therapy remain active areas of research. In this regard, a comprehensive understanding of the design strategy of the Aβ probes is highly desirable for advancing and guiding future research directions.</p><p >Over the past decade, our research has been focused on a trilogy of developing Aβ-based small molecules as imaging probes and therapeutics. In episode I, we invented a brand-new family of near-infrared fluorescent (NIRF) probes CRANAD-Xs, for in vivo selective imaging of Aβ species in AD mice. Considering that different Aβ species exhibit distinct neurotoxicities─with soluble oligomers regarded as the most toxic and insoluble plaques representing a less toxic, late stage of amyloidosis, we rationally designed the CRANAD-X series to cover the full spectrum of amyloid pathology, from low-toxicity plaques to highly toxic oligomers. Importantly, unlike most studies in this field that focus solely on probe characterization, we demonstrated that CRANAD-Xs can longitudinally monitor therapeutic efficacy in real time, supporting their use in drug discovery.</p><p >Although in vivo NIRF imaging with CRANAD-Xs shows great promise, it remains severely limited by shallow tissue penetration, largely due to autofluorescence interference and a low signal-to-noise ratio (SNR). Consequently, achieving sufficient imaging depth in vivo continues to be a major challenge. In episode II, we pioneered the exploration of chemiluminescence probes (ADLumin-Xs) for detecting Aβ species to meet the needs of deep imaging. Due to high SNR and deep imaging with ADLumin-Xs, we demonstrate the first in vivo 3D whole-brain imaging using chemiluminescence probes, enabling precise localization of Aβ deposits. In addition, using chemiluminescence resonance energy transfer (CRET) with dual nonconjugated probes, we achieve dual-amplification of the Aβ signal in vivo whole-brain imaging.</p><p >In episode III, we focus on molecularly produced light (“molecular light”) for AD therapeutics. Molecular light, primarily including chemiluminescence and bioluminescence, owns a dual nature as both a deliverable molecule and intrinsic light source that enables limitless tissue penetration unattainable with naturally/physically produced light. This dual nature supports theranostic ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"889–901"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146199562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metal catalysis has profoundly shaped the landscape of organic synthesis, driving advancements in chemical manufacturing, pharmaceuticals, and material science. While traditional mechanistic understanding has been largely based on mononuclear organometallic complexes and their elementary reaction steps, recent studies increasingly reveal that single metal species often undergo structural evolution to generate organometallic clusters, nanoclusters, and larger aggregates during catalytic processes. These in situ formed polynuclear organometallic clusters with diverse nuclearities, charges, and configurations not only impact catalytic efficiency and selectivity but also reshape the viewpoint about active species in metal catalysis. A deep understanding of this structural evolution process is highly needed to optimize catalytic performance, minimize catalyst loading, and lower metal residues in final products. Moreover, systematic studies on the synthesis, structural evaluation, and application of these polynuclear organometallic clusters will expand frontiers of cluster chemistry into many interdisciplinary fields. Over the past decade, we have successfully developed a cyclization-based synthetic strategy to achieve a series of structurally diverse polynuclear organometallic compounds and clusters (OMCs) of Group 11 metals. A key focus has been paid to the unique carbon-polymetallic bonding in OMCs, including the carbon–polymetal interactions of varying nuclearities and the newly discovered hyperconjugative aromaticity formed in gem-diaurated aryl complexes. Furthermore, we have unraveled two major pathways, redox-driven aggregation and ligand abstraction-caused assembly, to propel structural evolution from low nuclear number compounds to polymetallic organometallic nanoclusters containing several carbanionic units. The role of these in situ formed OMCs in catalytic reactions has been comprehensively evaluated and classified as active and inactive ingredients. Based on the understanding of the structures and reactivity of OMCs, we have exploited the applications of OMCs spanning catalysis, luminescent materials, and bioinorganic chemistry, particularly including the cancer therapy of hypercoordinated gold clusters via synergistic C–Au bond cleavage. Overall, in this Account we try to highlight designed synthesis of polynuclear organometallic compounds and clusters via a cyclization-based synthetic strategy, mechanistic studies on the reactivity of carbon–polymetal bonding therein and the structural evolution process from low to high nuclearity cluster transformation, and functional applications enabled by their distinctive bonding motifs. We hope that this summary can provide a novel perspective to bridge organic synthesis and cluster chemistry and open new avenues for designing functional polynuclear organometallic compounds and clusters.
