Lela K. Manis, Jiankai Ge, Changhae Andrew Kim, Emmanuel Ejiogu, Ziqiu Chen, Ryan D. Yappert and Baron Peters*,
{"title":"","authors":"Lela K. Manis, Jiankai Ge, Changhae Andrew Kim, Emmanuel Ejiogu, Ziqiu Chen, Ryan D. Yappert and Baron Peters*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 12","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":16.4,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144343167","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":"The Chemistry Behind and Beyond the Molecular Engineering of 1,7-Naphthiporphyrin","authors":"Min-Sung Ko, Dong-Gyu Cho","doi":"10.1021/acs.accounts.5c00301","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00301","url":null,"abstract":"The discovery of 1,7-naphthiporphyrin was based on a specific naphthalene connectivity that disrupts naphthalene’s local aromaticity, and its global aromaticity was experimentally confirmed without dispute. Its unique conjugated pathways inspired our molecular engineering approaches─an unprecedented strategy for modifying the core structure of porphyrinoids. The first synthesis of <i>o</i>-styreniporphyrin was achieved in a truncated form, and further truncation yielded allyliporphyrin. Both compounds exhibited dynamic behavior in solution, including observable vinylenic bond rotation. Similarly, 1,7-naphthiporphyrin was converted into naphthioxacorrole by removing one <i>meso</i>-like carbon; its oxidized form featured an enedione unit that underwent selective sulfur or nitrogen nucleophilic addition, accompanied by color change. To obtain a larger macrocycle, we synthesized dimeric forms of 1,7-naphthiporphyrin, which exhibited a conjugation pathway approximating a 22π system (although a 34π system is also possible). As another possible approach, the naphthalene moiety of 1,7-naphthiporphyrin was expanded to anthracene, whose central ring acted as a diene and reacted with DMAD (a dienophile) to yield a new phlorin structure. Similarly, <i>o</i>-styreniporphyrin was expanded with naphthalene and anthracene; interestingly, its aromaticity decreased with increasing polycyclic aromatic hydrocarbon (PAH) size. Its aromaticity was evaluated by analyzing conformers and tautomers at equilibrium and considering their calculated energy levels. Functionalized allyliporphyrins were used to address an unresolved question in physical science: do electron-donating (ED) or electron-withdrawing (EW) groups reduce aromaticity? Allyliporphyrins─which offer more space at one <i>meso</i>-like position due to the partial removal of the naphthalene unit and the presence of both inner and outer CH groups─facilitated the evaluation of global aromaticity upon ED or EW substitution. Our experiments support the conclusion that both ED and EW groups reduce aromaticity. We then examined whether Clar’s sextets always contradict resonance theory. Some porphyrinoids derived from 1,7-naphthiporphyrin contain PAHs that allow the identification of two distinct Clar’s sextets─shared and independent─relative to the global conjugated pathway. To enable direct comparison, regioisomers of <i>o</i>-vinylnaphthiporphyrins were synthesized using our synthetic strategy. Sextet analysis of three regioisomers predicted that 3,4-vinylnaphthiporphyrin is the most aromatic (with an independent sextet), 1,2-vinylnaphthiporphyrin is next (with an independent sextet but some steric hindrance between thiophene and naphthalene), and 2,3-vinylnaphthiporphyrin is the least aromatic or nearly nonaromatic (with shared sextets). This ordering, along with other examples, verifies that an independent sextet stabilizes the global conjugation pathway, whereas shared sextets destabilize it. Overall, the modi","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"12 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305359","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":"Molecular Gridization of Organic Semiconducting π Backbones","authors":"Tonglin Yang, Yanwei Tang, Ying Wei, Linghai Xie, Wei Huang","doi":"10.1021/acs.accounts.5c00180","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00180","url":null,"abstract":"Organic π-conjugated molecules and polymers have emerged as some of the most promising candidates of semiconductors for future information, intelligent technology, and smart manufacturing because of their unique properties such as structural diversity, flexibility, stretchability, ultrathinness, light weight, low-cost and large-area fabrication procedures, and excellent biocompatibility. However, several severe challenges remain, including inferior optical and electronic properties compared to inorganic materials, poor stability and lifespan, low yields in solution processing patterning techniques, inadequate mechanical endurance, and difficulties in multifunctionalization. Particularly, there are still no big breakthroughs in terms of the common and long-term challenges, such as flexible organic light-emitting diodes (OLEDs) with printing procedures that could not be achieved at the calibration of commercialization, electrically pumped lasers that become the open global question, and organic integrated circuits and brain-like computing technologies at the conceptual stage. The nanosization of the molecular π systems is one crucial way to address the dilemmas that stem from the molecular limitation of organic semiconductors. Covalent nanoscale strategies of organic semiconducting π backbones enable not only effective suppression of phonon behavior, thereby significantly improving their charge transport capacity and exciton efficiency, but also facilitate functional integration for intelligent semiconductors.