Journal of the American Chemical Society最新文献

{"title":"Tetraphenylethene-Based Molecular Cage with Coenzyme FAD: Conformationally Isomeric Complexation toward Photocatalysis-Assisted Photodynamic Therapy","authors":"Qingfang Li, Chaochao Yan, Peijuan Zhang, Pingxia Wang, Kaige Wang, Wanni Yang, Lin Cheng, Dongfeng Dang, Liping Cao","doi":"10.1021/jacs.4c09508","DOIUrl":"https://doi.org/10.1021/jacs.4c09508","url":null,"abstract":"Flavin adenine dinucleotide (FAD), serving as a light-absorbing coenzyme factor, can undergo conformationally isomeric complexation within different enzymes to form various enzyme–coenzyme complexes, which exhibit photocatalytic functions that play a crucial role in physiological processes. Constructing an artificial photofunctional system using FAD or its derivatives can not only develop biocompatible photocatalytic systems with excellent activities but also further enhance our understanding of the role of FAD in biological systems. Here, we demonstrate a supramolecular approach for constructing an artificial enzyme–coenzyme-type host–guest complex with photoinduced catalytic function in water. First, we have designed and synthesized a water-soluble tetraphenylethene (TPE)-based octacationic molecular cage (<b>1</b>) with a large and flexible cavity, which can adaptively encapsulate with two FAD molecules with “U-shaped” conformation (<i>u</i>FAD) to form a 1:2 host–guest complex (<b>1</b>⊃<i>u</i>FAD₂) in water. Second, based on the conformationally isomeric complexation of FAD within <b>1</b>, the <b>1</b>⊃<i>u</i>FAD₂ complex facilitates electron and energy transfers to molecular oxygen upon the white-light illumination, efficiently producing reactive oxygen species (ROS) such as superoxide radical (O₂^•–) and singlet oxygen (¹O₂). To our knowledge, the <b>1</b>⊃<i>u</i>FAD₂ complex acts as a photocatalyst to achieve the highest turnover frequency (TOF) of 35.6 min^–1 for the photocatalytic oxidation reaction of NADH via a photoinduced superoxide radical catalysis mechanism in an aqueous medium. At last, combining the cytotoxic effects of ROS and the disruption of the intracellular redox balance involving NADH, <b>1</b>⊃<i>u</i>FAD₂ as a supramolecular photosensitizer displays an excellent oxygen-independent photocatalysis-assisted photodynamic therapy in hypoxic tumors.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452389","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":"Selective Reduction of Nitroarenes via Noncontact Hydrogenation","authors":"Hua An, Yani Ding, Philippe Sautet, Geng Sun, Ning Yan","doi":"10.1021/jacs.4c06011","DOIUrl":"https://doi.org/10.1021/jacs.4c06011","url":null,"abstract":"In traditional hydrogenation, where H₂ and substrates with unsaturated bonds are activated on the same catalyst (contact mode), competitive hydrogenation of multiple reducible groups often occurs. We employ an unbiased H-cell for selective hydrogenation of the nitro group when multiple reducible groups are present. The setup spatially separates H₂ and nitroarenes into two chambers connected by a proton-exchange membrane, thus adding barriers for a Langmuir–Hinshelwood-type mechanism that is common in thermocatalytic hydrogenation. Through a unique proton/electron transfer pathway that is specific to nitro functional group reduction to hydroxylamine, side reactions like C═C, C═O, and C≡C bond hydrogenation are fully avoided. Using Pd/C for H₂ activation, and CNT for selective proton/electron transfer to −NO₂ groups while being inert to C≡C, C═C, and C═O hydrogenation, the system effectively eliminates the competitive hydrogenation, achieving 100% nitro-group reduction selectivity in the hydrogenation of various nitroarenes, in sharp contrast to negligible selectivity over the same catalysts in a batch reactor under contact mode. This device enables selectivity control in hydrogenation reactions, moving beyond the traditional focus on catalyst active site engineering.