JACS AuPub Date : 2025-05-12eCollection Date: 2025-05-26DOI: 10.1021/jacsau.5c00058
Weiming Lin, Tao Ding, Die He, Nan Zhang, Haodong Li, Wenjian Luo, Zhongxia Wei, Min Ke, Sisi Jia, Chunhai Fan, Le Liang
{"title":"DNA Logic-Integrated Quantum Nanosensor for MicroRNA Diagnostics.","authors":"Weiming Lin, Tao Ding, Die He, Nan Zhang, Haodong Li, Wenjian Luo, Zhongxia Wei, Min Ke, Sisi Jia, Chunhai Fan, Le Liang","doi":"10.1021/jacsau.5c00058","DOIUrl":"https://doi.org/10.1021/jacsau.5c00058","url":null,"abstract":"<p><p>Nanodiamonds (NDs) with nitrogen-vacancy (NV) centers are emerging as powerful quantum nanosensors (QNs) in biomedical applications due to their exceptional sensitivity. However, achieving optimal diagnostics performance necessitates both high sensitivity and selectivity; especially in practical biomedical settings, it remains challenging for QNs to provide quantitative analyses when multiple analytes are present. Here, we present a biosensing platform that integrates DNA logic gates (DLGs) with spin-based quantum sensing, termed DLG-QN for ultrasensitive and ultraselective diagnostics. Utilizing an AND DLG, both NDs and magnetic beads (MBs) are functionalized with hairpin DNA strands. In the presence of both miRNA-21 and miRNA-155key biomarkers overexpressed in cancerthe hairpin DNAs undergo conformational changes that facilitate DNA-guided self-assembly of NDs and MBs, enriching the target signal. Resonant microwave modulation of ND fluorescence emission allows for high signal-to-noise ratio (SNR) detection by separating the signal from background fluorescence via spin-enhanced analysis. This platform demonstrated ultrasensitive and ultraselective detection of miRNA-21 and miRNA-155 with a limit of detection of 19.8 fM, highlighting its potential as a general biosensing strategy for precision diagnostics involving multiple biomarkers.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2123-2134"},"PeriodicalIF":8.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182700","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}
JACS AuPub Date : 2025-05-12DOI: 10.1021/jacsau.5c0005810.1021/jacsau.5c00058
Weiming Lin, Tao Ding, Die He, Nan Zhang, Haodong Li, Wenjian Luo, Zhongxia Wei, Min Ke, Sisi Jia*, Chunhai Fan and Le Liang*,
{"title":"DNA Logic-Integrated Quantum Nanosensor for MicroRNA Diagnostics","authors":"Weiming Lin, Tao Ding, Die He, Nan Zhang, Haodong Li, Wenjian Luo, Zhongxia Wei, Min Ke, Sisi Jia*, Chunhai Fan and Le Liang*, ","doi":"10.1021/jacsau.5c0005810.1021/jacsau.5c00058","DOIUrl":"https://doi.org/10.1021/jacsau.5c00058https://doi.org/10.1021/jacsau.5c00058","url":null,"abstract":"<p >Nanodiamonds (NDs) with nitrogen-vacancy (NV) centers are emerging as powerful quantum nanosensors (QNs) in biomedical applications due to their exceptional sensitivity. However, achieving optimal diagnostics performance necessitates both high sensitivity and selectivity; especially in practical biomedical settings, it remains challenging for QNs to provide quantitative analyses when multiple analytes are present. Here, we present a biosensing platform that integrates DNA logic gates (DLGs) with spin-based quantum sensing, termed DLG-QN for ultrasensitive and ultraselective diagnostics. Utilizing an AND DLG, both NDs and magnetic beads (MBs) are functionalized with hairpin DNA strands. In the presence of both miRNA-21 and miRNA-155─key biomarkers overexpressed in cancer─the hairpin DNAs undergo conformational changes that facilitate DNA-guided self-assembly of NDs and MBs, enriching the target signal. Resonant microwave modulation of ND fluorescence emission allows for high signal-to-noise ratio (SNR) detection by separating the signal from background fluorescence via spin-enhanced analysis. This platform demonstrated ultrasensitive and ultraselective detection of miRNA-21 and miRNA-155 with a limit of detection of 19.8 fM, highlighting its potential as a general biosensing strategy for precision diagnostics involving multiple biomarkers.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2123–2134 2123–2134"},"PeriodicalIF":8.