Accounts of Chemical Research最新文献

{"title":"Nonconventional Luminophores: Emission Mechanism, Regulation, and Applications.","authors":"Zihao Zhao, Anze Li, Wang Zhang Yuan","doi":"10.1021/acs.accounts.4c00794","DOIUrl":"10.1021/acs.accounts.4c00794","url":null,"abstract":"<p><p>ConspectusNonconventional luminophores, characterized by the absence of extended (hetero)aromatic building blocks and alternating single-double/triple bonds, are composed primarily of electron-rich moieties, such as heteroatoms, double bonds, aliphatic amines, carbonyls, hydroxyls, cyano groups, amides, and their grouped functionalities. These unique structural features, coupled with their intriguing luminescent properties, have garnered significant interest for both fundamental research and promising applications, thus enabling widespread exploration. They generally benefit from abundant resources, simple synthesis, outstanding biocompatibility, and excellent photostability, empowering their potential applications in bioimaging, data storage and encryption, anticounterfeiting, bio- and chemosensing, etc. However, their research is preliminary, and the luminescence mechanisms remain elusive. For diverse systems, proposed conjectures, including tertiary amine oxidation, proton transfer, impurities, hydrogen bonding, and peptide bond electron delocalization, lack consistent correlation and universality, with some being subsequently invalidated. This lack of a unifying framework has hampered the development of effective guidelines for molecular design and photoluminescence (PL) regulation. To address these issues, a clustering-triggered emission (CTE) mechanism, focusing on the electron-molecule-aggregate multilevel structure-activity relationships, has been proposed. Specifically, it identifies the \"clustered chromophores\" of electron-rich moieties as emissive species. The CTE mechanism not only elucidates the emission behaviors of diverse nonconventional luminophores but also guides the PL regulation and further development of novel multifunctional luminescent materials.This Account begins with a concise introduction to the proposed CTE mechanism, highlighting the significance of electron delocalization (through-space conjugation) within the \"clustered chromophores\" of electron-rich groups. It then delves into insights gained from various nonconventional luminescent systems, identifying three core components of the CTE mechanism: electron-rich moieties, their clustering, and the conformational rigidity of the resulting clusters. The CTE mechanism proves to be rational and universally applicable, encompassing natural products, (macro)biomolecules, and synthetic compounds and extending from singlet fluorescence to triplet phosphorescence. By strategically coordinating these elements, it is feasible to modulate intra/intermolecular interactions, through-space conjugation, and spin-orbit coupling within the clusters, thus enabling effective PL regulation and achieving red/near-infrared (NIR) room-temperature phosphorescence (RTP) in these systems through both internal/chemical (e.g., incorporating additional bridging units and heavy atoms) and external/physical (e.g., pressurization, conformation adjustments) methods. Furthermore, we investigate","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"612-624"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363159","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}

{"title":"Symmetry Breaking: Case Studies with Organic Cage-Racemates.","authors":"Chenhao Chen, Shaodong Zhang","doi":"10.1021/acs.accounts.4c00754","DOIUrl":"10.1021/acs.accounts.4c00754","url":null,"abstract":"<p><p>ConspectusSymmetry is a pervasive phenomenon spanning diverse fields, from art and architecture to mathematics and science. In the scientific realms, symmetry reveals fundamental laws, while symmetry breaking─the collapse of certain symmetry─is the underlying cause of phenomena. Research on symmetry and symmetry breaking consistently provides valuable insights across disciplines, from parity violation in physics to the origin of homochirality in biology. Chemistry is particularly rich in symmetry breaking studies, encompassing areas such as asymmetric synthesis, chiral resolution, chiral structure assembly, and so on. Across different disciplines, a well-defined methodology is fundamental and necessary to analyze the symmetry or symmetry breaking nature behind the phenomenon, enabling researchers to uncover the underlying principles and mechanisms. Basically, three key points underpin symmetry-related research: the scale-dependency of symmetry/symmetry breaking, the driving force behind symmetry