JACS Au最新文献 - Book学术

Polymers for the Clean Energy Transition

IF 8.5

JACS Au Pub Date : 2024-12-23 DOI: 10.1021/jacsau.4c0115210.1021/jacsau.4c01152

Emily C. Davidson*, He Tian* and Rodney D. Priestley*,

引用次数: 0

Electrochemical Biosensors for Cancer Diagnosis: Multitarget Analysis to Present Molecular Characteristics of Tumor Heterogeneity

IF 8.5

JACS Au Pub Date : 2024-12-11 DOI: 10.1021/jacsau.4c0098910.1021/jacsau.4c00989

Ya Cao, Jianan Xia, Lijuan Li, Yujing Zeng, Jing Zhao* and Genxi Li*,

{"title":"Electrochemical Biosensors for Cancer Diagnosis: Multitarget Analysis to Present Molecular Characteristics of Tumor Heterogeneity","authors":"Ya Cao, Jianan Xia, Lijuan Li, Yujing Zeng, Jing Zhao* and Genxi Li*, ","doi":"10.1021/jacsau.4c0098910.1021/jacsau.4c00989","DOIUrl":"https://doi.org/10.1021/jacsau.4c00989https://doi.org/10.1021/jacsau.4c00989","url":null,"abstract":"Electrochemical biosensors are gaining attention as powerful tools in cancer diagnosis, particularly in liquid biopsy, due to their high efficiency, rapid response, exceptional sensitivity, and specificity. However, the complexity of intra- and intertumor heterogeneity, with variations in genetic and protein expression profiles and epigenetic modifications, makes electrochemical biosensors susceptible to false-positive or false-negative diagnostic outcomes. To address this challenge, there is growing interest in simultaneously analyzing multiple biomarkers to reveal molecular characteristics of tumor heterogeneity for precise cancer diagnosis. In this Perspective, we highlight recent advancements in utilizing electrochemical biosensors for cancer diagnosis, with a specific emphasis on the multitarget analysis of cancer biomarkers including tumor-associated nucleic acids, tumor protein markers, extracellular vesicles, and tumor cells. These biosensors hold significant promise for improving precision in early cancer diagnosis and monitoring, as well as potentially offering new insights into personalized cancer management.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4655–4672 4655–4672"},"PeriodicalIF":8.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00989","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870155","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}

引用次数: 0

Electrochemical Synthesis of Zeolite Coatings with Controlled Crystal Polymorphism and Self-Regulating Growth

IF 8.5

JACS Au Pub Date : 2024-12-10 DOI: 10.1021/jacsau.4c0069110.1021/jacsau.4c00691

Akash Warty, Amy Chen, Dat T. Tran, Harrison Kraus, Taylor J. Woehl and Dongxia Liu*,

{"title":"Electrochemical Synthesis of Zeolite Coatings with Controlled Crystal Polymorphism and Self-Regulating Growth","authors":"Akash Warty, Amy Chen, Dat T. Tran, Harrison Kraus, Taylor J. Woehl and Dongxia Liu*, ","doi":"10.1021/jacsau.4c0069110.1021/jacsau.4c00691","DOIUrl":"https://doi.org/10.1021/jacsau.4c00691https://doi.org/10.1021/jacsau.4c00691","url":null,"abstract":"Zeolite coatings are studied as molecular sieves for membrane separation, membrane reactors, and chemical sensor applications. They are also studied as anticorrosive films for metals and alloys, antimicrobial and hydrophobic films for heating, ventilation, and air conditioning, and dielectrics for semiconductor applications. Zeolite coatings are synthesized by hydrothermal, ionothermal, and dry-gel conversion approaches, which require high process temperatures and lengthy times (ranging from hours to days). Here, we report the first zeolite coatings synthesized via electrochemical deposition on a cathodic electrode, with controlled crystal polymorphism achieved within subhourly duration. We demonstrate this approach by developing sodium zeolite (e.g., sodalite (SOD), NaA (LTA), and Linde Type N (LTN)) coatings on a titanium electrode and extending the synthesis method to porous stainless steel. The coating morphology and crystallinity depend on the temperature, time, and applied current. The coating thickness is independent of the applied current, showing the presence of a self-regulating mechanism to ensure a uniform coating thickness across the metal surface. The electrochemical zeolite growth mechanism was elucidated with high-resolution transmission electron microscopy, and applications of the resultant zeolite coatings for oil/water separation and ethanol/water pervaporation were exploited. Electrochemical synthesis represents a novel, simple, fast, and environmentally friendly approach to preparing zeolite coatings. It can potentially be generalized for developing zeolite materials with diverse framework structures, morphologies, and orientations for substrates with complicated geometries.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4769–4779 4769–4779"},"PeriodicalIF":8.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874984","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}