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133969","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":"Formation of a Pd<sub>16</sub> Molecular Basket Architecture of Reduced Symmetry and Angular Deviation in a Fluorenone Scaffold to Govern the Host-Guest Chemistry of Pd<sub>6</sub> Trifacial Tubes.","authors":"Medha Aggarwal, Ranit Banerjee, Neal Hickey, Partha Sarathi Mukherjee","doi":"10.1021/jacsau.5c00390","DOIUrl":"https://doi.org/10.1021/jacsau.5c00390","url":null,"abstract":"<p><p>The employment of flexible ligands with significant conformational freedom in coordination-driven self-assembly enables the formation of unique and intricate structures. In this study, the self-assembly of such a fluorenone-appended ligand (<b>L1</b>) with a sterically demanding acceptor, [Pd-(tmed)-(ONO<sub>2</sub>)<sub>2</sub>] (<b>M1</b>), generated a new and unique molecular basket architecture, (<b>M1</b>) <b><sub>16</sub></b> (<b>L1</b>) <b><sub>8</sub></b> (<b>B</b>), featuring a large hollow cavity. <b>B</b> possesses an unusual twisted architecture of low symmetry, consisting of 16 Pd-(II) centers arranged as four tetrahedra connected by eight flexible ligands, representing a structurally complex system reminiscent of biological architectures. Designing such entropically disfavored, large architectures of reduced symmetry is challenging but desirable, since they can act as ideal models to study complicated natural systems. The host-guest property of supramolecular hosts is governed by the confined cavities and noncovalent interactions, which are dictated by the angular disposition of ligand coordination sites. To explore this, the fluorenone scaffold was used to synthesize two other tetradentate ligands (<b>L2</b> and <b>L3</b>) that differed in the spatial distributions of their coordination vectors. The self-assembly of these ligands with [Pd-(en)-(ONO<sub>2</sub>)<sub>2</sub>] (<b>M2</b>) resulted in the formation of water-soluble (<b>M2</b>) <b><sub>6</sub></b> (<b>L1</b>/<b>L2</b>/<b>L3</b>) <b><sub>3</sub></b> trifacial tubes of different geometries with varying internal cavity dimensions. These angular variations further altered the orientation of the fluorenone carbonyl groups within the cavities, thereby modulating their guest binding abilities and highlighting the importance of tailoring supramolecular hosts for specific guest binding.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2368-2378"},"PeriodicalIF":8.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183535","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}
JACS AuPub Date : 2025-05-09DOI: 10.1021/jacsau.5c0039010.1021/jacsau.5c00390
Medha Aggarwal, Ranit Banerjee, Neal Hickey and Partha Sarathi Mukherjee*,
{"title":"Formation of a Pd16 Molecular Basket Architecture of Reduced Symmetry and Angular Deviation in a Fluorenone Scaffold to Govern the Host–Guest Chemistry of Pd6 Trifacial Tubes","authors":"Medha Aggarwal, Ranit Banerjee, Neal Hickey and Partha Sarathi Mukherjee*, ","doi":"10.1021/jacsau.5c0039010.1021/jacsau.5c00390","DOIUrl":"https://doi.org/10.1021/jacsau.5c00390https://doi.org/10.1021/jacsau.5c00390","url":null,"abstract":"<p >The employment of flexible ligands with significant conformational freedom in coordination-driven self-assembly enables the formation of unique and intricate structures. In this study, the self-assembly of such a fluorenone-appended ligand (<b>L1</b>) with a sterically demanding acceptor, [Pd(tmed)(ONO<sub>2</sub>)<sub>2</sub>] (<b>M1</b>), generated a new and unique molecular basket architecture, (<b>M1</b>)<b><sub>16</sub></b>(<b>L1</b>)<b><sub>8</sub></b> (<b>B</b>), featuring a large hollow cavity. <b>B</b> possesses an unusual twisted architecture of low symmetry, consisting of 16 Pd(II) centers arranged as four tetrahedra connected by eight flexible ligands, representing a structurally complex system reminiscent of biological architectures. Designing such entropically disfavored, large architectures of reduced symmetry is challenging but desirable, since they can act as ideal models to study complicated natural systems. The host–guest property of supramolecular hosts is governed by the confined cavities and noncovalent interactions, which are dictated by the angular disposition of ligand coordination sites. To explore this, the fluorenone scaffold was used to synthesize two other tetradentate ligands (<b>L2</b> and <b>L3</b>) that differed in the spatial distributions of their coordination vectors. The self-assembly of these ligands with [Pd(en)(ONO<sub>2</sub>)<sub>2</sub>] (<b>M2</b>) resulted in the formation of water-soluble (<b>M2</b>)<b><sub>6</sub></b>(<b>L1</b>/<b>L2</b>/<b>L3</b>)<b><sub>3</sub></b> trifacial tubes of different geometries with varying internal cavity dimensions. These angular variations further altered the orientation of the fluorenone carbonyl groups within the cavities, thereby modulating their guest binding abilities and highlighting the importance of tailoring supramolecular hosts for specific guest binding.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2368–2378 2368–2378"},"PeriodicalIF":8.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134045","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}