breaking phenomena, and the properties arising from symmetry breaking.This Account will focus on the three aforementioned key points elucidated with organic cages as proof-of-concept models, as organic cages exhibit shape-persistent 3D molecular frameworks, well-defined molecular motion, and a high propensity for crystallization.First, we examine racemization processes of organic cages with dynamic molecular motions to illustrate that symmetry and symmetry breaking are time-scale-dependent. Specifically, the racemization, driven by molecular motion, is influenced by hydrogen bonding and the rigidity of the cage framework, which may or may not be observable within the experimental temporal scale. This determines whether the enantiomeric excess system, namely, the symmetry broken system, can be detected experimentally. We also investigate the hierarchical structures self-assembled by racemic organic cages, demonstrating that symmetry and asymmetry manifest differently across spatial scales, from molecular to supramolecular and macroscopic levels. Second, we discuss the driving force behind spontaneous chiral resolution─a classic symmetry-breaking event during crystallization─from a thermodynamic perspective. We suggest that racemic compounds, compared to conglomerates, are more entropy-favored, explaining their greater prevalence in nature. Spontaneous chiral resolution can take place only when a favorable enthalpy compensates for unfavorable entropy. In conglomerates composed of organic cages, strong intermolecular interactions along the screw axes provide the necessary compensation. Finally, we explore the unique properties that emerge from symmetry-broken molecular packing within crystals of cage racemates, such as second-harmonic generation and piezoelectricity. It turns out that the symmetry operation in molecular packing plays a critical role in determining material properties. By comprehensively analyzing symmetry and symmetry-breaking in organ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"583-598"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050945","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}

{"title":"Near-Infrared-II Fluorescent Probes for Analytical Applications: From <i>In Vitro</i> Detection to <i>In Vivo</i> Imaging Monitoring.","authors":"Sha Liu, Wenhong Dong, Hui-Quan Gao, Zhaorui Song, Zhen Cheng","doi":"10.1021/acs.accounts.4c00671","DOIUrl":"10.1021/acs.accounts.4c00671","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusBiomarkers play a vital role in the regulation of life processes, especially in predicting the occurrence and development of diseases. For the early diagnosis and precise treatment of diseases, it has become necessary and significant to detect biomarkers with sensitivity, accuracy, simplicity, convenience, and even visualization. Fluorescent-probe-based techniques have been recognized as one of the most powerful tools for the sensitive detection and real time imaging of biomarkers in biological samples. However, traditional optical probes, mainly including the visible probes (400-700 nm) and the near-infrared I (NIR-I, 700-900 nm) probes, suffer from low sensitivity, poor resolution, strong absorption and scattering, and high background fluorescence, which hinder effective monitoring of biomarkers.Fortunately, the past decade has witnessed a remarkable evolution in the application fields of near-infrared II (NIR-II, 900-1700 nm) fluorescence, driven by its exceptional optical characteristics and the advancement of imaging technologies. Leveraging the superior penetration capabilities, negligible autofluorescence, and extended fluorescence emission wavelengths, NIR-II fluorescent probes significantly enhance the signal-to-noise ratio (SNR) of &lt;i&gt;in vitro&lt;/i&gt; detection (IVD) and the temporal resolution of &lt;i&gt;in vivo&lt;/i&gt; imaging. Our team has been committed to the design strategy, controlled synthesis, luminous mechanisms, and biomedical applications of NIR-II fluorescent probes. In this Account, we present the representative works in recent years from our group in the field of NIR-II fluorescent probes for analytical applications, ranging from &lt;i&gt;in vitro&lt;/i&gt; detection of biomarkers to &lt;i&gt;in vivo&lt;/i&gt; imaging monitoring of different biomarkers and various diseases, which also will further provide a general overview of analytical applications of NIR-II fluorescence probes. First, the &lt;i&gt;in vitro&lt;/i&gt; analytical applications of NIR-II fluorescent probes are fully summarized, including tumor marker detection, virus and bacteria analysis, cell testing, and small-molecule