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"148 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288578","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":"Bioinspired Chiral Peptide–Phosphonium Salt Catalysis: From Enzymes to Cationic Small-Molecule Enzyme Mimics","authors":"Siqiang Fang, Zanjiao Liu, Fan Wang, Tianli Wang","doi":"10.1021/acs.accounts.5c00257","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00257","url":null,"abstract":"Enzymes exemplify nature’s catalytic mastery through precise stereochemical control and remarkable rate enhancements, yet their synthetic application remains limited by inherent vulnerabilities: thermal instability, narrow substrate tolerance, and complex engineering requirements. These challenges drive our pursuit of modular organocatalysts that emulate enzymatic cooperativity while combining ease of synthesis, versatility, and high tunability, termed “bioinspired organic small-molecule enzymes”.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"44 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144288612","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":"Emerging Capabilities of Nonclassical Noncovalent Interactions and Asymmetric Catalysis in Stereoselective Glycosylations and Carbohydrate Functionalizations","authors":"Amal Tom Sebastian, Charles C. J. Loh","doi":"10.1021/acs.accounts.5c00289","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00289","url":null,"abstract":"Deriving inspiration from frontier catalytic paradigms has emerged as a major force to tackle long-standing stereoselectivity issues in carbohydrate synthesis. In particular, there is a strong momentum in the harnessing of <b><i>nonclassical σ-hole based noncovalent interactions (NCIs) in chemical glycosylations</i></b> and the use of <b><i>asymmetric catalysis to surmount the formidable site-selectivity challenge</i></b> in the functionalization of carbohydrate polyols.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"12 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269456","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":"Fluorinated Radicals in Divergent Synthesis via Photoredox Catalysis","authors":"Rahul Giri, Anthony J. Fernandes, Dmitry Katayev","doi":"10.1021/acs.accounts.5c00239","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00239","url":null,"abstract":"Fluorine is an essential element in pharmaceuticals, agrochemicals, and material sciences, significantly enhancing the bioactivity, metabolic stability, and physicochemical properties of organic molecules. In medicinal chemistry, nearly 20% of marketed drugs contain at least one fluorine atom within their core structure. Despite its widespread importance, naturally occurring organofluorine compounds are exceedingly rare, necessitating the development of productive synthetic strategies for fluorine incorporation. The majority of fluorination protocols at the industrial level rely on reagents made from highly reactive and hazardous hydrogen fluoride (HF) or elemental fluorine (F<sub>2</sub>), which present substantial challenges in handling and safety at the laboratory scale. Moreover, considerations of cost, availability, and synthetic performance have led to a renewed interest in utilizing readily accessible, bulk-manufactured compounds such as fluorinated acids and anhydrides. The activation of these redox-active reagents presents a promising avenue to achieve selective, efficient, and sustainable fluoroalkylation reactions.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"10 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269455","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":"Regulating Bacteria–Host Interactions for Disease Intervention by Covalent Conjugation of Bacterial Surface","authors":"Mian Chen, Jinyao Liu","doi":"10.1021/acs.accounts.5c00271","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00271","url":null,"abstract":"The interactions between bacteria and in vivo environments are critical for microorganism-host association, which plays essential roles in host immunomodulation and nutrient metabolism. Regulating the interactions of bacteria with various in vivo interfaces can vary microorganism-host relationships, offering a promising approach to intervene immune and/or metabolism disorders. However, the rationale behind the modulation of bacterial interactions with surroundings is poorly understood and methods capable of modifying bacteria to tune the crosstalk with the host have been rarely reported. Recently, considerable attention has been paid to bacterial surface modification, where bacteria can be incorporated with diverse exogenous components. Among different modification strategies, surface conjugation based on covalent chemical linkages has emerged as a key tool to design and introduce functional motifs. Particularly, surface covalent conjugation (SCC) allows for stable attachment of active components to specific sites on bacteria with molecular-level specificity and selectivity, providing a solid foundation for precisely regulating bacterial interactions with in vivo environments.