JACS AuPub Date : 2025-05-09DOI: 10.1021/jacsau.5c0014610.1021/jacsau.5c00146
Yu-Kai Cheng, Hsing-Hui Chu, Ning-Jun Yang and Yei-Chen Lai*,
{"title":"Decoupling Global and Local Structural Changes in Self-aminoacylating Ribozymes Reveals the Critical Role of Local Structural Dynamics in Ribozyme Activity","authors":"Yu-Kai Cheng, Hsing-Hui Chu, Ning-Jun Yang and Yei-Chen Lai*, ","doi":"10.1021/jacsau.5c0014610.1021/jacsau.5c00146","DOIUrl":"https://doi.org/10.1021/jacsau.5c00146https://doi.org/10.1021/jacsau.5c00146","url":null,"abstract":"<p >Self-aminoacylating ribozymes catalyze the attachment of amino acids to RNA, serving as pivotal models to investigate the catalytic roles of RNA in prebiotic evolution. In this study, we investigated how divalent metal ions (Mg<sup>2+</sup> and Ca<sup>2+</sup>) modulate local and global structures in two such ribozymes, S-1A.1-a and S-2.1-a, using 4-cyanotryptophan (4CNW) fluorescence and native gel electrophoresis. By tracking 4CNW fluorescence changes at varying concentrations of Mg<sup>2+</sup> and Ca<sup>2+</sup> and temperatures, we determined how these ions influence the catalytic sites and overall conformations of the ribozymes. Our findings reveal that Mg<sup>2+</sup> specifically binds to S-1A.1-a at low concentrations, stabilizing the local structure around the aminoacylation site and causing the site to become more buried, which is essential for catalytic activity. Although higher Mg<sup>2+</sup> and Ca<sup>2+</sup> concentrations induce global structural rearrangements, these shifts have minimal impact on the local environment of the aminoacylation site, underscoring the dominance of local structural stability in sustaining ribozyme function. In contrast, the activity of S-2.1-a effectively adapts to both Mg<sup>2+</sup> and Ca<sup>2+</sup>, and its fluorescence results indicate a more solvent-exposed aminoacylation site. Overall, these data highlight that local structural changes in the ribozyme’s catalytic core are more critical for its function than global conformational shifts. Our study highlights the importance of local environmental changes in ion-dependent ribozyme catalysis and provides insights into the molecular mechanisms of self-aminoacylating ribozymes.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2172–2185 2172–2185"},"PeriodicalIF":8.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134007","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}
JACS AuPub Date : 2025-05-09eCollection Date: 2025-05-26DOI: 10.1021/jacsau.5c00146
Yu-Kai Cheng, Hsing-Hui Chu, Ning-Jun Yang, Yei-Chen Lai
{"title":"Decoupling Global and Local Structural Changes in Self-aminoacylating Ribozymes Reveals the Critical Role of Local Structural Dynamics in Ribozyme Activity.","authors":"Yu-Kai Cheng, Hsing-Hui Chu, Ning-Jun Yang, Yei-Chen Lai","doi":"10.1021/jacsau.5c00146","DOIUrl":"https://doi.org/10.1021/jacsau.5c00146","url":null,"abstract":"<p><p>Self-aminoacylating ribozymes catalyze the attachment of amino acids to RNA, serving as pivotal models to investigate the catalytic roles of RNA in prebiotic evolution. In this study, we investigated how divalent metal ions (Mg<sup>2+</sup> and Ca<sup>2+</sup>) modulate local and global structures in two such ribozymes, S-1A.1-a and S-2.1-a, using 4-cyanotryptophan (4CNW) fluorescence and native gel electrophoresis. By tracking 4CNW fluorescence changes at varying concentrations of Mg<sup>2+</sup> and Ca<sup>2+</sup> and temperatures, we determined how these ions influence the catalytic sites and overall conformations of the ribozymes. Our findings reveal that Mg<sup>2+</sup> specifically binds to S-1A.1-a at low concentrations, stabilizing the local structure around the aminoacylation