Accounts of Chemical Research最新文献

{"title":"Antioxidants: The Chemical Complexity Behind a Simple Word.","authors":"Annia Galano","doi":"10.1021/acs.accounts.5c00552","DOIUrl":"https://doi.org/10.1021/acs.accounts.5c00552","url":null,"abstract":"ConspectusWhat does the word antioxidant mean? Antioxidants are supposed to be nontoxic, versatile molecules capable of counteracting the damaging effects of oxidative stress (OS). Thus, when evaluating a candidate molecule as an antioxidant, several aspects should be considered. Antioxidants are more than free radical scavengers. Other routes may contribute to their protection against OS, including modulation of the redox enzymatic system, preventing free radical formation, and repairing oxidized biomolecules. However, molecules intended as antioxidants can also exhibit pro-oxidant or toxic effects. Thus, understanding the full complexity of their chemistry is crucial for making reliable predictions about their activity.This Account focuses on computational tools that can assist in addressing such a challenging task. Some key aspects to consider when evaluating the potential antioxidant activity (AOX) of a molecule using these tools are (i) its absorption, distribution, metabolism, and excretion (ADME) properties; (ii) the effects of solvent and pH on its speciation and reactivity; and (iii) the toxicity of the molecule, its metabolites, and the products of the reactions it may undergo in vivo. While computational tools offer unique insights into the chemoprotective effects of antioxidants, care must be taken when assessing the data they produce. For example, reactivity descriptors alone are seldom enough to make reliable predictions on AOX. The thermodynamics and kinetics of the reaction pathways contributing to it frequently rule the antioxidant performance. The selected method of calculation should be reliable for the task at hand, since it influences the numerical outcome. Using some references for comparison allows adding context to the calculated data.We have developed two protocols that can be combined to include those aspects into computational studies of antioxidants: the Quantum Mechanics-Based Test for Overall Free Radical Scavenging Activity (QM-ORSA) and the Computer-Assisted Design of Multifunctional Antioxidants Based on Chemical Properties (CADMA-Chem). Some examples of the application of these protocols are discussed herein. They illustrate the diversity of reaction mechanisms and environmental conditions that modulate AOX, considering potential benefits and risks. These protocols provide a theoretical framework for investigating AOX that allows straightforward comparison with experimental results. They can be applied to known antioxidants for gaining insight into observed behavior as well as in the development of new antioxidants intended as potential drug candidates for the treatment of OS-related diseases.This work aims to promote comprehensive investigations into antioxidant chemistry, contribute to the interpretation of the results obtained from calculations, and encourage the development of safe, efficacious molecules that ameliorate the harmful effects of OS on human health.","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"31 1","pages":""},"PeriodicalIF":18.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031795","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":"Hydroaminoalkylation: A Tool of Choice for the Catalytic Addition of Amines to Alkenes in Small Molecules and Materials","authors":"Saeed Ataie,&nbsp; and ,&nbsp;Laurel L. Schafer*,&nbsp;","doi":"10.1021/acs.accounts.5c00375","DOIUrl":"10.1021/acs.accounts.5c00375","url":null,"abstract":"<p >Hydroaminoalkylation, the catalytic addition of amines to alkenes, has evolved as a powerful tool in modern synthetic chemistry, offering an atom-economic and green approach to the construction of C–C bonds. This reaction enables the direct amine functionalization of alkenes and alkynes without the need for protecting groups, directing groups, or prefunctionalization, thereby eliminating stoichiometric waste and minimizing synthetic steps. Over the past two decades, significant advances in catalyst development and mechanistic understanding have expanded the scope of hydroaminoalkylation, allowing for control over regio-, diastereo-, and enantioselectivity. In this Account, we provide a comprehensive overview of our contributions to this field, from fundamental mechanistic insights into early transition metal catalysis to the rational design of hydroaminoalkylation catalysts for small molecule and polymer functionalization. We discuss key breakthroughs, including the development of N,O-chelated early transition metal catalysts, and the use of hydroaminoalkylation in synthesis by providing direct access to valuable α- and β-alkylated amines that serve as key building blocks in pharmaceuticals, agrochemicals, and fine chemicals. The practical applications of hydroaminoalkylation extend beyond small molecule synthesis to the field of polymer chemistry, where it enables both pre- and postpolymerization amination strategies. These advances have unlocked new applications in materials science, particularly in the design of self-healing polymers, adhesives, antibacterial coatings, and polymeric binders for energy storage applications. Additionally, we demonstrate the compatibility of hydroaminoalkylation with other catalytic methods in both small molecule synthesis and polymer chemistry. Finally, we highlight remaining challenges and future opportunities, such as the development of earth-abundant metal catalysts, enantioselective hydroaminoalkylation strategies, and advanced polymer applications. By bridging the gap between small molecule synthesis and polymer chemistry, hydroaminoalkylation shows much promise as a transformative strategy for modern catalysis.