{"title":"Organometallic Clusters in Catalysis: From Designed Synthesis and Structural Evolution to Functional Applications","authors":"Bo-Wei Zhou, , , Yangming Liu, , and , Liang Zhao*, ","doi":"10.1021/acs.accounts.5c00897","DOIUrl":"10.1021/acs.accounts.5c00897","url":null,"abstract":"<p >Metal catalysis has profoundly shaped the landscape of organic synthesis, driving advancements in chemical manufacturing, pharmaceuticals, and material science. While traditional mechanistic understanding has been largely based on mononuclear organometallic complexes and their elementary reaction steps, recent studies increasingly reveal that single metal species often undergo structural evolution to generate organometallic clusters, nanoclusters, and larger aggregates during catalytic processes. These <i>in situ</i> formed polynuclear organometallic clusters with diverse nuclearities, charges, and configurations not only impact catalytic efficiency and selectivity but also reshape the viewpoint about active species in metal catalysis. A deep understanding of this structural evolution process is highly needed to optimize catalytic performance, minimize catalyst loading, and lower metal residues in final products. Moreover, systematic studies on the synthesis, structural evaluation, and application of these polynuclear organometallic clusters will expand frontiers of cluster chemistry into many interdisciplinary fields. Over the past decade, we have successfully developed a cyclization-based synthetic strategy to achieve a series of structurally diverse polynuclear organometallic compounds and clusters (OMCs) of Group 11 metals. A key focus has been paid to the unique carbon-polymetallic bonding in OMCs, including the carbon–polymetal interactions of varying nuclearities and the newly discovered hyperconjugative aromaticity formed in <i>gem</i>-diaurated aryl complexes. Furthermore, we have unraveled two major pathways, redox-driven aggregation and ligand abstraction-caused assembly, to propel structural evolution from low nuclear number compounds to polymetallic organometallic nanoclusters containing several carbanionic units. The role of these <i>in situ</i> formed OMCs in catalytic reactions has been comprehensively evaluated and classified as active and inactive ingredients. Based on the understanding of the structures and reactivity of OMCs, we have exploited the applications of OMCs spanning catalysis, luminescent materials, and bioinorganic chemistry, particularly including the cancer therapy of hypercoordinated gold clusters via synergistic C–Au bond cleavage. Overall, in this Account we try to highlight designed synthesis of polynuclear organometallic compounds and clusters via a cyclization-based synthetic strategy, mechanistic studies on the reactivity of carbon–polymetal bonding therein and the structural evolution process from low to high nuclearity cluster transformation, and functional applications enabled by their distinctive bonding motifs. We hope that this summary can provide a novel perspective to bridge organic synthesis and cluster chemistry and open new avenues for designing functional polynuclear organometallic compounds and clusters.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"945–957"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147280021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17Epub Date: 2026-02-23DOI: 10.1021/acs.accounts.5c00900
Julia R. Shuluk, , , Hazel A. Fargher, , and , Eric V. Anslyn*,
<p >Polymer chemistry has expanded considerably over the past century to include studies of sequence-controlled and sequence-defined polymers. What began as a discipline focused largely on bulk polymer properties, such as mechanical strength, thermal behavior, and processability, has increasingly shifted toward molecular-level precision. These developments were inspired and enabled in large part by earlier breakthroughs in biological polymers, most notably DNA sequencing and solid-phase peptide synthesis, which underscored the importance of monomer sequence and primary structure in dictating polymer function. These biological advances also provided methodological frameworks that could be adapted for synthetic systems. The iterative protection–deprotection cycles used in peptide synthesis inspired analogous strategies for abiotic sequence-defined polymers. In a similar vein, automated peptide synthesizers served as inspiration for recent successes in automating syntheses of sequence-defined peptoids and urethanes, among other examples. With numerous methods now available to access monodisperse, precisely designed abiotic polymers with diverse backbones and side chain functionalities, new applications for these compounds are being actively explored. Our group has been particularly interested in developing applications in information storage. As global data storage demands continue to increase, both biotic and abiotic sequence-defined polymers have emerged as promising alternatives to silicon-based