site and causing the site to become more buried, which is essential for catalytic activity. Although higher Mg<sup>2+</sup> and Ca<sup>2+</sup> concentrations induce global structural rearrangements, these shifts have minimal impact on the local environment of the aminoacylation site, underscoring the dominance of local structural stability in sustaining ribozyme function. In contrast, the activity of S-2.1-a effectively adapts to both Mg<sup>2+</sup> and Ca<sup>2+</sup>, and its fluorescence results indicate a more solvent-exposed aminoacylation site. Overall, these data highlight that local structural changes in the ribozyme's catalytic core are more critical for its function than global conformational shifts. Our study highlights the importance of local environmental changes in ion-dependent ribozyme catalysis and provides insights into the molecular mechanisms of self-aminoacylating ribozymes.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2172-2185"},"PeriodicalIF":8.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182708","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}
JACS AuPub Date : 2025-05-08DOI: 10.1021/jacsau.5c0035210.1021/jacsau.5c00352
Roushan Prakash Singh, and , Neal P. Mankad*,
{"title":"Molecular Design of Al(II) Intermediates for Small Molecule Activation","authors":"Roushan Prakash Singh, and , Neal P. Mankad*, ","doi":"10.1021/jacsau.5c0035210.1021/jacsau.5c00352","DOIUrl":"https://doi.org/10.1021/jacsau.5c00352https://doi.org/10.1021/jacsau.5c00352","url":null,"abstract":"<p >Promoting societally important small molecule activation processes with earth-abundant metals is foundational for a sustainable chemistry future. In this context, mapping new reaction pathways that would enable abundant main-group elements to mimic the behaviors of <i>d</i>- and <i>f</i>-block elements is facilitated by exploring unusual oxidation states. The most abundant metal on earth, aluminum, has been well studied in the Lewis acidic +III and Lewis basic +I oxidation states but rarely in the potentially biphilic +II oxidation state until recently, when a renaissance of Al(II) chemistry emerged from a range of research groups. In this Perspective, we review the chemistry of mononuclear Al radicals, including both Al-centered radicals (i.e., Al(II) compounds) and redox non-innocent systems (i.e., formally Al(II) species that are physically Al(III) with ligand-centered radicals), with an emphasis on small molecule reactivity. We also provide a meta-analysis of the Al(II) literature to summarize how different design strategies (e.g., redox non-innocence, strained coordination geometries) have been shown to impart biphilic character to Al radicals and tune their behavior, thus allowing Al radicals to mimic the chemistry of certain <i>d</i>- and <i>f</i>-block metal ions such as Ti(III) and Sm(II). We expect these molecular design concepts to inform future Al(II) studies as the chemistry of this unusual oxidation state of Al continues to grow.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2076–2088 2076–2088"},"PeriodicalIF":8.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00352","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133919","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}
JACS AuPub Date : 2025-05-08eCollection Date: 2025-05-26DOI: 10.1021/jacsau.5c00352
Roushan Prakash Singh, Neal P Mankad
{"title":"Molecular Design of Al(II) Intermediates for Small Molecule Activation.","authors":"Roushan Prakash Singh, Neal P Mankad","doi":"10.1021/jacsau.5c00352","DOIUrl":"https://doi.org/10.1021/jacsau.5c00352","url":null,"abstract":"<p><p>Promoting societally important small molecule activation processes with earth-abundant metals is foundational for a sustainable chemistry future. In this context, mapping new reaction pathways that would enable abundant main-group elements to mimic the behaviors of <i>d</i>- and <i>f</i>-block elements is facilitated by exploring unusual oxidation states. The most abundant metal on earth, aluminum, has been well studied in the Lewis acidic +III and Lewis basic +I oxidation states but rarely in the potentially biphilic +II oxidation state until recently, when a renaissance of Al-(II) chemistry emerged from a range of research groups. In this Perspective, we review the chemistry of mononuclear Al radicals, including both