JACS Au最新文献

{"title":"Is Cocaine Protonated When it Binds to the Dopamine Transporter?","authors":"Marie L. Gram,&nbsp;Julia M. Warren,&nbsp;Emilie L. Madsen,&nbsp;Jeppe C. Nielsen,&nbsp;Claus J. Loland* and Mikael Bols*,&nbsp;","doi":"10.1021/jacsau.4c0095210.1021/jacsau.4c00952","DOIUrl":"https://doi.org/10.1021/jacsau.4c00952https://doi.org/10.1021/jacsau.4c00952","url":null,"abstract":"<p >There has been much controversy about whether the well-known alkaloid and tertiary amine base cocaine (p<i>K</i>_a = 8.5) binds to the human dopamine transporter (DAT) in its protonated form. Most potent DAT inhibitors are also strong amines─yet there are some noteworthy examples where neutral cocaine analogues have high affinity, while the quaternary ammonium analog of cocaine, cocaine methiodide, is a comparatively poor inhibitor. In this paper, we show that a fluorescent cocaine analog, with a lower p<i>K</i>_a than cocaine, becomes protonated in the DAT binding site and conclude that similar behavior must be expected from cocaine. By determining the p<i>K</i>_a of the aspartate residue in DAT believed to interact with the amine of cocaine, we are able to explain the apparently contradictory structure–activity data of cocaine analogues.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1157–1172 1157–1172"},"PeriodicalIF":8.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00952","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring the Selective Oxidation of Hydroxyl-Containing Compounds via Precisely Tuning the Hydrogen-Bond Strength of Catalyst H-Bond Acceptors.","authors":"Xiao Feng, Piaoping Yang, Yinwei Wang, Jieqi Cao, Jin Gao, Song Shi, Dionisios G Vlachos","doi":"10.1021/jacsau.4c01262","DOIUrl":"10.1021/jacsau.4c01262","url":null,"abstract":"<p><p>The unique performance of the enzyme is mainly achieved via weak interactions between the \"outer coordination sphere\" and the substrate. Inspired by this process, we developed 3D encapsulated-structure catalysts with hydrogen-bond engineering on the shell, which mimics the \"outer coordination sphere\" of an enzyme. Various hydrogen bond acceptors (C=O, S=O, and N-O groups) are imparted in the shell. Concentration-dependent ¹H NMR, inverse-phase gas Chromatography (IGC) measurements, and DFT calculations underscore that the hydrogen bond strength between the acceptor groups and alcohol follows the order of C=O < S=O < N-O. The hydroxyl compound oxidation rate vs the hydrogen bond strength follows a volcano behavior, reminiscent of Sabatier's principle. The performance variation among catalysts is attributed to the adsorption strength of the substrate. The proposed bioinspired design principle expands the scope of encapsulated catalysts, enabling fine regulation of catalytic activity through precise microenvironment control via weak interactions with substrates.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1359-1366"},"PeriodicalIF":8.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Cocaine Protonated When it Binds to the Dopamine Transporter?","authors":"Marie L Gram, Julia M Warren, Emilie L Madsen, Jeppe C Nielsen, Claus J Loland, Mikael Bols","doi":"10.1021/jacsau.4c00952","DOIUrl":"10.1021/jacsau.4c00952","url":null,"abstract":"<p><p>There has been much controversy about whether the well-known alkaloid and tertiary amine base cocaine (p<i>K</i> _a = 8.5) binds to the human dopamine transporter (DAT) in its protonated form. Most potent DAT inhibitors are also strong amines-yet there are some noteworthy examples where neutral cocaine analogues have high affinity, while the quaternary ammonium analog of cocaine, cocaine methiodide, is a comparatively poor inhibitor. In this paper, we show that a fluorescent cocaine analog, with a lower p<i>K</i> _a than cocaine, becomes protonated in the DAT binding site and conclude that similar behavior must be expected from cocaine. By determining the p<i>K</i> _a of the aspartate residue in DAT believed to interact with the amine of cocaine, we are able to explain the apparently contradictory structure-activity data of cocaine analogues.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1157-1172"},"PeriodicalIF":8.