引用次数: 0

Proton Tunneling Allows a Proton-Coupled Electron Transfer Process in the Cancer Cell

IF 8.5

JACS Au Pub Date : 2024-12-10 DOI: 10.1021/jacsau.4c0081510.1021/jacsau.4c00815

Tong Zhang, Arindam Ghosh, Lisa Behringer-Pließ, Lata Chouhan, Ana V. Cunha, Remco W. A. Havenith, Eugenia Butkevich, Lei Zhang, Olalla Vázquez, Elke Debroye, Jörg Enderlein* and Shoubhik Das*,

{"title":"Proton Tunneling Allows a Proton-Coupled Electron Transfer Process in the Cancer Cell","authors":"Tong Zhang, Arindam Ghosh, Lisa Behringer-Pließ, Lata Chouhan, Ana V. Cunha, Remco W. A. Havenith, Eugenia Butkevich, Lei Zhang, Olalla Vázquez, Elke Debroye, Jörg Enderlein* and Shoubhik Das*, ","doi":"10.1021/jacsau.4c0081510.1021/jacsau.4c00815","DOIUrl":"https://doi.org/10.1021/jacsau.4c00815https://doi.org/10.1021/jacsau.4c00815","url":null,"abstract":"Proton-coupled electron transfer (PCET) is a fundamental redox process and has clear advantages in selectively activating challenging C–H bonds in many biological processes. Intrigued by this activation process, we aimed to develop a facile PCET process in cancer cells by modulating proton tunneling. This approach should lead to the design of an alternative photodynamic therapy (PDT) that depletes the mitochondrial electron transport chain (ETC), the key redox regulator in cancer cells under hypoxia. To observe this depletion process in the cancer cell, we monitored the oxidative-stress-induced depolarization of mitochondrial inner membrane potential (MMP) using fluorescence lifetime imaging microscopy (FLIM). Typically, increasing metabolic stress of cancer cells is reflected in a nontrivial change in the fluorophore’s fluorescence lifetime. After 30 min of irradiation, we observed a shift in the mean lifetime value and a drastic drop in overall fluorescence signal. In addition, our PCET strategy resulted in drastic reorganization of mitochondrial morphology from tubular to vesicle-like and causing an overall depletion of intact mitochondria in the hypodermis of C. elegans. These observations confirmed that PCET promoted ROS-induced oxidative stress. Finally, we gained a clear understanding of the proton tunneling effect in the PCET process through photoluminescence experiments and DFT calculations.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4856–4865 4856–4865"},"PeriodicalIF":8.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874985","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}

引用次数: 0

Quantitative Characterization of Partitioning Stringency in SELEX

IF 8.5

JACS Au Pub Date : 2024-12-09 DOI: 10.1021/jacsau.4c0089010.1021/jacsau.4c00890

An T. H. Le, Eden Teclemichael, Svetlana M. Krylova and Sergey N. Krylov*,

{"title":"Quantitative Characterization of Partitioning Stringency in SELEX","authors":"An T. H. Le, Eden Teclemichael, Svetlana M. Krylova and Sergey N. Krylov*, ","doi":"10.1021/jacsau.4c0089010.1021/jacsau.4c00890","DOIUrl":"https://doi.org/10.1021/jacsau.4c00890https://doi.org/10.1021/jacsau.4c00890","url":null,"abstract":"Maintaining stringent conditions in SELEX (Systematic Evolution of Ligands by EXponential enrichment) is crucial for obtaining high-affinity aptamers. However, excessive stringency greatly increases the risk of SELEX failure. Controlling stringency has remained a technical challenge, largely dependent on intuition, due to the absence of a clear, quantitative measure of stringency. This study was motivated by our insight that, while stringency is influenced by multiple factors, it can be quantified by its effect: increasing stringency reduces the quantity of binders normalized to that of nonbinders after partitioning. Based on this insight, we propose measuring stringency using the binder-to-nonbinder ratio (BNR), where a lower BNR indicates higher stringency. We derive an experimental method for determining BNR via quantitative PCR. Our theoretical analysis and SELEX experiments using two distinct proteins as selection targets underscore the importance of maintaining a BNR significantly greater than zero to avoid failure, a principle we call the SELEX nonfailure criterion. By employing inverse BNR to quantify stringency and applying this criterion, researchers can more rationally control SELEX progress. The quantitative stringency measure and nonfailure criterion can also be applied to other artificial evolution methods, provided that selected binders are quantifiable.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4910–4920 4910–4920"},"PeriodicalIF":8.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00890","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874963","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}