Al-centered radicals (i.e., Al-(II) compounds) and redox non-innocent systems (i.e., formally Al-(II) species that are physically Al-(III) with ligand-centered radicals), with an emphasis on small molecule reactivity. We also provide a meta-analysis of the Al-(II) literature to summarize how different design strategies (e.g., redox non-innocence, strained coordination geometries) have been shown to impart biphilic character to Al radicals and tune their behavior, thus allowing Al radicals to mimic the chemistry of certain <i>d</i>- and <i>f</i>-block metal ions such as Ti-(III) and Sm-(II). We expect these molecular design concepts to inform future Al-(II) studies as the chemistry of this unusual oxidation state of Al continues to grow.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2076-2088"},"PeriodicalIF":8.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183536","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":"Characterizing the Membrane Assembly of ASGPR Related to Mediated Endocytosis Using TriGalNAc-Probe-Based Super-Resolution Imaging.","authors":"Junling Chen, Jiaqi Wang, Binglin Sui, Pengwei Jiang, Xumin Wang, Hongda Wang, Feng Liang","doi":"10.1021/jacsau.5c00193","DOIUrl":"https://doi.org/10.1021/jacsau.5c00193","url":null,"abstract":"<p><p>The asialoglycoprotein receptor (ASGPR) is a promising therapeutic target for drug delivery systems in hepatocellular carcinoma (HCC), exhibiting high affinity for specific carbohydrate residues and overexpression on malignant hepatic cells. However, their functional mechanisms remain poorly resolved at the single molecule level, hindering the rational optimization of ASGPR-targeted drug delivery systems. Here, we developed a trivalent <i>N</i>-acetylgalactosamine (TriGalNAc)-functionalized ligand probe leveraging high affinity to enable the nanoscale visualization of ASGPR organization and trafficking via super-resolution imaging. Fixed cell imaging revealed pronounced clustering patterns of the ASGPR on HCC membranes. In live cell experiments, we observed the distribution changes of residual ASGPR and returned ASGPR on the membrane during endocytosis, identifying protein clusters as key functional platforms for mediated ligand uptake. Additionally, comparisons with ligand probe binding under varying cell states confirmed that ASGPR aggregation degree correlates with its ligand-binding capacity. Strikingly, disruption of membrane carbohydrate cross-linking dispersed ASGPR clusters and attenuated ligand binding. These findings resolve the nanoscale assembly of ASGPR in HCC and unveil clustering-dependent ligand-binding regulation, advancing a fundamental understanding of ASGPR biology while providing new insights to refine receptor-targeted therapeutics.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2246-2256"},"PeriodicalIF":8.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12117444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183440","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}
JACS AuPub Date : 2025-05-07DOI: 10.1021/jacsau.5c0005910.1021/jacsau.5c00059
Faycel Djebbar, Lise-Marie Chamoreau and Guillaume Lefèvre*,
{"title":"Influence of a Two-Fold Ligation Pattern on Iron-Mediated Aryl–Heteroaryl Cross-Electrophile Couplings","authors":"Faycel Djebbar, Lise-Marie Chamoreau and Guillaume Lefèvre*, ","doi":"10.1021/jacsau.5c0005910.1021/jacsau.5c00059","DOIUrl":"https://doi.org/10.1021/jacsau.5c00059https://doi.org/10.1021/jacsau.5c00059","url":null,"abstract":"<p >An aryl–heteroaryl cross-electrophile coupling (XEC) relying on the use of a single, well-defined iron catalyst is disclosed, involving magnesium as an electron source as well as heteroaryl chlorides and aryl iodides or bromides as coupling partners. A 2-fold coordination pattern featuring a π-acceptor, redox-active (N,N) ligand, along with a σ-donating phosphine ensures both the two-electron reduction of the starting iron(II) precursor to enter the cycle and access to stable organoiron(II) resting states, inhibiting the reductive decomposition of the catalyst.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 5","pages":"2135–2147 2135–2147"},"PeriodicalIF":8.5,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/jacsau.5c00059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133933","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}