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452420","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":"Cascade CO2 Insertion in Carbanion Ionic Liquids Driven by Structure Rearrangement","authors":"Liqi Qiu, Bo Li, Jianzhi Hu, Arvind Ganesan, Subhamay Pramanik, Joshua T. Damron, Errui Li, De-en Jiang, Shannon M. Mahurin, Ilja Popovs, Carlos Alberto Steren, Juntian Fan, Zhenzhen Yang, Sheng Dai","doi":"10.1021/jacs.4c09933","DOIUrl":"https://doi.org/10.1021/jacs.4c09933","url":null,"abstract":"The CO₂ chemisorption in state-of-the-art sorbents based on oxide/hydroxide/amine moieties is driven by strong chemical bonding formation in the carbonate/bicarbonate/carbamate products, which in turn leads to high energy input in sorbent regeneration. In addition, the CO₂ uptake capacity was limited by the active sites’ utilization efficiency, with each active site incorporating one CO₂ molecule or less. In this work, a new concept and generation of sorbent was developed to achieve cascade insertion of multiple CO₂ molecules by leveraging structure rearrangement as the driving force, leading to in situ generation of extra CO₂-binding sites and significantly reduced energy input for CO₂ release. The designed ionic liquids (ILs) containing carbanions with conjugated and asymmetric structure, deprotonated (methylsulfonyl)acetonitrile ([MSA]) anion, allowed the cascade insertion of two CO₂ molecules via consecutive C–C and O–C bond formations. The proton transfer and structure rearrangement of the carboxylic acid intermediates played critical roles in stabilizing the first integrated CO₂ and generating extra electron-rich oxygen sites for the insertion of the second CO₂. The structure variation and reaction pathway were confirmed by operando spectroscopy, magnetic resonance spectroscopy (NMR), mass spectroscopy, and computational chemistry. The energy input in sorbent regeneration could be further reduced by harnessing the phase-changing behavior of the carbanion salts in ether solutions upon reacting with CO₂, avoiding the energy consumption in heating the solvent. The fundamental insights obtained herein provide a promising approach to greatly improve the CO₂ sorption performance via sophisticated molecular-scale structural engineering of the sorbents.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452030","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":"Microdroplet-Mediated Multiphase Cycling in a Cloud of Water Drives Chemoselective Electrolysis","authors":"Xuke Chen, Yu Xia, Yifan Yang, Yunpeng Xu, Xiuquan Jia, Richard N. Zare, Feng Wang","doi":"10.1021/jacs.4c11224","DOIUrl":"https://doi.org/10.1021/jacs.4c11224","url":null,"abstract":"Electrification of water in clouds leads to fascinating redox reactions on Earth. However, little is known about cloud electrochemistry, except for lightning, a natural hazard that is nearly impossible to harness. We report a controllable electrochemistry that can be enabled in microclouds by fast phase switching of water between the microdroplet, vapor, and bulk phase. Due to the size-dependent charge transfer between droplets during atomization, this process generates an alternating voltage arising from the self-electrification and discharging of microdroplets, vapor, and bulk phase by electron and ion transfer. We show that the microclouds with alternating voltage cause 1,2-dichloroethane (ClH₂C–CH₂Cl) to be converted to vinyl chloride (H₂C═CHCl) at ∼80% selectivity. These findings highlight the importance of controlled cloud electrochemistry in accelerating the removal of volatile organic compounds and treating contaminated water. We suggest that this work opens an avenue for harnessing cloud electrochemistry to solve challenging chemoselectivity problems in aqueous reactions of environmental and industrial importance.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451890","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":"Supramolecular Catalyzed Cascade Reduction of Azaarenes Interrogated via Data Science","authors":"Sean M. Treacy, Andrew L. Smith, Robert G. Bergman, Kenneth N. Raymond, F. Dean Toste","doi":"10.1021/jacs.4c11482","DOIUrl":"https://doi.org/10.1021/jacs.4c11482","url":null,"abstract":"Catalysis of multicomponent transformations requires controlled assembly of reactants within the active site. Supramolecular scaffolds possess synthetic microenvironments that enable precise modulation over noncovalent interactions (NCIs) engaged by reactive, encapsulated species. While molecular properties that describe the behavior of single guests in host cavities have been studied extensively, multicomponent transformations remain challenging to design and deploy. Here, simple univariate regression and threshold analyses are employed to model reactivity in a cascade reduction of azaarenes catalyzed by water-soluble metal organic cages. Yield and stereoselectivity models help deduce unknown mechanisms of reactivity by the multicomponent, host–guest complexes. Furthermore, a comprehensive model is established for NCIs driving stereoselectivity in the reported host–guest adducts.