JACS Au最新文献

{"title":"How the Larger Methionine-Rich Domain of CueO from <i>Hafnia alvei</i> Enhances Cuprous Oxidation.","authors":"Umberto Contaldo, Paolo Santucci, Alexandra Vergnes, Philippe Leone, Jérôme Becam, Frédéric Biaso, Marianne Ilbert, Benjamin Ezraty, Elisabeth Lojou, Ievgen Mazurenko","doi":"10.1021/jacsau.5c00076","DOIUrl":"https://doi.org/10.1021/jacsau.5c00076","url":null,"abstract":"<p><p>CueOs, members of the multicopper oxidase family, play a crucial role in bacterial copper detoxification. These enzymes feature a unique methionine-rich (Met-rich) domain, which is essential for the oxidation of Cu⁺ to Cu²⁺. Recent studies using CueO from <i><i>Escherichia coli</i></i> (<i>Ec</i>CueO) suggest that the Met-rich domain facilitates Cu⁺ recruitment from highly chelated species. To further explore this hypothesis, we produced and characterized a novel CueO from the bacterium <i>Hafnia alvei</i> (<i>Ha</i>CueO). <i>Ha</i>CueO possesses a significantly larger Met-rich domain than <i>Ec</i>CueO, providing new insights into the role of this domain in cuprous oxidase activity. We first showed that <i>Ha</i>CueO was as efficient in copper detoxification as <i>Ec</i>CueO in vivo. The structures of both wild-type <i>Ha</i>CueO and a variant lacking the Met-rich domain were resolved by X-ray crystallography and simulated by molecular dynamics, offering a detailed structural basis for understanding their functions. Cuprous oxidase activity was then quantified either from free electrogenerated Cu⁺ with CueO immobilized on an electrode or from different Cu⁺-complexes with CueO in solution. These methods enabled the fine-tuning of Cu⁺ chelation strength. Consistent with findings for <i>Ec</i>CueO, it was confirmed that the Met-rich domain of <i>Ha</i>CueO is dispensable for Cu⁺ oxidation when weakly chelated Cu⁺ is used. However, its role becomes crucial as chelation strength increases. Comparative analyses of cuprous oxidase activity between <i>Ha</i>CueO and <i>Ec</i>CueO revealed that <i>Ha</i>CueO outperforms <i>Ec</i>CueO, demonstrating superior efficiency in oxidizing Cu⁺ from chelated forms. This enhanced activity correlates with the higher methionine content in <i>Ha</i>CueO, which appears to play a pivotal role in facilitating Cu⁺ oxidation under conditions of stronger chelation.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1833-1844"},"PeriodicalIF":8.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995625","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":"Manipulating the Interfacial Hydrophobic Microenvironment via Electrolyte Engineering Promotes Electrocatalytic Fatty Alcohol Oxidation Coupled with Hydrogen Production","authors":"Ruiqi Du,&nbsp;Zemao Chen,&nbsp;Shiyan Wang,&nbsp;Shumao Zeng,&nbsp;Rui Jia,&nbsp;Kaizheng Zhang,&nbsp;Diannan Lu,&nbsp;Haihui Wang* and Yi Cheng*,&nbsp;","doi":"10.1021/jacsau.5c0021510.1021/jacsau.5c00215","DOIUrl":"https://doi.org/10.1021/jacsau.5c00215https://doi.org/10.1021/jacsau.5c00215","url":null,"abstract":"<p >The selective oxidation of fatty alcohols to fatty acids represents a pivotal transformation in organic synthesis. Traditional methods often require harsh conditions and environmentally harmful oxidants or solvents. Electrocatalytic oxidation emerges as a promising green alternative, enabling mild oxidation in aqueous media and concurrent energy-efficient hydrogen production at the cathode. However, the poor solubility of fatty alcohols in water poses a significant challenge, reducing the reactant availability at the electrode surface, thereby hindering mass transfer and overall reaction rates. Herein, we develop an electrolyte engineering strategy that incorporates cetyltrimethylammonium hydroxide (CTAOH) as an additive. This strategy significantly enhances the oxidation current density of fatty alcohols as well as the production rate of fatty acids on a gold electrocatalyst. Through a mechanistic investigation combining experimental evidence from a quartz crystal microbalance (QCM) and in situ attenuated total reflectance surface-enhanced infrared spectroscopy (ATR-SEIRAS) with molecular dynamics (MD) simulations, we confirm that the preferential adsorption of CTAOH creates a hydrophobic interfacial microenvironment at the anode, promoting the enrichment of reactant at the electrode–electrolyte interface. This work highlights the significance of interfacial hydrophobicity modulation in boosting aqueous-phase electrocatalytic oxidation, paving the way for more efficient electrocatalytic transformations involving water-insoluble reactants.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1974–1982 1974–1982"},"PeriodicalIF":8.