sensing. Second, the &lt;i&gt;in vivo&lt;/i&gt; imaging monitoring applications of NIR-II fluorescent probes are adequately discussed, including ROS detection, gas monitoring, pH sensing, small-molecule testing, receptor analysis, and the imaging diagnosis of some serious diseases. Finally, we further outline the application advantages of NIR-II fluorescent probes in analytical fields and also discuss in detail some challenges as well as their future development. There is a reasonable prospect that the &lt;i&gt;in vitro&lt;/i&gt; detection technology and the &lt;i&gt;in vivo&lt;/i&gt; imaging monitoring technology based on NIR-II fluorescent probes will exhibit great development potential in biomedical research and clinical disease diagnosis. We hope that this Account can expand their reach into an even broader spectrum of fields, further enhancing their impact on scientific discovery and medical practice.&lt;","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"543-554"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187516","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}

{"title":"Heterogeneous Frustrated Lewis Pair Catalysts: Rational Structure Design and Mechanistic Elucidation Based on Intrinsic Properties of Supports.","authors":"Jiasi Li, Guangchao Li, Shik Chi Edman Tsang","doi":"10.1021/acs.accounts.4c00683","DOIUrl":"10.1021/acs.accounts.4c00683","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusThe discovery of reversible hydrogenation using metal-free phosphoborate species in 2006 marked the official advent of frustrated Lewis pair (FLP) chemistry. This breakthrough revolutionized homogeneous catalysis approaches and paved the way for innovative catalytic strategies. The unique reactivity of FLPs is attributed to the Lewis base (LB) and Lewis acid (LA) sites either in spatial separation or in equilibrium, which actively react with molecules. Since 2010, heterogeneous FLP catalysts have gained increasing attention for their ability to enhance catalytic performance through tailored surface designs and improved recyclability, making them promising for industrial applications. Over the past 5 years, our group has focused on investigating and strategically modifying various types of solid catalysts with FLPs that are unique from classic solid FLPs. We have explored systematic characterization techniques to unravel the underlying mechanisms between the active sites and reactants. Additionally, we have demonstrated the critical role of catalysts' intrinsic electronic and geometric properties in promoting FLP formation and stimulating synergistic effects. The characterization of FLP catalysts has been greatly enhanced by the use of advanced techniques such as synchrotron X-ray diffraction, neutron powder diffraction, X-ray photoelectron spectroscopy, extended X-ray absorption fine structure, elemental mapping in scanning transmission electron microscopy, electron paramagnetic resonance spectroscopy, diffuse-reflectance infrared Fourier transform spectroscopy, and solid-state nuclear magnetic resonance spectroscopy. These techniques have provided deeper insights into the structural and electronic properties of FLP systems for the future design of catalysts.Understanding electron distribution in the overlapping orbitals of LA and LB pairs is essential for inducing FLPs in operando in heterogeneous catalysts through target electron reallocation by external stimuli. For instance, in silicoaluminophosphate-type zeolites with weak orbital overlap, the adsorption of polar gas molecules leads to heterolytic cleavage of the Al&lt;sup&gt;δ+&lt;/sup&gt;-O&lt;sup&gt;δ-&lt;/sup&gt; bond, creating unquenched LA-LB pairs. In a Ru-doped metal-organic framework, the Ru-N bond can be polarized through metal-ligand charge transfer under light, forming Ru&lt;sup&gt;+&lt;/sup&gt;-N&lt;sup&gt;-&lt;/sup&gt; pairs. This activation of FLP sites from the framework represents a groundbreaking innovation that expands the catalytic potential of existing materials. For catalysts already employing FLP chemistry to dynamically generate products from substrates, a complete mechanistic interpretation requires a thorough examination of the surface electronic properties and the surrounding environment. The hydrogen spillover ability on the Ru-doped FLP surfaces improves conversion efficiency by suppressing hydrogen poisoning at metal sites. In situ H&lt;sub&gt;2&lt;/sub&gt;-H&lt;sub&gt;2&lt;/sub&gt;O conditions enable the production ","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"555-569"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050942","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}