引用次数: 0

Discovery of Spirosnuolides A–D, Type I/III Hybrid Polyketide Spiro-Macrolides for a Chemotherapeutic Lead against Lung Cancer

IF 8.5

JACS Au Pub Date : 2024-12-09 DOI: 10.1021/jacsau.4c0080310.1021/jacsau.4c00803

Thanh-Hau Huynh, Sung Chul Jang, Yeon Hee Ban, Eun-Young Lee, Taeho Kim, Ilnam Kang, Joon Soo An, Sangwook Kang, Jaeho Han, Yun Kwon, Daehyun Oh, Hyeung-geun Park, Jang-Cheon Cho, Jichan Jang, Ki-Bong Oh, Sang-Jip Nam, Sang Kook Lee* and Dong-Chan Oh*,

{"title":"Discovery of Spirosnuolides A–D, Type I/III Hybrid Polyketide Spiro-Macrolides for a Chemotherapeutic Lead against Lung Cancer","authors":"Thanh-Hau Huynh, Sung Chul Jang, Yeon Hee Ban, Eun-Young Lee, Taeho Kim, Ilnam Kang, Joon Soo An, Sangwook Kang, Jaeho Han, Yun Kwon, Daehyun Oh, Hyeung-geun Park, Jang-Cheon Cho, Jichan Jang, Ki-Bong Oh, Sang-Jip Nam, Sang Kook Lee* and Dong-Chan Oh*, ","doi":"10.1021/jacsau.4c0080310.1021/jacsau.4c00803","DOIUrl":"https://doi.org/10.1021/jacsau.4c00803https://doi.org/10.1021/jacsau.4c00803","url":null,"abstract":"Four new macrolides, spirosnuolides A–D (1–4, respectively), were discovered from the termite nest-derived Kitasatospora sp. INHA29. Spirosnuolides A–D are 18-membered macrolides sharing an embedded [6,6]-spiroketal functionality inside the macrocycle and are conjugated with structurally uncommon side chains featuring cyclopentenone, 1,4-benzoquinone, hydroxyfuroic acid, or butenolide moieties. Structure elucidation was achieved using a combination of spectroscopic analyses, multiple chemical derivatizations (methylation, methanolysis, Luche reduction, and Mosher’s reaction), X-ray diffraction analysis, and computational ECD calculations. Interestingly, genome sequencing analysis suggests that spirosnuolides were biosynthesized through a rare type I/III hybrid polyketide synthase. Importantly, spirosnuolide B displayed potent antiproliferative effects against various cancer cell lines at nanomolar concentrations, particularly against HCC827 cells, an EGFR mutant non-small-cell lung cancer (NSCLC) cell line, with a high safety index value. Based on in vitro studies, the antiproliferative mechanism of spirosnuolide B involved the activation of AMPK signaling, leading to cell cycle arrest and apoptosis in HCC827 cells. Its potent efficacy was also proven in vivo by the effective inhibition of tumor growth in mouse xenograft studies. Moreover, cotreatment with spirosnuolide B and gefitinib, synergistically enhanced the antiproliferative activity and apoptosis, suggesting a potential strategy to overcome gefitinib resistance in EGFR mutant NSCLC.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4821–4832 4821–4832"},"PeriodicalIF":8.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00803","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874988","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}

引用次数: 0

Multifunctional Supramolecular Gels with Strong Mechanical Properties Formed by Self-Assembly of Polyoxometalate-Based Coordination Polymers

IF 8.5

JACS Au Pub Date : 2024-12-05 DOI: 10.1021/jacsau.4c0098110.1021/jacsau.4c00981

Lorenzo Casimiro, Florence Volatron, Grégoire Boivin, Benjamin Abécassis, Sandra Alves, Dalil Brouri, David Montero, Jean-Michel Guigner, Lise-Marie Chamoreau, Geoffrey Gontard, David Portehault, Yanling Li, Anna Proust, Rodrigue Lescouëzec, Guylaine Ducouret, Albert Solé-Daura*, Patrick Davidson*, Théo Merland* and Guillaume Izzet*,