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878188","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":"Disentangling the Contribution of Surface and Bulk Ti3+ Defects to the Band Gap States of Rutile TiO2(011)","authors":"Yajie Gao,&nbsp;Kaiping Wang,&nbsp;Tianjun Wang,&nbsp;Shucai Xia,&nbsp;Qunqing Hao,&nbsp;Zhiqiang Wang,&nbsp;Bo Wen*,&nbsp;Zefeng Ren,&nbsp;Xueming Yang,&nbsp;Annabella Selloni* and Chuanyao Zhou*,&nbsp;","doi":"10.1021/jacsau.5c0007510.1021/jacsau.5c00075","DOIUrl":"https://doi.org/10.1021/jacsau.5c00075https://doi.org/10.1021/jacsau.5c00075","url":null,"abstract":"<p >Band gap states (BGS) induced by Ti³⁺ defects play a pivotal role in the physical and chemical properties of TiO₂. However, there is no consensus on the relative contributions of surface and bulk Ti³⁺ defects to the BGS measured by ultraviolet photoelectron spectroscopy (UPS). This is mainly due to the lack of vertical spatial resolution of UPS and limitations in the preparation and quantitative characterization of bulk Ti³⁺ defects. In this study, we create surface and bulk Ti³⁺ defects in a controllable way by introducing surface and bulk hydroxyls into rutile TiO₂(011)-(2 × 1) via atomic deuterium exposure. Utilizing UPS combined with density functional theory (DFT) calculations, we successfully disentangled the contributions of surface and bulk Ti³⁺ defects to the BGS. The UPS data indicate that surface and bulk Ti³⁺ defects give rise to BGS at binding energies of approximately 0.85 and 1.57 eV, respectively. DFT calculations reveal that the separation of surface and bulk BGS originates from the distinct atomic environments of surface and bulk Ti³⁺ ions that induce characteristic 3d orbital splittings. Our finding that the surface and bulk Ti³⁺(OH) states are separated in energy could provide a fingerprint for the in situ monitoring of metal–support interactions and hydrogenation reactions in heterogeneous catalysis.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1822–1832 1822–1832"},"PeriodicalIF":8.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878189","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":"How the Larger Methionine-Rich Domain of CueO from Hafnia alvei Enhances Cuprous Oxidation","authors":"Umberto Contaldo*,&nbsp;Paolo Santucci,&nbsp;Alexandra Vergnes,&nbsp;Philippe Leone,&nbsp;Jérôme Becam,&nbsp;Frédéric Biaso,&nbsp;Marianne Ilbert,&nbsp;Benjamin Ezraty,&nbsp;Elisabeth Lojou* and Ievgen Mazurenko*,&nbsp;","doi":"10.1021/jacsau.5c0007610.1021/jacsau.5c00076","DOIUrl":"https://doi.org/10.1021/jacsau.5c00076https://doi.org/10.1021/jacsau.5c00076","url":null,"abstract":"<p >CueOs, members of the multicopper oxidase family, play a crucial role in bacterial copper detoxification. These enzymes feature a unique methionine-rich (Met-rich) domain, which is essential for the oxidation of Cu⁺ to Cu²⁺. Recent studies using CueO from <i><i>Escherichia coli</i></i> (<i>Ec</i>CueO) suggest that the Met-rich domain facilitates Cu⁺ recruitment from highly chelated species. To further explore this hypothesis, we produced and characterized a novel CueO from the bacterium <i>Hafnia alvei</i> (<i>Ha</i>CueO). <i>Ha</i>CueO possesses a significantly larger Met-rich domain than <i>Ec</i>CueO, providing new insights into the role of this domain in cuprous oxidase activity. We first showed that <i>Ha</i>CueO was as efficient in copper detoxification as <i>Ec</i>CueO in vivo. The structures of both wild-type <i>Ha</i>CueO and a variant lacking the Met-rich domain were resolved by X-ray crystallography and simulated by molecular dynamics, offering a detailed structural basis for understanding their functions. Cuprous oxidase activity was then quantified either from free electrogenerated Cu⁺ with CueO immobilized on an electrode or from different Cu⁺-complexes with CueO in solution. These methods enabled the fine-tuning of Cu⁺ chelation strength. Consistent with findings for <i>Ec</i>CueO, it was confirmed that the Met-rich domain of <i>Ha</i>CueO is dispensable for Cu⁺ oxidation when weakly chelated Cu⁺ is used. However, its role becomes crucial as chelation strength increases. Comparative analyses of cuprous oxidase activity between <i>Ha</i>CueO and <i>Ec</i>CueO revealed that <i>Ha</i>CueO outperforms <i>Ec</i>CueO, demonstrating superior efficiency in oxidizing Cu⁺ from chelated forms. This enhanced activity correlates with the higher methionine content in <i>Ha</i>CueO, which appears to play a pivotal role in facilitating Cu⁺ oxidation under conditions of stronger chelation.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1833–1844 1833–1844"},"PeriodicalIF":8.