{"title":"Microfluidics-Assembled Nanovesicles for Nucleic Acid Delivery.","authors":"Xuanyu Li, Zhiliang Qin, Saijie Wang, Lingmin Zhang, Xingyu Jiang","doi":"10.1021/acs.accounts.4c00738","DOIUrl":"10.1021/acs.accounts.4c00738","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusMicrofluidic technologies have become a highly effective platform for the precise and reproducible production of nanovesicles used in drug and nucleic acid delivery. One of their key advantages lies in the one-step assembly of multidrug delivery nanovesicles, which improves batch-to-batch reproducibility by minimizing the intermediate steps typically required in conventional methods. These steps often involve complex hydrophobic and electrostatic interactions, leading to variability in the nanovesicle composition and performance. Microfluidic systems streamline the encapsulation of diverse therapeutic agents, including hydrophilic nucleic acids, proteins, and both hydrophobic and hydrophilic small molecules, within a single chip, ensuring a more consistent production process. This capability enables the codelivery of multiple drugs targeting different disease pathways, which is particularly valuable in reducing the risk of drug resistance.Despite the promise of nanovesicles for nucleic acid delivery, their clinical translation has been hindered by safety concerns, particularly cytotoxicity, which has overshadowed efforts to improve in vivo stability and delivery efficiency. Positively charged nanovesicles, commonly used to encapsulate negatively charged nucleic acids, tend to exhibit significant cytotoxicity. To address this, charge-shifting materials that respond to pH changes or surface modifications have been proposed as promising strategies. Shifting the surface charge from positive to neutral or negative at physiological pH can reduce the cytotoxicity, enhancing the clinical feasibility of these nanovesicle-based therapies.Microfluidic platforms offer precise control over key nanovesicle properties, including particle size, rigidity, morphology, and encapsulation efficiency. Particle size is relatively easy to adjust by controlling flow rates within microfluidic channels, with higher flow rates generally producing smaller particles. However, continuous tuning of the particle rigidity remains challenging. By manipulation of the interfacial water layer between hydrophobic and amphiphilic components during nanoparticle formation, future designs may achieve greater control over rigidity, which is critical for improving cellular uptake and biodistribution. While shape tuning using microfluidic chips has not yet been fully explored in biomedical applications, advances in materials science may enable this aspect in the future, offering further customization of the nanovesicle properties.The integration of nanovesicle assembly and surface modification within a single microfluidic platform presents challenges due to the differing speeds of these processes. Nanovesicle assembly is typically rapid, whereas surface modifications, such as those involving functional biomolecules, occur more slowly and often require purification steps. Recent advances, such as rotary valve designs and single-axis camshaft mechanisms, offer precise control o","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"570-582"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187511","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}

{"title":"Strategies and Prospects for Engineering a Stable Zn Metal Battery: Cathode, Anode, and Electrolyte Perspectives.","authors":"Kang Zhou, Xiaomeng Yu, Xiaoli Dong, Ziyang Guo, Yonggang Wang","doi":"10.1021/acs.accounts.4c00776","DOIUrl":"10.1021/acs.accounts.4c00776","url":null,"abstract":"&lt;p&gt;&lt;p&gt;ConspectusZinc metal batteries (ZMBs) appear to be promising candidates to replace lithium-ion batteries owing to their higher safety and lower cost. Moreover, natural reserves of Zn are abundant, being approximately 300 times greater than those of Li. However, there are some typical issues impeding the wide application of ZMBs. Traditional inorganic cathodes exhibit an unsatisfactory cycling lifetime because of structure collapse and active materials dissolution. Apart from inorganic cathodes, organic materials are now gaining extensive attention as ZMBs cathodes because of their sustainability, high environmental friendliness, and tunable molecule structure which make them usually exhibit superior cycling life. Nevertheless, due to the inferior conductivity of organic materials, their mass loading and volumetric energy density still cannot meet our demands. In addition, the specific working mechanism of