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring the Selective Oxidation of Hydroxyl-Containing Compounds via Precisely Tuning the Hydrogen-Bond Strength of Catalyst H-Bond Acceptors","authors":"Xiao Feng,&nbsp;Piaoping Yang,&nbsp;Yinwei Wang,&nbsp;Jieqi Cao,&nbsp;Jin Gao*,&nbsp;Song Shi* and Dionisios G. Vlachos*,&nbsp;","doi":"10.1021/jacsau.4c0126210.1021/jacsau.4c01262","DOIUrl":"https://doi.org/10.1021/jacsau.4c01262https://doi.org/10.1021/jacsau.4c01262","url":null,"abstract":"<p >The unique performance of the enzyme is mainly achieved via weak interactions between the “outer coordination sphere” and the substrate. Inspired by this process, we developed 3D encapsulated-structure catalysts with hydrogen-bond engineering on the shell, which mimics the “outer coordination sphere” of an enzyme. Various hydrogen bond acceptors (C═O, S═O, and N–O groups) are imparted in the shell. Concentration-dependent ¹H NMR, inverse-phase gas Chromatography (IGC) measurements, and DFT calculations underscore that the hydrogen bond strength between the acceptor groups and alcohol follows the order of C═O &lt; S═O &lt; N–O. The hydroxyl compound oxidation rate vs the hydrogen bond strength follows a volcano behavior, reminiscent of Sabatier’s principle. The performance variation among catalysts is attributed to the adsorption strength of the substrate. The proposed bioinspired design principle expands the scope of encapsulated catalysts, enabling fine regulation of catalytic activity through precise microenvironment control via weak interactions with substrates.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1359–1366 1359–1366"},"PeriodicalIF":8.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Workflow Enabling the Automated Synthesis, Chain-End Degradation, and Rapid Mass Spectrometry Analysis for Molecular Information Storage in Sequence-Defined Oligourethanes","authors":"Julia R. Shuluk,&nbsp;Christopher D. Wight,&nbsp;James R. Howard,&nbsp;Mary E. King,&nbsp;Sarah R. Moor,&nbsp;Rachel J. DeHoog,&nbsp;Samuel D. Dahlhauser,&nbsp;Livia S. Eberlin* and Eric V. Anslyn*,&nbsp;","doi":"10.1021/jacsau.4c0107010.1021/jacsau.4c01070","DOIUrl":"https://doi.org/10.1021/jacsau.4c01070https://doi.org/10.1021/jacsau.4c01070","url":null,"abstract":"<p >The field of molecular information storage has recently expanded to include abiotic sequence-defined polymers. While robust methods have been developed, there is a current bottleneck in the throughput of this work as information density is increased. Herein, we introduce an automated workflow in which a commercial peptide synthesizer composed of a single XYZ liquid-handling robot was adapted to both synthesize and sequence sequence-defined oligourethanes. Our sequencing method was improved to cut down the number of samples required for each oligomer from 13 to one. Additionally, we introduce the use of desorption electrospray ionization mass spectrometry as our analysis method for sequencing, which allowed for simplified and increased speed of data acquisition. Finally, we created a Python script that is able to reconstruct the sequence information from the MS data in an automated fashion. We demonstrate this new workflow by encoding and decoding a quote from the late Maya Angelou: “When you learn, teach, when you get, give”.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1232–1242 1232–1242"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dicationic 1-Germa and 1-Stannavinylidenes: Synthesis, Structure, and Reactivity","authors":"Yuankai Li,&nbsp;Huan Mu,&nbsp;Zhuchunguang Liu,&nbsp;Zexin Qi,&nbsp;Jiliang Zhou and Zhaowen Dong*,&nbsp;","doi":"10.1021/jacsau.4c0113910.1021/jacsau.4c01139","DOIUrl":"https://doi.org/10.1021/jacsau.4c01139https://doi.org/10.1021/jacsau.4c01139","url":null,"abstract":"<p >The synthesis of heteronuclear vinylidene analogues containing heavier group 14 elements (R₂C═E:, E = Si, Ge, Sn) has been a challenging task due to their inherent instability. In this study, we report the synthesis of dicationic 1-germavinylidene (<b>3Ge</b>) and 1-stannavinylidene (<b>3Sn</b>) by using sym-bis(2-pyridyl)-tetraphenylcarbodiphosphorane (CDPPy₂) as a donor ligand. Both <b>3Ge</b> and <b>3Sn</b> have been characterized by single-crystal X-ray diffraction analysis, NMR spectroscopy, and high-resolution mass spectrometry. The structural analysis, supported by the results of theoretical calculations, confirms that <b>3Ge</b> and <b>3Sn</b> feature a polarized C═E double bond and a lone pair of electrons located at the E atom (E = Ge and Sn). The reactions of <b>3Ge</b> with IDippMCl (M = Cu, Ag, Au) give the M–Cl bond addition products. Mechanistic studies on the activation of the Au–Cl bond by <b>3Ge</b> demonstrate its ambiphilicity. This work represents an example of the utilization of a carbone ligand as both an σ and π donor for the synthesis of heavier heteronuclear vinylidene analogues.