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878161","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":"Electrochemical Observation and pH Dependence of All Three Expected Redox Couples in an Extremophilic Bifurcating Electron Transfer Flavoprotein with Fused Subunits.","authors":"Debarati Das, Wassim El Housseini, Monica Brachi, Shelley D Minteer, Anne-Frances Miller","doi":"10.1021/jacsau.4c01219","DOIUrl":"https://doi.org/10.1021/jacsau.4c01219","url":null,"abstract":"<p><p>Bifurcating enzymes employ energy from a favorable electron transfer to drive unfavorable transfer of a second electron, thereby generating a more reactive product. They are therefore highly desirable in catalytic systems, for example, to drive challenging reactions such as nitrogen fixation. While most bifurcating enzymes contain air-sensitive metal centers, bifurcating electron transfer flavoproteins (bETFs) employ flavins. However, they have not been successfully deployed on electrodes. Herein, we demonstrate immobilization and expected thermodynamic reactivity of a bETF from a hyperthermophilic archaeon, <i>Sulfolobus acidocaldarius</i> (<i>Sa</i>ETF). <i>Sa</i>ETF differs from previously biochemically characterized bETFs in being a single protein, representing a concatenation of the two subunits of known ETFs. However, <i>Sa</i>ETF retains the chemical properties of heterodimeric bETFs, including possession of two FADs: one that undergoes sequential 1-electron (1e) reductions at high E° and forms an anionic semiquinone, and another that is amenable to lower-E° 2e reduction, including by NADH. We found homologous monomeric ETF genes in archaeal and bacterial genomes, accompanied by genes that also commonly flank heterodimeric ETFs, and <i>Sa</i>ETF's sequence conservation is 50% higher with bETFs than with canonical ETFs. Thus, <i>Sa</i>ETF is best described as a bETF. Our direct electrochemical trials capture reversible redox couples for all three thermodynamically expected redox events. We document electrochemical activity over a range of pH values and reveal a conformational change coupled to proton acquisition that affects the electrochemical activity of the higher-E° FAD. Thus, this well-behaved monomeric bETF opens the door to bioinspired bifurcating devices or bifurcation on a chip.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1689-1706"},"PeriodicalIF":8.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039704","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":"Electrochemical Observation and pH Dependence of All Three Expected Redox Couples in an Extremophilic Bifurcating Electron Transfer Flavoprotein with Fused Subunits","authors":"Debarati Das,&nbsp;Wassim El Housseini,&nbsp;Monica Brachi,&nbsp;Shelley D. Minteer* and Anne-Frances Miller*,&nbsp;","doi":"10.1021/jacsau.4c0121910.1021/jacsau.4c01219","DOIUrl":"https://doi.org/10.1021/jacsau.4c01219https://doi.org/10.1021/jacsau.4c01219","url":null,"abstract":"<p >Bifurcating enzymes employ energy from a favorable electron transfer to drive unfavorable transfer of a second electron, thereby generating a more reactive product. They are therefore highly desirable in catalytic systems, for example, to drive challenging reactions such as nitrogen fixation. While most bifurcating enzymes contain air-sensitive metal centers, bifurcating electron transfer flavoproteins (bETFs) employ flavins. However, they have not been successfully deployed on electrodes. Herein, we demonstrate immobilization and expected thermodynamic reactivity of a bETF from a hyperthermophilic archaeon, <i>Sulfolobus acidocaldarius</i> (<i>Sa</i>ETF). <i>Sa</i>ETF differs from previously biochemically characterized bETFs in being a single protein, representing a concatenation of the two subunits of known ETFs. However, <i>Sa</i>ETF retains the chemical properties of heterodimeric bETFs, including possession of two FADs: one that undergoes sequential 1-electron (1e) reductions at high E° and forms an anionic semiquinone, and another that is amenable to lower-E° 2e reduction, including by NADH. We found homologous monomeric ETF genes in archaeal and bacterial genomes, accompanied by genes that also commonly flank heterodimeric ETFs, and <i>Sa</i>ETF’s sequence conservation is 50% higher with bETFs than with canonical ETFs. Thus, <i>Sa</i>ETF is best described as a bETF. Our direct electrochemical trials capture reversible redox couples for all three thermodynamically expected redox events. We document electrochemical activity over a range of pH values and reveal a conformational change coupled to proton acquisition that affects the electrochemical activity of the higher-E° FAD. Thus, this well-behaved monomeric bETF opens the door to bioinspired bifurcating devices or bifurcation on a chip.