inorganic/organic cathodes also needs further investigation, necessitating the use of advanced in situ characterization technologies. Reversibility of metallic Zn anodes is also crucial in determining the overall cell performances. Like Li and Na anodes, uncontrolled dendrite growth is also an annoying problem for Zn anodes, which may penetrate the separator and cause inner short circuit. In aqueous electrolyte, highly reactive H&lt;sub&gt;2&lt;/sub&gt;O molecules easily attack metallic Zn anode, leading to undesired Zn corrosion. Furthermore, during cell operation, hydrogen evolution reaction (HER) occurs, which leads to continuous consumption of electrolytes and formation of insulating byproducts on Zn anodes. Although strategies like novel Zn anode design and artificial SEI layer construction are proposed to inhibit dendrites growth and protect Zn anodes from active H&lt;sub&gt;2&lt;/sub&gt;O attack, the corresponding manufacturing process remains complex. Modifying electrolyte components is relatively simple to implement and effectively stabilizes Zn anodes. However, HER cannot be completely eliminated when H&lt;sub&gt;2&lt;/sub&gt;O exists in the modified electrolytes. Under such conditions, nonaqueous electrolytes appear to be a promising solution for ZMBs in the future due to their aprotic nature and high stability with the Zn anodes. However, the ionic conductivity of nonaqueous electrolytes is relatively low compared to that of aqueous electrolytes. Most of the previous reviews focus only on the individual components of ZMBs. A review of ZMBs from a higher perspective, focusing on advanced ZMBs system design, is currently lacking.In this Account, we begin with a brief overview of ZMBs, highlighting their advantages and current challenges. Subsequently, we give a summary of the development of inorganic cathodes (such as MnO&lt;sub&gt;2&lt;/sub&gt;) for ZMBs. Specifically, development history and representative modification strategy of inorganic cathodes are illustrated. Following this, representative organic cathodes are discussed, along with introduction of novel modification s","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"599-611"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062103","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}

{"title":"Dibenzothiophenium Salts: Practical Alternatives to Hypervalent I(III)-Based Reagents.","authors":"Manuel Alcarazo","doi":"10.1021/acs.accounts.4c00804","DOIUrl":"10.1021/acs.accounts.4c00804","url":null,"abstract":"<p><p>ConspectusDuring the past few years, the interest among organic synthesis practitioners in the use of sulfonium salts has exponentially growth. This can arguably be attributed to a series of specific factors: (a) The recent development of more direct and efficient protocols for the synthesis of these species, which make sulfonium reagents of a wide structural variety easily available in multigram scale. (b) The recognition that the reactivity of these salts resembles that of hypervalent iodine compounds, and therefore, they can be used as effective replacement of such species in most of their applications. (c) Their intrinsic thermal stability and tolerance to air and moisture, which clearly surpass that of I(III)-reagents of analogue reactivity, and facilitate their purification, isolation as well-defined species, storage, and safely handling on larger scale. (d) Finally, the possibility to further functionalize sulfonium salts once the sulfur-containing platform has been incorporated. Specifically, this last synthetic approach is not trivial when working with hypervalent I(III)-species and facilitates the access to sulfonium salts with no counterpart in the I(III) realm.This renewed interest in sulfonium salts has led to the improvement of already existing transformations as well as to the discovery of unprecedented ones; in particular, by the development of protocols that incorporate sulfonium salts as partners in traditional cross-coupling and C-H activation steps or combine them with more modern technologies such as photocatalysis or electrosynthesis. In this Account, the reactivity of a series of sulfonium salts originally prepared in our laboratory will be outlined and compared to their I(III)-counterparts. Some of these reagents are now commercially available, and their use has started to spread widely across the synthetic chemistry community, helping to speed the process of identification of potentially bioactive products or new functionaliced materials. However, challenges still remain. The development of sulfonium reagents characterized by an optimal balance between reactivity and site-selectivity, or showing broader compatibility toward sensitive functional groups is still a need. In addition, the intrinsic stability of sulfonium salts often makes necessary the use of (sophisticated) catalysts that activate the latent reactivity hidden in their structures. Although <i>a priori</i> one can see this fact as a disadvantage, it might actually be decisive to harvest the full synthetic potential of sulfonium salts because their thermal stability will surely facilitate the preparation of operational reagents with no counterpart in the context of I(III)-chemistry. If this becomes true, sulfonium salts may contribute to the expediting of retrosynthetic disconnections that, to date, are impossible.