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1289–1298 1289–1298"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a Distinctive Reagent for Divergent Arene Trifluoromethylsulfinylation","authors":"Liuqing Yang,&nbsp;Lu Yu,&nbsp;Lulu Liu,&nbsp;Luyao Wang,&nbsp;Yu Zhong,&nbsp;Fangcan Liang,&nbsp;Chenfengtao Zheng,&nbsp;Ji-Quan Liu,&nbsp;Xiao-Song Xue* and Dianhu Zhu*,&nbsp;","doi":"10.1021/jacsau.5c0007210.1021/jacsau.5c00072","DOIUrl":"https://doi.org/10.1021/jacsau.5c00072https://doi.org/10.1021/jacsau.5c00072","url":null,"abstract":"<p >Simple and direct arene trifluoromethylsulfinylation is highly desirable in drug design but remains a major challenge. Herein, we report a modular, mild, innate C–H trifluoromethylsulfinylation of a wide variety of arenes via a distinctive trifluoromethylsulfinylating reagent <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate following divergent efficient pathways. This trifluoromethylsulfinylation can be conducted in a redox-neutral manner at room temperature with light-, metal-, and photocatalyst-free mild conditions. Mechanistic studies and density functional theory (DFT) calculations revealed that the success of this approach hinges upon the design of an activated trifluoromethanesulfite ester that proceeds via homolytic cleavage with a very low bond dissociation energy to generate a dummy aminoxyl radical (PINO) and active CF₃S(O) radical, which could accidentally be transformed into a trifluoromethanesulfonic anhydride, CF₃S(O)OS(O)CF₃, for the transfer of the S(O)CF₃ group into an exemplary set of strong EDG-substituted arenes. DFT computation corroborates that this novel reagent can be activated by TfOH via heterolytic cleavage to produce highly active CF₃S(O)OTf, which is responsible for electrophilic trifluoromethylsulfinylation of the challenging weak EDG-substituted arene substrates through an electrophilic addition–elimination mechanism. Such C–H functionalization using <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate affords an innovative strategy and marked improvement over functionalization with previously developed reagents. Notably, simple and mild conditions, broad reactivities, good functional group compatibility, divergent reaction modes (homolysis and heterolysis), as well as late-stage trifluoromethylsulfinylation (LST) of complex biologically active molecules in these reactions underline the great potential of <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate for the preparation of functionalized drug-like molecules.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1448–1459 1448–1459"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Workflow Enabling the Automated Synthesis, Chain-End Degradation, and Rapid Mass Spectrometry Analysis for Molecular Information Storage in Sequence-Defined Oligourethanes.","authors":"Julia R Shuluk, Christopher D Wight, James R Howard, Mary E King, Sarah R Moor, Rachel J DeHoog, Samuel D Dahlhauser, Livia S Eberlin, Eric V Anslyn","doi":"10.1021/jacsau.4c01070","DOIUrl":"10.1021/jacsau.4c01070","url":null,"abstract":"<p><p>The field of molecular information storage has recently expanded to include abiotic sequence-defined polymers. While robust methods have been developed, there is a current bottleneck in the throughput of this work as information density is increased. Herein, we introduce an automated workflow in which a commercial peptide synthesizer composed of a single XYZ liquid-handling robot was adapted to both synthesize and sequence sequence-defined oligourethanes. Our sequencing method was improved to cut down the number of samples required for each oligomer from 13 to one. Additionally, we introduce the use of desorption electrospray ionization mass spectrometry as our analysis method for sequencing, which allowed for simplified and increased speed of data acquisition. Finally, we created a Python script that is able to reconstruct the sequence information from the MS data in an automated fashion. We demonstrate this new workflow by encoding and decoding a quote from the late Maya Angelou: \"When you learn, teach, when you get, give\".