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1689–1706 1689–1706"},"PeriodicalIF":8.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c01219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878282","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":"Amino Acid Electrosynthesis with Oxygen Vacancy-Mediated CeO2 Nanocrystals: Facet Effect and Catalytic Mechanism","authors":"Jiang Shao,&nbsp;Jun-Hao Wang,&nbsp;Yi-Fei Zhang,&nbsp;Sheng-Zhi Xue,&nbsp;Hao Dong,&nbsp;Hai-Chao Liu,&nbsp;Chen Li* and Ya-Wen Zhang*,&nbsp;","doi":"10.1021/jacsau.5c0025210.1021/jacsau.5c00252","DOIUrl":"https://doi.org/10.1021/jacsau.5c00252https://doi.org/10.1021/jacsau.5c00252","url":null,"abstract":"<p >Amino acids are widely used in food, pharmaceuticals, and agrochemicals, presenting significant societal demand, and the artificial synthesis of amino acids is an important yet challenging task. Through electrocatalytic C–N coupling, the synthesis of amino acids from biomass α-keto acids and waste nitrate under mild aqueous conditions has become a green and alternative strategy. Rare-earth-based materials, due to their unique 4f orbitals and tunable crystal facets, often serve as potential resource-rich catalysts. However, their structure–performance relationship in C–N coupling for amino acids synthesis remains unclear. Therefore, eight rare-earth-based catalysts were screened in this work and CeO₂ was chosen as an appropriate model catalyst for the mechanism investigation on the electrosynthesis of alanine. Four CeO₂ nanomaterials with distinct morphologies and crystal facets were synthesized, among which CeO₂ nanorods (CeO₂-NRs) exposing the (110) facet exhibited the highest oxygen vacancy (O_v) concentration and optimal electrosynthetic performance for alanine. A series of control experiments, electrochemical characterizations, <i>in situ</i> electrochemical attenuated total reflection Fourier transform infrared spectroscopy (<i>in situ</i> ATR-FTIR), online electrochemical differential mass spectrometry (DEMS), quasi <i>in situ</i> electron paramagnetic resonance (quasi <i>in situ</i> EPR) experiments, combined with density functional theory (DFT) calculations indicated that the synthesis pathway for alanine involved the reduction of NO₃^– to produce ^*NH₂OH <i>in situ</i>, which nucleophilically attacked the carbonyl group of pyruvate to form the key intermediate species, oxime, then underwent further amination to generate alanine. The key step responsible for the performance difference of four CeO₂ nanocrystals lay in the reduction amination of pyruvate oxime (PO), confirming the (110) facet with more O_v exposure facilitated the cleavage of the N–O bond in pyruvate oxime (^*OOC(H₃C)C═N–OH→^*OOC(H₃C)C═N), while also lowering the energy consumption for the hydrogenation of the C═N bond (^*OOC(H₃C)C═NH→^*OOC(H₃C)CNH₂). This innovative strategy not only provides a new route for the valorization of biomass and waste nitrate but also offers valuable guidance for the design of more efficient rare-earth-based catalysts in this field.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"2015–2026 2015–2026"},"PeriodicalIF":8.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878277","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":"Amino Acid Electrosynthesis with Oxygen Vacancy-Mediated CeO₂ Nanocrystals: Facet Effect and Catalytic Mechanism.","authors":"Jiang Shao, Jun-Hao Wang, Yi-Fei Zhang, Sheng-Zhi Xue, Hao Dong, Hai-Chao Liu, Chen Li, Ya-Wen Zhang","doi":"10.1021/jacsau.5c00252","DOIUrl":"https://doi.org/10.1021/jacsau.5c00252","url":null,"abstract":"<p><p>Amino acids are widely used in food, pharmaceuticals, and agrochemicals, presenting significant societal demand, and the artificial synthesis of amino acids is an important yet challenging task. Through electrocatalytic C-N coupling, the synthesis of amino acids from biomass α-keto acids and waste nitrate under mild aqueous conditions has become a green and alternative strategy. Rare-earth-based materials, due to their unique 4f orbitals and tunable crystal facets, often serve as potential resource-rich catalysts. However, their structure-performance relationship in C-N coupling for amino acids synthesis remains unclear. Therefore, eight rare-earth-based catalysts were screened in this work and CeO₂ was chosen as an appropriate model catalyst for the mechanism investigation on the electrosynthesis of alanine. Four CeO₂ nanomaterials with distinct morphologies and crystal facets were synthesized, among