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"635-646"},"PeriodicalIF":16.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077851","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}

{"title":"Generalizable Molecular Switch Designs for In Vivo Continuous Biosensing","authors":"Jason Saunders,&nbsp;Ian A. P. Thompson and Hyongsok Tom Soh*,&nbsp;","doi":"10.1021/acs.accounts.4c0072110.1021/acs.accounts.4c00721","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00721https://doi.org/10.1021/acs.accounts.4c00721","url":null,"abstract":"&lt;p &gt;Continuous biosensors have the potential to transform medicine, enabling healthcare to be more preventative and personalized as compared to the current standard of reactive diagnostics. Realizing this transformative potential requires biosensors that can function continuously &lt;i&gt;in vivo&lt;/i&gt; without sample preparation and deliver molecular specificity, sensitivity, and high temporal resolution. Molecular switches stand out as a promising solution for creating such sensors for the continuous detection of many different types of molecules. Molecular switches are target-binding receptors designed such that binding causes a conformational change in the switch’s structure. This structure switching induces a measurable signal change via reporters incorporated into the molecular switch, enabling highly specific, label-free sensing. However, there remains an outstanding need for generalizable switch designs that can be adapted for the detection of a wide range of molecular targets.&lt;/p&gt;&lt;p &gt;In this Account, we chronicle the work our lab has done to develop generalizable molecular switch designs that allow more rapid development of high-performance biosensors across a broad range of biomarkers. Pioneering efforts toward molecular switch-based biosensing have employed aptamers─nucleic acid-based receptors with sequence-specific target affinity. However, most of these early demonstrations relied upon aptamers with intrinsic structure-switching capabilities. To accelerate aptamer switch design for more targets, we have applied rational design and knowledge of an aptamer’s structure to engineer switching functionality into pre-existing aptamers. Our designs contained several structural parameters that enabled us to easily tune the sensitivity and binding kinetics of the resulting switches. Using such rationally designed aptamer switches, we demonstrated continuous optical detection of cortisol and dopamine at physiologically relevant concentrations in complex media. In an effort to move beyond aptamers with well-characterized structural properties, we developed a high-throughput screening method that allowed us to simultaneously screen millions of candidates derived from a single aptamer to find sensitive switches without any prior structural knowledge of the parent aptamer.&lt;/p&gt;&lt;p &gt;In subsequent work, we reasoned that we could enhance our ability to design a broader range of biosensors by leveraging other classes of receptors besides aptamers. Antibodies offer excellent affinity and specificity for a wide range of targets, but lack the capacity for intrinsic structure switching. We therefore developed a set of strategies to augment antibodies with the capacity to act as molecular switches with a diverse range of target-binding properties. We combined both the high binding affinity of an antibody with the structure-switching capabilities of an aptamer to develop a chimeric switch with 100-fold enhanced sensitivity for a protein target and improved function in","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 5","pages":"703–713 703–713"},"PeriodicalIF":16.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.accounts.4c00721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533643","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}