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452034","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":"Simultaneous Quantitation of Persulfides, Biothiols, and Hydrogen Sulfide through Sulfur Exchange Reaction with Trityl Spin Probes","authors":"Xiaoli Tan, Jiaxin Zhou, Luhua Yang, Qi Chang, Shao-Yong Li, Antal Rockenbauer, Yuguang Song, Yangping Liu","doi":"10.1021/jacs.4c10266","DOIUrl":"https://doi.org/10.1021/jacs.4c10266","url":null,"abstract":"Reactive sulfur species (RSS) including persulfides (RSSHs), biothiols, and hydrogen sulfide (H₂S) are key regulators in various physiological processes. To better understand the symbiotic relationship and interconversion of these RSS, it is highly desirable but challenging to develop analytical techniques that are capable of detecting and quantifying them. Herein, we report the rational design and synthesis of novel trityl-radical-based electron paramagnetic resonance (EPR) probes dubbed CT02-TNB and OX-TNB. CT02-TNB underwent fast sulfur exchange reactions with two reactive RSSHs (PS1 and PS2) which were released from their corresponding donors PSD1 and PSD2 to afford the specific conjugates. The resulting conjugates exhibit characteristic EPR spectra, thus enabling discriminative detection and quantitation of the two RSSHs. Moreover, CT02-TNB showed good response toward other RSS including glutathione (GSH), cysteine (Cys), H₂S, and sulfite as well. Importantly, based on the updated EPR spectral simulation program, simultaneous quantitation of multiple RSS (e.g., PS1/GSH/Cys or PS1/GSH/H₂S) by CT02-TNB was also achieved. Finally, the levels of released PS1 from PSD1 and endogenous GSH in isolated mouse livers were measured by the hydrophilic OX-TNB. This work represents the first study achieving discriminative and quantitative detection of different persulfides and other RSS by a spectroscopic method.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452438","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":"Development of Ribityllumazine Analogue as Mucosal-Associated Invariant T Cell Ligands","authors":"Ryosuke Takasaki, Emi Ito, Masamichi Nagae, Yuki Takahashi, Takuro Matsuoka, Wakana Yasue, Norihito Arichi, Hiroaki Ohno, Sho Yamasaki, Shinsuke Inuki","doi":"10.1021/jacs.4c12997","DOIUrl":"https://doi.org/10.1021/jacs.4c12997","url":null,"abstract":"Mucosal-associated invariant T (MAIT) cells are a subset of innate-like T cells abundant in human tissues that play a significant role in defense against bacterial and viral infections and in tissue repair. MAIT cells are activated by recognizing microbial-derived small-molecule ligands presented by the MHC class I related-1 protein. Although several MAIT cell modulators have been identified in the past decade, potent and chemically stable ligands remain limited. Herein, we carried out a structure–activity relationship study of ribityllumazine derivatives and found a chemically stable MAIT cell ligand with a pteridine core and a 2-oxopropyl group as the Lys-reactive group. The ligand showed high potency in a cocultivation assay using model cell lines of antigen-presenting cells and MAIT cells. The X-ray crystallographic analysis revealed the binding mode of the ligand to MR1 and the T cell receptor, indicating that it forms a covalent bond with MR1 via Schiff base formation. Furthermore, we found that the ligand stimulated proliferation of human MAIT cells in human peripheral blood mononuclear cells and showed an adjuvant effect in mice. Our developed ligand is one of the most potent among chemically stable MAIT cell ligands, contributing to accelerating therapeutic applications of MAIT cells.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451893","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":"Selective pH-Responsive Conjugation between a Pair of De Novo Discovered Peptides","authors":"Yuto Ohno, Alexander A. Vinogradov, Hiroaki Suga","doi":"10.1021/jacs.4c08520","DOIUrl":"https://doi.org/10.1021/jacs.4c08520","url":null,"abstract":"There is a demand for site-selective peptide/protein conjugation chemistry that is fully reversible in a stimulus-responsive manner. The contemporary methods for site-selective protein modification enable the preparation of homogeneous protein–small molecule conjugates, which are indispensable for drug delivery and chemical biology purposes, but such chemistries are usually irreversible. In contrast, the existing reversible protein labeling techniques are generally not site-selective. Here, we report an mRNA display-enabled <i>de