{"title":"Multifunctional Supramolecular Gels with Strong Mechanical Properties Formed by Self-Assembly of Polyoxometalate-Based Coordination Polymers","authors":"Lorenzo Casimiro, Florence Volatron, Grégoire Boivin, Benjamin Abécassis, Sandra Alves, Dalil Brouri, David Montero, Jean-Michel Guigner, Lise-Marie Chamoreau, Geoffrey Gontard, David Portehault, Yanling Li, Anna Proust, Rodrigue Lescouëzec, Guylaine Ducouret, Albert Solé-Daura*, Patrick Davidson*, Théo Merland* and Guillaume Izzet*, ","doi":"10.1021/jacsau.4c0098110.1021/jacsau.4c00981","DOIUrl":"https://doi.org/10.1021/jacsau.4c00981https://doi.org/10.1021/jacsau.4c00981","url":null,"abstract":"Metallogels built in a bottom-up approach by metal coordination and supramolecular interactions have important potential for the elaboration of smart materials. In this context, we present here the formation of supramolecular coordination polymers driven by the complexation of cobalt(II) or zinc(II) ions with polyoxometalate-based hybrids displaying two terpyridine ligands in a linear arrangement. Thanks to the electrostatic interactions between the polyoxometalate cores and metal nodes, the polymer chains self-assemble into fibers that physically cross-link to form gels above a critical concentration. Using spectroscopy, microscopy, X-ray scattering, and rheometry, complemented by molecular dynamics simulations, we investigated the supramolecular organization of the chains in the fibers and the resulting processes leading to gelation. Compared to previously reported systems, these gels have improved rheological features and appealing properties, such as birefringence, luminescence, and spin crossover, paving the way for their use as building blocks for multifunctional smart materials.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4948–4956 4948–4956"},"PeriodicalIF":8.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00981","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875056","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}

引用次数: 0

Metal-Independent Correlations for Site-Specific Binding Energies of Relevant Catalytic Intermediates

IF 8.5

JACS Au Pub Date : 2024-12-05 DOI: 10.1021/jacsau.4c0075910.1021/jacsau.4c00759

Shyama Charan Mandal, and , Frank Abild-Pedersen*,

{"title":"Metal-Independent Correlations for Site-Specific Binding Energies of Relevant Catalytic Intermediates","authors":"Shyama Charan Mandal,  and , Frank Abild-Pedersen*, ","doi":"10.1021/jacsau.4c0075910.1021/jacsau.4c00759","DOIUrl":"https://doi.org/10.1021/jacsau.4c00759https://doi.org/10.1021/jacsau.4c00759","url":null,"abstract":"Establishing energy correlations among different metals can accelerate the discovery of efficient and cost-effective catalysts for complex reactions. Using a recently introduced coordination-based model, we can predict site-specific metal binding energies (ΔEM) that can be used as a descriptor for chemical reactions. In this study, we have examined a range of metals including Ag, Au, Co, Cu, Ir, Ni, Os, Pd, Pt, Rh, and Ru and found linear correlations between predicted ΔEM and adsorption energies of CH and O (ΔECH and ΔEO) at various coordination environments for all the considered metals. Interestingly, all the metals correlate with one another under specific surface site coordination, indicating that different metals are interrelated in a particular coordination environment. Furthermore, we have tested and verified for PtPd- and PtIr-based alloys that they follow a similar behavior. Moreover, we have expanded the metal space by taking some early transition metals along with a few s-block metals and shown a cyclic behavior of the adsorbate binding energy (ΔEA) versus ΔEM. Therefore, ΔECH and ΔEO can be efficiently interpolated between metals, alloys, and intermetallics based on information related to one metal only. This simplifies the process of screening new metal catalyst formulations and their reaction energies.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4790–4798 4790–4798"},"PeriodicalIF":8.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870099","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}

引用次数: 0

Hydrogen Bond Blueshifts in Nitrile Vibrational Spectra Are Dictated by Hydrogen Bond Geometry and Dynamics