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"2956–2969"},"PeriodicalIF":17.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145025895","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":"Quinoline as a Photochemical Toolbox: From Substrate to Catalyst and Beyond","authors":"Jianbin Li*,&nbsp; and ,&nbsp;Chao-Jun Li*,&nbsp;","doi":"10.1021/acs.accounts.5c00513","DOIUrl":"10.1021/acs.accounts.5c00513","url":null,"abstract":"&lt;p &gt;Molecular photochemistry, by harnessing the excited states of organic molecules, provides a platform fundamentally distinct from thermochemistry for generating reactive open-shell or spin-active species under mild conditions. Among its diverse applications, the resurgence of the Minisci-type reaction, a transformation historically reliant on thermally initiated radical conditions, has been fueled by modern photochemical strategies with improved efficiency and selectivity. Consequently, the photochemical Minisci-type reaction ranks among the most enabling methods for C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)–H functionalizations of heteroarenes, which are of particular significance in medicinal chemistry for the rapid diversification of bioactive scaffolds. A persistent challenge, however, lies in the efficient generation of radicals and controllable addition to the electron-deficient heteroaromatic systems. In our pursuit of protocols to overcome these limitations, we unexpectedly uncovered the photochemical potential of quinoline, which is a naturally abundant, synthetically accessible, and structurally versatile heteroaromatic scaffold that has long served as a prototypical substrate in Minisci-type chemistry. Guided by this serendipitous insight and our scientific curiosity, we successfully repurposed quinoline and its derivatives not merely as substrates but also as a versatile and systematic photochemical toolbox capable of participating in, mediating, and ultimately catalyzing a broad spectrum of radical transformations beyond Minisci-type reactions.&lt;/p&gt;&lt;p &gt;This Account weaves together our decade-long research program with several interrelated directions that demonstrate quinoline’s photosynthetic versatility and adaptability. Our exploration began with the photochemical Minisci-type alkylation of quinolines using alkyl radicals generated via various approaches, highlighting this heterocycle’s capacity as a robust radical acceptor for direct C(&lt;i&gt;sp&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt;)–H functionalization of drug-like compounds. This foundational success prompted a deeper inquiry into quinoline’s redox behaviors under direct excitation, wherein we discovered its dual ability to engage its own scaffold to form radical intermediates from otherwise challenging precursors while simultaneously partaking in the Minisci-type alkylation as a classic reaction partner. Armed with this insight, we further developed quinoline derivatives that undergo direct photolysis to release alkyl radicals from their structures. Such a design shifts the role of quinolines from passive substrates to photoactive reagents, thereby enabling greater flexibility in the substrate and reaction scope beyond Minisci-type chemistry and expanding the mechanistic space available for radical-based transformations. Progressing toward catalysis, the extended conjugation and redox tunability of diarylquinoline scaffolds guided our design of organophotocatalysts featuring the unique proton- and photon-activation mo","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3081–3095"},"PeriodicalIF":17.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018055","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":"Unlocking Hydrogen Spillover: Dynamic Behavior and Advanced Applications","authors":"Kazuki Shun,&nbsp; and ,&nbsp;Kohsuke Mori*,&nbsp;","doi":"10.1021/acs.accounts.5c00501","DOIUrl":"10.1021/acs.accounts.5c00501","url":null,"abstract":"<p >Hydrogen spillover, the simultaneous diffusion of protons and electrons, has recently emerged as a key phenomenon in the functionalization of hydrogen in cutting-edge research fields. Its occurrence has been found to significantly impact hydrogen-related fields of science, such as catalysis, reduction, and hydrogen storage. Since the discovery of hydrogen spillover more than half a century ago, although many scientists have reported its unique properties and have attempted to utilize them, no practical advanced applications have been established yet. The biggest issue in realizing such applications is unraveling how spilled atomic hydrogen behaves. Although observation techniques have greatly improved in recent years, a comprehensive understanding of the behavior of spilled hydrogen, such as which pathways it follows and at what temperature it occurs, has not yet been achieved. This is because its behavior can vary depending on the characteristics of the platform materials. Uncovering the dynamics of the hydrogen spillover phenomenon is expected to pave the way toward the creation of new and versatile hydrogen-handling technologies.