</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1232-1242"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11937967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dicationic 1-Germa and 1-Stannavinylidenes: Synthesis, Structure, and Reactivity.","authors":"Yuankai Li, Huan Mu, Zhuchunguang Liu, Zexin Qi, Jiliang Zhou, Zhaowen Dong","doi":"10.1021/jacsau.4c01139","DOIUrl":"10.1021/jacsau.4c01139","url":null,"abstract":"<p><p>The synthesis of heteronuclear vinylidene analogues containing heavier group 14 elements (R₂C=E:, E = Si, Ge, Sn) has been a challenging task due to their inherent instability. In this study, we report the synthesis of dicationic 1-germavinylidene (<b>3Ge</b>) and 1-stannavinylidene (<b>3Sn</b>) by using sym-bis(2-pyridyl)-tetraphenylcarbodiphosphorane (CDPPy₂) as a donor ligand. Both <b>3Ge</b> and <b>3Sn</b> have been characterized by single-crystal X-ray diffraction analysis, NMR spectroscopy, and high-resolution mass spectrometry. The structural analysis, supported by the results of theoretical calculations, confirms that <b>3Ge</b> and <b>3Sn</b> feature a polarized C=E double bond and a lone pair of electrons located at the E atom (E = Ge and Sn). The reactions of <b>3Ge</b> with IDippMCl (M = Cu, Ag, Au) give the M-Cl bond addition products. Mechanistic studies on the activation of the Au-Cl bond by <b>3Ge</b> demonstrate its ambiphilicity. This work represents an example of the utilization of a carbone ligand as both an σ and π donor for the synthesis of heavier heteronuclear vinylidene analogues.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1289-1298"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a Distinctive Reagent for Divergent Arene Trifluoromethylsulfinylation.","authors":"Liuqing Yang, Lu Yu, Lulu Liu, Luyao Wang, Yu Zhong, Fangcan Liang, Chenfengtao Zheng, Ji-Quan Liu, Xiao-Song Xue, Dianhu Zhu","doi":"10.1021/jacsau.5c00072","DOIUrl":"10.1021/jacsau.5c00072","url":null,"abstract":"<p><p>Simple and direct arene trifluoromethylsulfinylation is highly desirable in drug design but remains a major challenge. Herein, we report a modular, mild, innate C-H trifluoromethylsulfinylation of a wide variety of arenes via a distinctive trifluoromethylsulfinylating reagent <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate following divergent efficient pathways. This trifluoromethylsulfinylation can be conducted in a redox-neutral manner at room temperature with light-, metal-, and photocatalyst-free mild conditions. Mechanistic studies and density functional theory (DFT) calculations revealed that the success of this approach hinges upon the design of an activated trifluoromethanesulfite ester that proceeds via homolytic cleavage with a very low bond dissociation energy to generate a dummy aminoxyl radical (PINO) and active CF₃S(O) radical, which could accidentally be transformed into a trifluoromethanesulfonic anhydride, CF₃S(O)OS(O)CF₃, for the transfer of the S(O)CF₃ group into an exemplary set of strong EDG-substituted arenes. DFT computation corroborates that this novel reagent can be activated by TfOH via heterolytic cleavage to produce highly active CF₃S(O)OTf, which is responsible for electrophilic trifluoromethylsulfinylation of the challenging weak EDG-substituted arene substrates through an electrophilic addition-elimination mechanism. Such C-H functionalization using <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate affords an innovative strategy and marked improvement over functionalization with previously developed reagents. Notably, simple and mild conditions, broad reactivities, good functional group compatibility, divergent reaction modes (homolysis and heterolysis), as well as late-stage trifluoromethylsulfinylation (LST) of complex biologically active molecules in these reactions underline the great potential of <i>N</i>-hydroxyphthalimide-<i>O</i>-trifluoromethanesulfinate for the preparation of functionalized drug-like molecules.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 3","pages":"1448-1459"},"PeriodicalIF":8.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}