IF 8.5

JACS Au Pub Date : 2024-12-05 DOI: 10.1021/jacsau.4c0081110.1021/jacsau.4c00811

Jacob M. Kirsh, and , Jacek Kozuch*,

{"title":"Hydrogen Bond Blueshifts in Nitrile Vibrational Spectra Are Dictated by Hydrogen Bond Geometry and Dynamics","authors":"Jacob M. Kirsh,  and , Jacek Kozuch*, ","doi":"10.1021/jacsau.4c0081110.1021/jacsau.4c00811","DOIUrl":"https://doi.org/10.1021/jacsau.4c00811https://doi.org/10.1021/jacsau.4c00811","url":null,"abstract":"Vibrational Stark effect (VSE) spectroscopy has become one of the most important experimental approaches to determine the strength of noncovalent, electrostatic interactions in chemistry and biology and to quantify their influence on structure and reactivity. Nitriles (C≡N) have been widely used as VSE probes, but their application has been complicated by an anomalous hydrogen bond (HB) blueshift which is not encompassed within the VSE framework. We present an empirical model describing the anomalous HB blueshift in terms of H-bonding geometry, i.e., as a function of HB distance and angle with respect to the C≡N group. This model is obtained by comparing vibrational observables from density functional theory and electrostatics from the polarizable AMOEBA force field, and it provides a physical explanation for the HB blueshift in terms of underlying multipolar and Pauli repulsion contributions. Additionally, we compare predicted blueshifts with experimental results and find our model provides a useful, direct framework to analyze HB geometry for rigid HBs, such as within proteins or chemical frameworks. In contrast, nitriles in highly dynamic H-bonding environments like protic solvents are no longer a function solely of geometry; this is a consequence of motional narrowing, which we demonstrate by simulating IR spectra. Overall, when HB geometry and dynamics are accounted for, an excellent correlation is found between observed and predicted HB blueshifts. This correlation includes different types of nitriles and HB donors, suggesting that our model is general and can aid in understanding HB blueshifts wherever nitriles can be implemented.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4844–4855 4844–4855"},"PeriodicalIF":8.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875055","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}

引用次数: 0

DefNEtTrp: An Iron Dual Chelator Approach for Anticancer Application

IF 8.5

JACS Au Pub Date : 2024-12-04 DOI: 10.1021/jacsau.4c0077410.1021/jacsau.4c00774

Israel Rodríguez, Carmen Acosta, Christopher Nieves-Escobar, Estelle Strangmark, Oscar Claudio-Ares, Adriana I. Vargas Figueroa, Alexandra M. Soto-Millán, Aixa M. Orta-Rivera, Andrei V. Astashkin and Arthur D. Tinoco*,

{"title":"DefNEtTrp: An Iron Dual Chelator Approach for Anticancer Application","authors":"Israel Rodríguez, Carmen Acosta, Christopher Nieves-Escobar, Estelle Strangmark, Oscar Claudio-Ares, Adriana I. Vargas Figueroa, Alexandra M. Soto-Millán, Aixa M. Orta-Rivera, Andrei V. Astashkin and Arthur D. Tinoco*, ","doi":"10.1021/jacsau.4c0077410.1021/jacsau.4c00774","DOIUrl":"https://doi.org/10.1021/jacsau.4c00774https://doi.org/10.1021/jacsau.4c00774","url":null,"abstract":"Targeting iron metabolism has emerged as a novel therapeutic strategy for the treatment of cancer. As such, iron chelator drugs are repurposed or specifically designed as anticancer agents. Two important chelators, deferasirox (Def) and triapine (Trp), attack the intracellular supply of iron (Fe) and inhibit Fe-dependent pathways responsible for cellular proliferation and metastasis. Trp, in particular, forms a redox active ferrous complex that inactivates the Fe-dependent ribonucleotide reductase (RNR), responsible for DNA replication. Building on recent efforts to employ intracellular Fe chelation for anticancer therapy, this work aimed to develop the Fe dual chelator ligand DefNEtTrp, consisting of the Def and Trp moieties, to exploit their high affinity Fe(II/III) binding and redox modulation. Using UV–vis spectroscopy, EPR spectroscopy, ESI and MALDI-TOF mass spectrometry, and cyclic voltammetry analyses, DefNEtTrp is shown to retain its Fe binding at both chelator moieties and generate a redox active Fe(III) complex Fe3(DefNEtTrp)2 featuring a reduction potential (E1/2 = +0.103 V vs normal hydrogen electrode) within the biological window. Screened against different cancer cell line types, DefNEtTrp exhibits potent and broad-spectrum antiproliferative and cell death behavior. Its cytotoxicity (IC50 0.77 ± 0.06 μM) is superior to that of unconjugated Def and Trp ligands (IC50 2.6 ± 0.15 μM and 1.1 ± 0.04 μM, respectively) in single-compound and combination treatments and is selective toward cancer cells. The cell death mechanism of the dual chelator is assessed in the context of intracellular labile Fe binding and was found to induce both apoptosis and ferroptosis.","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"4 12","pages":"4799–4808 4799–4808"},"PeriodicalIF":8.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.4c00774","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875050","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}

引用次数: 0