technologies due to their high information density, minimal physical footprint, and long-term stability. Drawing on our group’s expertise in chemical sensing, we recognized conceptual parallels between the self-sequencing behavior of self-immolative (or chain-end degrading) polymers and their potential utility in molecular information storage. Chain-end degrading polymers, which depolymerize in response to a single triggering event, inherently encode their structure in a directionally “readable” format, making them attractive scaffolds for encoding, protecting, and later retrieving information, provided that the depolymerization is traceable and the original polymer has a defined sequence. Leveraging these insights, we developed methods to synthesize and analyze sequence-defined oligourethanes. In doing so, we were able to demonstrate that a controlled O → N terminal chain-end degradation occurs via a 5<i>-exo-trig</i> cyclization mechanism in the presence of base and heat, which can be easily monitored by LC/MS. This strategy enables <i>de novo</i> sequencing without reliance on tandem MS, addressing key limitations in the field such as size and complexity of the monomer pool as well as solid-phase synthesis restrictions on polymer chain lengths. With this method we have gone on to encode a number of proof-of-concept pieces of information, including quotes in English and Mandarin, a complex password, and a 256-bit cipher key. We have also leveraged elect
{"title":"The Utility of Chain-End Degradation for De Novo Sequencing of Sequence-Defined Oligourethanes","authors":"Julia R. Shuluk, , , Hazel A. Fargher, , and , Eric V. Anslyn*, ","doi":"10.1021/acs.accounts.5c00900","DOIUrl":"10.1021/acs.accounts.5c00900","url":null,"abstract":"<p >Polymer chemistry has expanded considerably over the past century to include studies of sequence-controlled and sequence-defined polymers. What began as a discipline focused largely on bulk polymer properties, such as mechanical strength, thermal behavior, and processability, has increasingly shifted toward molecular-level precision. These developments were inspired and enabled in large part by earlier breakthroughs in biological polymers, most notably DNA sequencing and solid-phase peptide synthesis, which underscored the importance of monomer sequence and primary structure in dictating polymer function. These biological advances also provided methodological frameworks that could be adapted for synthetic systems. The iterative protection–deprotection cycles used in peptide synthesis inspired analogous strategies for abiotic sequence-defined polymers. In a similar vein, automated peptide synthesizers served as inspiration for recent successes in automating syntheses of sequence-defined peptoids and urethanes, among other examples. With numerous methods now available to access monodisperse, precisely designed abiotic polymers with diverse backbones and side chain functionalities, new applications for these compounds are being actively explored. Our group has been particularly interested in developing applications in information storage. As global data storage demands continue to increase, both biotic and abiotic sequence-defined polymers have emerged as promising alternatives to silicon-based technologies due to their high information density, minimal physical footprint, and long-term stability. Drawing on our group’s expertise in chemical sensing, we recognized conceptual parallels between the self-sequencing behavior of self-immolative (or chain-end degrading) polymers and their potential utility in molecular information storage. Chain-end degrading polymers, which depolymerize in response to a single triggering event, inherently encode their structure in a directionally “readable” format, making them attractive scaffolds for encoding, protecting, and later retrieving information, provided that the depolymerization is traceable and the original polymer has a defined sequence. Leveraging these insights, we developed methods to synthesize and analyze sequence-defined oligourethanes. In doing so, we were able to demonstrate that a controlled O → N terminal chain-end degradation occurs via a 5<i>-exo-trig</i> cyclization mechanism in the presence of base and heat, which can be easily monitored by LC/MS. This strategy enables <i>de novo</i> sequencing without reliance on tandem MS, addressing key limitations in the field such as size and complexity of the monomer pool as well as solid-phase synthesis restrictions on polymer chain lengths. With this method we have gone on to encode a number of proof-of-concept pieces of information, including quotes in English and Mandarin, a complex password, and a 256-bit cipher key. We have also leveraged elect","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"59 6","pages":"958–968"},"PeriodicalIF":17.7,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146778745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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