{"title":"Generalizable Molecular Switch Designs for In Vivo Continuous Biosensing","authors":"Jason Saunders, Ian A. P. Thompson, Hyongsok Tom Soh","doi":"10.1021/acs.accounts.4c00721","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00721","url":null,"abstract":"Continuous biosensors have the potential to transform medicine, enabling healthcare to be more preventative and personalized as compared to the current standard of reactive diagnostics. Realizing this transformative potential requires biosensors that can function continuously <i>in vivo</i> without sample preparation and deliver molecular specificity, sensitivity, and high temporal resolution. Molecular switches stand out as a promising solution for creating such sensors for the continuous detection of many different types of molecules. Molecular switches are target-binding receptors designed such that binding causes a conformational change in the switch’s structure. This structure switching induces a measurable signal change via reporters incorporated into the molecular switch, enabling highly specific, label-free sensing. However, there remains an outstanding need for generalizable switch designs that can be adapted for the detection of a wide range of molecular targets.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"56 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418273","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}

{"title":"Designing Functional and Responsive Molecules with Boronic Acids","authors":"João P. M. António,&nbsp;Inês L. Roque,&nbsp;Fábio M. F. Santos and Pedro M. P. Gois*,&nbsp;","doi":"10.1021/acs.accounts.4c0069110.1021/acs.accounts.4c00691","DOIUrl":"https://doi.org/10.1021/acs.accounts.4c00691https://doi.org/10.1021/acs.accounts.4c00691","url":null,"abstract":"<p >Boronic acids (BAs) are one of the most important classes of reagents in modern synthesis, enabling a wide range of powerful transformations that facilitate the formation of key carbon–carbon and carbon–heteroatom bonds. While their success as reagents is well-known, their remarkable potential as building blocks for creating functional molecules is often overlooked.</p><p >At the core of BAs’ uniqueness is their ability to form reversible covalent bonds, thanks to the interconversion of the boron atom between its uncharged trigonal planar structure and an anionic sp³-hybridized form. This coordination chemistry has paved the way for exciting developments in fields such as medicinal chemistry and chemical biology. In recent years, BAs have been used to create a wide variety of materials, including small-molecule drugs, bioconjugates, drug delivery vehicles, polymeric nanomaterials, sensors, and even photosensitizers. What makes this strategy particularly unique is the structural diversity that can be achieved by functionalizing the BA coordination sphere, along with the possibility of incorporating stimuli-responsive mechanisms. This reactivity is further enhanced by the well-known oxidation of BAs in the presence of reactive oxygen species (ROS).</p><p >A detailed understanding of the mechanisms governing the dynamic nature of BAs enables the engineering of sophisticated materials that can respond to specific molecular stimuli, such as changes in pH, carbohydrate or glutathione concentrations, and hydrogen peroxide. These stimuli are often key indicators of diseases such as cancer, inflammation, and neurodegeneration, placing BAs at the forefront of tools for designing materials that can potentially influence the mechanisms behind these diseases.</p><p >In this Account, we draw on our group’s expertise to explore the exciting potential of BAs in the design of functional materials. The focus is on the response of different boron complexes to biologically relevant stimuli. We describe the preparation of boronated esters (BEs), BA–salicylhydroxamic acid (BA–SHA) complexes, iminoboronates, diazaborines, and boronated thiazolidines and discuss how these chemotypes respond to disease-relevant triggers. Given the growing importance of using external stimuli to control the efficacy of modern drugs, we also explore how some of these compounds respond to specific chemicals. While this Account is not meant to be an exhaustive survey of every example of BA stimulus-responsiveness, we aim to integrate existing chemotypes and their chemical triggers. Our goal is to provide an overview of the mechanisms enabled by BAs for designing functional materials that could one day lead to innovative therapeutic options for human diseases.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 5","pages":"673–687 673–687"},"PeriodicalIF":16.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533696","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}