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"17 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252623","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":"Flexible Metal–Organic Frameworks for Adsorptive Separation of Liquid Hydrocarbons","authors":"Feng Xie, Hao Wang, Jing Li","doi":"10.1021/acs.accounts.5c00217","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00217","url":null,"abstract":"The separation and purification of liquid hydrocarbons are vital for producing various petrochemical feedstocks. However, the structural and chemical similarities among these hydrocarbons make conventional separation methods such as distillation and extraction both challenging and energy intensive. Adsorptive separation using porous solid adsorbents presents a promising and energy-efficient alternative. Among these, flexible metal–organic frameworks (FMOFs) as a subgroup of MOFs have emerged as an unparalleled class of porous materials for highly selective adsorption-based separation and purification of liquid hydrocarbons. Having intrinsically dynamic structures, FMOFs exhibit very different adsorption behaviors compared to rigid MOFs (RMOFs), those that do not involve structure transformations upon activation, and molecular adsorption.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"216 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252628","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":"Hydrogen Atom Transfer Promoted by Carbon-Centered Biradicals via Energy Transfer Catalysis","authors":"Ben Mao, Jun Yan, Yin Wei, Min Shi","doi":"10.1021/acs.accounts.5c00228","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00228","url":null,"abstract":"In the past decade, visible-light-mediated photocatalysis has emerged as an applicable strategy for the generation of diverse radical species via single electron transfer (SET) and energy transfer (EnT) processes. Within this context, visible-light-mediated hydrogen atom transfer (HAT) has attracted major interest due to its mild and environmentally benign conditions applied in the selective activation of C–H bonds. Strategies employing C- and heteroatom-centered radical species to selectively activate C–H bonds have become versatile tools due to their mildness and good functional group compatibility for synthesizing value-added products. In this regard, a review on C-centered radical-promoted HAT processes was reported by Gevorgyan’s group ( <cite><i>Chem. Sci.</i></cite> <span>2020</span>, <em>11</em>, 12974, DOI: 10.1039/d0sc04881j), and a review on visible-light-promoted remote C–H functionalization via 1,5-HAT was recently reported by Zhu’s group ( <cite><i>Chem. Soc. Rev.</i></cite> <span>2021</span>, <em>50</em>, 7359, DOI: 10.1039/d0cs00774a). Compared to N- and O-centered radical-promoted HAT processes, C(sp<sup>3</sup>)-centered radical-promoted HAT is more challenging and less explored due to the small differences in C–H bond dissociation energies. Additionally, in the realm of C-centered radical-promoted HAT, the generation of C-centered radicals has mostly involved SET processes, while the EnT-mediated C-centered radical-promoted HAT process has been less discussed because of the considerable scarcity of related reports.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"7 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252602","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":"Nucleic Acid Nanocapsules as a New Platform to Deliver Therapeutic Nucleic Acids for Gene Regulation","authors":"Suman Pal, Jenna N. Cannata, Jessica L. Rouge","doi":"10.1021/acs.accounts.5c00126","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00126","url":null,"abstract":"Therapeutic nucleic acids have shown enormous potential to treat a vast number of diseases, ranging from cancers to inflammatory diseases. siRNA formulated within lipid nanoparticles (LNPs) achieved FDA approval for a rare liver disorder in 2018, followed shortly after by successful application of mRNA formulated in LNPs in 2020 to stave off a worldwide pandemic. Thus, in only a few short years, interest in nucleic acid drugs has skyrocketed, both within the academic world and the pharmaceutical industry. Despite the excitement surrounding these genetically encodable medicines, there remains much work to do to enable them to be as far reaching of a drug class as they have the potential to be. The major roadblock limiting their clinical potential is the inability of formulations to efficiently deliver nucleic acid cargo to the cytosol of cells, largely due to endosomal entrapment. Additionally, there are challenges associated with the ability of formulations to target nucleic acids to specific cells and subcellular locations. Here, we describe how our lab has been working to address many of these challenges using a new chemical formulation that is distinctly different from traditional liposomes and LNPs, built from the bottom up to specifically enable endosomal escape of its nucleic acid cargo. We took direct inspiration from viruses with the goal of imitating their dynamic design that changes in response to binding and internalization into cells, enabling them to release their genetic cargo into the cytosol by locally disrupting membranes all while maintaining the cells overall integrity.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"3 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252627","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}