</p><p >In this Account, we report the comprehensive dynamic behavior of spilled hydrogen on various platform materials and potential advanced applications. For reducible metal oxides, which are the ideal platform for hydrogen spillover, the diffusion pathway for spilled hydrogen is found to depend on the platform material. For TiO₂ and CeO₂, the preferential diffusion pathway is along the surface, whereas for WO₃ it is through the bulk region. For graphene oxide, the ether groups generated by calcination in air enable energetically feasible hydrogen spillover on its basal plane. In the case of MgO, a moderate amount of Al doping provides abundant hydrogen spillover pathways within the bulk of the material.</p><p >Hydrogen spillover induces a strong reduction field on the surface of platform materials, leading to simultaneous reduction of metal ions with different redox potentials. This facilitates the fabrication of nonequilibrium alloy nanoparticles composed of two types of elements with a positive mixing enthalpy, such as Ru–Ni and Rh–Cu. This strategy can be applied to multiple kinds of metal ions and enables the facile synthesis of high-entropy alloy nanoparticles, which exhibit unique catalytic properties. This review establishes guidelines for utilizing the material-dependent behavior of hydrogen spillover and describes advanced applications.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 19","pages":"3060–3070"},"PeriodicalIF":17.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022477","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":"Stabilization of Native Protein–Protein Interactions with Molecular Glues: A 14-3-3 Case Study","authors":"Markella Konstantinidou,&nbsp;Johanna M. Virta and Michelle R. Arkin*,&nbsp;","doi":"10.1021/acs.accounts.5c00441","DOIUrl":"10.1021/acs.accounts.5c00441","url":null,"abstract":"&lt;p &gt;Protein–protein interactions (PPIs) play a key role in homeostasis and are often dysregulated in disease. PPIs were traditionally considered “undruggable” due to their flat surfaces and disordered domains. Recently, the identification of PPI stabilizers, or molecular glues (MGs), compounds that bind cooperatively to PPI interfaces, has provided a new direction for the field. MGs offer exciting opportunities for chemical biology and drug discovery, particularly for intrinsically disordered domains. To date, many of the fascinating MGs were discovered serendipitously, and their molecular glue mechanism of action was understood retrospectively. Our collaborative contribution has been the development of systematic, rational approaches for the identification, optimization, and validation of MGs.&lt;/p&gt;&lt;p &gt;This Account focuses on the modulation of the native PPIs between the hub protein 14-3-3 and its client proteins. 14-3-3 recognizes specific phospho-serine/threonine motifs on disordered domains of hundreds of clients and, depending on the phospho site, can activate or inhibit signaling pathways. Until recently, only the natural product fusicoccin A and its analogs were known to bind at the structured 14-3-3/client interfaces and modulate cellular pathways. The complexity of the natural products significantly hindered chemical biology approaches and did not provide sufficient insight into the systematic, selective targeting of the client of interest.&lt;/p&gt;&lt;p &gt;Inspired by the natural products, we used fragment-based screens to identify new chemical matter for 14-3-3/client PPIs. Using disulfide-tethering technology, we targeted either engineered cysteines on 14-3-3 or the native cysteine (C38) on 14-3-3σ. Five clients (ERα, C-RAF, FOXO1, USP8, and SOS1), representing varying sequences, binding modes, and physiological roles, were included in the initial screens. We identified both selective and nonselective fragments suitable for medicinal chemistry optimization.&lt;/p&gt;&lt;p &gt;Starting from a fragment that stabilized two 14-3-3 clients, estrogen receptor α (ERα) and C-RAF, we developed cell-active MGs selective for ERα. ERα is a well-validated target in breast cancer, and 14-3-3 is a negative regulator that blocks ERα transcriptional activity. We used structure-guided design to optimize ligand–protein interactions at the composite PPI surface. The molecular glues were validated in biophysical assays, including intact mass spectrometry (MS) and fluorescence anisotropy (FA) assays, allowing the quantification of binding, kinetics, and cooperativity.&lt;/p&gt;&lt;p &gt;We explored alternative strategies for the identification and optimization of MGs. For the 14-3-3/ERα complex, we demonstrated fragment linking to generate non-covalent stabilizers and a scaffold-hopping approach using multicomponent reaction chemistry. For the 14-3-3/C-RAF complex, we used a fragment-merging approach to selectively stabilize the inhibited state of C-RAF. Binding of 14-3-3 to the inhibitory p","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":"58 18","pages":"2840–2851"},"PeriodicalIF":17.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.accounts.5c00441","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995999","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":"A Giant Fronto-Ethmoidal Osteoma Presenting With Proptosis and Diplopia.","authors":"Derya Guclu, Emine Izgi, Elif N Unlu, Hayri Ogul","doi":"10.1177/01455613221141220","DOIUrl":"10.1177/01455613221141220","url":null,"abstract":"<p><p>Osteomas are benign bone tumors commonly involving paranasal sinus walls. They are divided into three groups as ivory, mature, and mixed form. We reported demonstrative radiological features of an unusual case of giant osteoma presenting with proptosis and diplopia.