novo</i> discovery of a pair of peptides which selectively react with each other to form a conjugate that is stable under neutral conditions (pH 7.5) but rapidly dissociates into the constituents at pH 10. A Cys thiol of peptide CP1 rapidly reacts (<i>k</i>₁ = 340 M^–1·s^–1) with the isothiocyanate moiety in partner ITC6 to furnish a stable dithiocarbamate (<i>t</i>_1/2 = 6 h at pH 7.5). We show that the pH-responsive nature of the reaction (conjugate’s <i>t</i>_1/2 = 5 min at pH 10) can be leveraged to utilize ITC6 (1) as a pull-down handle to selectively isolate CP1 from cell lysates and (2) as a temporary protecting group to protect CP1 from nonspecific Cys labeling reagents such as iodoacetamide. Altogether, the chemistry developed here complements the existing approaches and is applicable in a variety of chemical biology settings where selective reversible reactions are needed.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452166","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":"Short-Wave Infrared Upconverting Nanoparticles","authors":"Xiao Qi, Changhwan Lee, Benedikt Ursprung, Artiom Skripka, P. James Schuck, Emory M. Chan, Bruce E. Cohen","doi":"10.1021/jacs.4c11181","DOIUrl":"https://doi.org/10.1021/jacs.4c11181","url":null,"abstract":"Optical technologies enable real-time, noninvasive analysis of complex systems but are limited to discrete regions of the optical spectrum. While wavelengths in the short-wave infrared (SWIR) window (typically, 1700–3000 nm) should enable deep subsurface penetration and reduced photodamage, there are few luminescent probes that can be excited in this region. Here, we report the discovery of lanthanide-based upconverting nanoparticles (UCNPs) that efficiently convert 1740 or 1950 nm excitation to wavelengths compatible with conventional silicon detectors. Screening of Ln³⁺ ion combinations by differential rate equation modeling identifies Ho³⁺/Tm³⁺ or Tm³⁺ dopants with strong visible or NIR-I emission following SWIR excitation. Experimental upconverted photoluminescence excitation (U-PLE) spectra find that 10% Tm³⁺-doped NaYF₄ core/shell UCNPs have the strongest 800 nm emission from SWIR wavelengths, while UCNPs with an added 2% or 10% Ho³⁺ show the strongest red emission when excited at 1740 or 1950 nm. Mechanistic modeling shows that addition of a low percentage of Ho³⁺ to Tm³⁺-doped UCNPs shifts their emission from 800 to 652 nm by acting as a hub of efficient SWIR energy acceptance and redistribution up to visible emission manifolds. Parallel experimental and computational analysis shows rate equation models are able to predict compositions for specific wavelengths of both excitation and emission. These SWIR-responsive probes open a new IR bioimaging window, and are responsive at wavelengths important for vision technologies.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452423","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":"Skeletal Editing of Mechanically Interlocked Molecules: Nitrogen Atom Deletion from Crown Ether-Dibenzylammonium Rotaxanes","authors":"Maxime Gauthier, Jessica B. M. Whittingham, Avantika Hasija, Daniel J. Tetlow, David A. Leigh","doi":"10.1021/jacs.4c09066","DOIUrl":"https://doi.org/10.1021/jacs.4c09066","url":null,"abstract":"Removing the nitrogen atom from secondary amines while simultaneously linking the remaining fragments is a powerful form of late-stage skeletal editing. Here, we report its use for the deletion of the nitrogen atom of the dibenzylammonium template used to assemble crown ether rotaxanes. The reaction uses an anomeric amide that activates secondary amines to generate a carbon–carbon bond that replaces the amine nitrogen. Despite the potential for dethreading of the intermediate diradical pair, the nitrogen atom was successfully deleted from a series of rotaxane axles as long as the macrocycle could access coconformations that did not inhibit the reaction of the amine group. The skeletally edited interlocked molecules were obtained directly from the parent crown ether-dibenzylammonium rotaxanes in modest yields (23–36%) and characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography. One skeletally edited rotaxane shows a network of weak CH···O hydrogen bonds between the crown ether and benzylic methylene groups of the axle in the solid state, in place of the crown ether-ammonium binding motif used to assemble the parent, unedited, rotaxane.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142451889","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}