which CeO₂ nanorods (CeO₂-NRs) exposing the (110) facet exhibited the highest oxygen vacancy (O_v) concentration and optimal electrosynthetic performance for alanine. A series of control experiments, electrochemical characterizations, <i>in situ</i> electrochemical attenuated total reflection Fourier transform infrared spectroscopy (<i>in situ</i> ATR-FTIR), online electrochemical differential mass spectrometry (DEMS), quasi <i>in situ</i> electron paramagnetic resonance (quasi <i>in situ</i> EPR) experiments, combined with density functional theory (DFT) calculations indicated that the synthesis pathway for alanine involved the reduction of NO₃ ^- to produce ^*NH₂OH <i>in situ</i>, which nucleophilically attacked the carbonyl group of pyruvate to form the key intermediate species, oxime, then underwent further amination to generate alanine. The key step responsible for the performance difference of four CeO₂ nanocrystals lay in the reduction amination of pyruvate oxime (PO), confirming the (110) facet with more O_v exposure facilitated the cleavage of the N-O bond in pyruvate oxime (^*OOC(H₃C)C=N-OH→^*OOC(H₃C)C=N), while also lowering the energy consumption for the hydrogenation of the C=N bond (^*OOC(H₃C)C=NH→^*OOC(H₃C)CNH₂). This innovative strategy not only provides a new route for the valorization of biomass and waste nitrate but also offers valuable guidance for the design of more efficient rare-earth-based catalysts in this field.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"2015-2026"},"PeriodicalIF":8.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045801","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":"Effect of Pyridinecarboxaldehyde Functionalization on Reactivity and N-Terminal Protein Modification.","authors":"Lydia J Barber, Ksenia S Stankevich, Christopher D Spicer","doi":"10.1021/jacsau.5c00238","DOIUrl":"https://doi.org/10.1021/jacsau.5c00238","url":null,"abstract":"<p><p>The site-selective modification of protein N-termini represents a powerful strategy for producing homogeneous bioconjugates. 2-Pyridinecarboxaldehydes have emerged as a leading reagent class in this area. However, these conjugations suffer from relatively slow rates and a degree of reversibility. In this work, we therefore studied the effects of pyridinecarboxaldehyde functionalization on N-terminal modification. This allowed us to provide insight into the factors governing relative contributions from competing reaction pathways and design criteria for second generation reagents for protein labeling. Importantly, 3-methoxy-2-pyridinecarboxaldehydes were identified as providing both accelerated and more stable protein labeling, enabling further applications of this powerful technology.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 4","pages":"1983-1991"},"PeriodicalIF":8.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055612","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":"Palladium-Catalyzed Functionalization of Shortwave Infrared Heptamethine Fluorophores Expands Their In Vivo Utility.","authors":"Cesar A Garcia, Emily B Mobley, Eric Y Lin, Kyle Bui, Ellen M Sletten","doi":"10.1021/jacsau.4c01279","DOIUrl":"10.1021/jacsau.4c01279","url":null,"abstract":"<p><p>Fluorescence imaging in the near-infrared (NIR, 700-1000 nm) and shortwave infrared (SWIR, 1000-2000 nm) regions is advantageous for studying mammals. This work applies palladium-catalyzed coupling methods to functionalize flavylium and chromenylium SWIR polymethine fluorophores, which are challenging substrates due to their small HOMO-LUMO gaps. These chemistries include Suzuki-Miyaura and Sonogashira couplings as well as an unprecedented coupling of alcohol substrates to ultimately achieve a panel of C-C_Ar, C-C_sp, and C-O-alkyl functionalized SWIR fluorescent heptamethine dyes. The photophysical properties of the resulting fluorophores are analyzed against Hammett parameters to produce predictive metrics for absorption maxima. These metrics are strategically applied in the design of laser-matched, SWIR-emissive, chromenylium heptamethine dyes. Added functionalities advance the utility of SWIR fluorophores by increasing brightness in micelle formulations, modulating lipophilicity for alternative delivery vehicles, and enabling bioconjugation to targeting moieties. Ultimately, three functionalized fluorophores are employed in concert to achieve multicolor excitation-multiplexed imaging in murine cancer models.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2089-2101"},"PeriodicalIF":8.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183233","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}