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"NP572-NP574"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40702797","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":"Drain-Less Submandibular Gland Excision With Preserved Facial Artery.","authors":"Ahmed Nofal, Mohammad Waheed El-Anwar, Mohamed A Al Shawadfy, Yasser Ahmed Fouad","doi":"10.1177/01455613221142735","DOIUrl":"10.1177/01455613221142735","url":null,"abstract":"<p><p>ObjectivesTo describe our experience in excision of the submandibular gland (SMG) without drain insertion and with preservation of the facial artery as a day case surgery as well as evaluation of the surgical outcomes of this procedure.MethodsProspective case series study of 42 cases of chronic calcular submandibular sialadenitis that underwent SMG excision by the same surgical team during the period from 2017 to 2021. The initial surgical plan in all cases was to excise the SMG with preservation of the facial artery and without drain insertion.ResultsSMG excision without drain insertion was successfully achieved in 28 patients who were discharged on the same day. In the remaining 14 patients, the surgical dissection was difficult and a suction drain was inserted at the end of the surgery; consequently, they were discharged on the next day. In all cases, facial vessels were preserved, and complete gland excision was achieved. Among the 28 patients who had no drain insertion, 1 patient had a postoperative seroma and no patient had wound related complications. Among the 14 patients who had drain insertion, 2 patients had postoperative seroma and 3 patients had wound related complications in the form of obvious scar formation. There were no other significant complications in all patients.ConclusionsSubmandibular gland (SMG) excision with facial artery preservation and without drain insertion as a day case surgery could be safely done in cases of chronic calcular inflammation provided that meticulous surgical dissection and complete hemostasis were achieved.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"559-563"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40714115","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":"Interprofessional identity in clinicians: A scoping review.","authors":"Angela Wood, Jodie Copley, Anne Hill, Neil Cottrell","doi":"10.1080/13561820.2022.2086222","DOIUrl":"10.1080/13561820.2022.2086222","url":null,"abstract":"<p><p>Interprofessional collaborative practice (IPCP) has been recognized as invaluable in delivering safe, high-quality patient care with finite resources. However, despite a decade of advances in interprofessional (IP) research, policy, and competency frameworks, IPCP does not always occur in practice. One reason may be the influence of a clinician's identity in an IP context. The purpose of this scoping review was to understand the nature of IP identity in healthcare clinicians. The PRISMA framework was used to support a comprehensive search strategy and screening of 1746 articles. Inclusion criteria included original research, theses, and reviews, a primary focus on IP identity or professional identity (PI) in an IP team, and a focus on health professionals, including students transitioning to practice. Ninety-five papers met the eligibility criteria, though once charted, just four of the 95 papers focused on IP identity in clinicians. Three further papers examined shared team identity, 25 papers referred to, but did not focus on IP identity, and the remaining 63 papers explored PI in an IP team. While limited studies on clinician IP identity restrict conclusive findings, patterns were identified to direct further research on the nature of IP identity in clinicians. These include values and beliefs, individual and personal factors, profession and professional experience, education, socialization, context, leadership, and the process of IP identity development. While identity is undeniably central to being a clinician, the values, beliefs, attributes, and experiences that contribute to clinician IP identity, how clinician IP identity develops, and factors that influence IP identity remain unclear. The results of this review highlight the value of further investigation of the nature of IP identity, the interplay between PI and IP identity, and identity in an IP context.</p>","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"871-882"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40540194","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":"Tapia's Syndrome: Clinical Insights.","authors":"Ersilia Ruggiero, Alessandro Vergari, Fabio Sbaraglia, Michelangelo Mario Spanò, Rossano Festa, Marco Rossi","doi":"10.1177/01455613221140294","DOIUrl":"10.1177/01455613221140294","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"538-539"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40482864","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":"Letter in response to Tarallo <i>et al</i> 2022.","authors":"P Garfjeld Roberts","doi":"10.1308/rcsann.2022.0089","DOIUrl":"10.1308/rcsann.2022.0089","url":null,"abstract":"","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":" ","pages":"533"},"PeriodicalIF":17.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647412","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}