{"title":"Reactivity-Guided Selective Covalent Targeting of mtDNA over nDNA by an NHC–Rhenium Complex Triggers Bioenergetic Collapse in Cancer Cells","authors":"Amlanjyoti Dutta, Shubhangi Das, Sushanta Chhatar, Parth Sarathi Nayak, Subhadeep Paul, Srinidhi Srinivasan, Malay Patra","doi":"10.1021/jacsau.6c00579","DOIUrl":"https://doi.org/10.1021/jacsau.6c00579","url":null,"abstract":"<p>Mitochondrial DNA (mtDNA) has emerged as a promisingtarget forthe development of next-generation chemotherapeutics, as its damagecan disrupt key processes that drive cancer progression and resistanceto nuclear DNA (nDNA)-targeting drugs. However, achieving selectiveand direct targeting of mtDNA remains a significant challenge dueto its nucleobase similarity to nDNA and necessitates mitochondria-directeddelivery strategies. This study reports the identification of a novelN-heterocyclic carbene (NHC) rhenium (Re) complex <strong>4</strong> thatselectively targets and damages mtDNA in cancer cells without theneed for mitochondria-directed delivery, while sparing nDNA. Thisremarkable selectivity arises from the inherent reactivity preferenceof this complex toward mtDNA, rather than from distribution-driveneffects. The in vitro potency of complex <strong>4</strong> outperformedthat of nDNA-targeting cisplatin. In-depth mechanistic studies revealedthat complex <strong>4</strong> forms covalent adducts with mtDNA, leadingto disruption of mitochondrial gene replication and transcription.This triggers various downstream effects, including mitochondrialsuperoxide generation, dissipation of membrane potential, downregulationof nucleoid-associated proteins and polymerase γ expression,and depletion of OXPHOS proteins and ATP, leading to induction ofmitophagy and endoplasmic reticulum stress. It induced necroptosis-mediatedcell death and has the ability to overcome cisplatin resistance acrossmultiple cancer cell lines. Furthermore, it significantly reducesthe volume of 3D tumor spheroids, demonstrating efficacy in a physiologicallyrelevant tumor model. Overall, this study identifies for the firsttime the unique mtDNA-targeting capability of [Re(I)(bisNHC)(CO)<sub>3</sub>Cl] complexes without the need for mitochondria-targetingvectors.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"4993–5009"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JACS AuPub Date : 2026-09-28Epub Date: 2026-09-07DOI: 10.1021/jacsau.6c01084
Hyerim Seo, Eunhye Park, Kyeongmee Lee, Juyeon Yoo, Jwa-Min Nam
{"title":"Plasmonic Nanoparticle-Metal–Organic Framework Hybrid Nanostructures for Biomedical Applications: From Design to Function","authors":"Hyerim Seo, Eunhye Park, Kyeongmee Lee, Juyeon Yoo, Jwa-Min Nam","doi":"10.1021/jacsau.6c01084","DOIUrl":"https://doi.org/10.1021/jacsau.6c01084","url":null,"abstract":"<p>Plasmonic nanoparticle-metal–organic framework(plasmonicNP-MOF) hybrid nanostructures have emerged as distinctive platformsthat synergistically combine the physical, chemical, and biologicalproperties and functions of plasmonic nanoparticles and MOFs, enablingbiomedical capabilities inaccessible to either component alone. ThisPerspective focuses on a central design-to-function relationship:the structural paradigm between the plasmonic nanoparticle and theMOF governs how the properties of the two components complement oneanother and interact synergistically. We consider four principal configurations:plasmonic NPs embedded within MOF pores, plasmonic NPs decorate theMOF exterior, and a plasmonic NP serves as the core of a plasmonic@MOFcore–shell structure or forms the shell of a MOF@plasmonicNP core–shell structure. Each configuration offers distinctfunctional advantages suited to specific biomedical applications.Here, we first review the synthetic strategies and formation mechanismsunderlying these four hybrid nanostructures. We then examine how thesestructure-dependent properties manifest across three major biomedicalapplication areas: biosensing, drug delivery, and therapeutic applications.Finally, we identify the synthetic limitations constraining structuralprecision, reproducibility, and material versatility, as well as translationalbarriers that must be addressed to advance plasmonic nanoparticle–MOFhybrids toward robust and clinically relevant biomedical probes andplatforms.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"4857–4874"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Protecting-Group-Free S-Glycosylation Strategy for Complex S-Glycopeptide Synthesis","authors":"Ge Gao, Jinsheng Lai, Jiale Chen, Yutian Wang, Qingju Zhang, Qi Zhang","doi":"10.1021/jacsau.6c01193","DOIUrl":"https://doi.org/10.1021/jacsau.6c01193","url":null,"abstract":"<p>Protecting-group (PG)-free S-glycosylation offers anattractivestrategy for glycopeptide synthesis, yet practical methods for complexpeptides remain limited. Here, we report a non-photochemical S-glycosylationstrategy that directly couples unprotected glycosyl donors with unprotectedcysteine-containing peptides, enabling efficient access to β-S-glycopeptides.The method shows broad compatibility with glycosyl donors and peptidesubstrates and enables direct glycosylation of a structurally complex37-mer precursor bearing one free cysteine, four protected cysteines,and oxidation-sensitive functionalities, thereby facilitating theefficient synthesis of sublancin and diverse glycosylated analogues.In contrast to photochemical radical-based S-glycosylation, whichproduces α-S-glycopeptides and proved unsuitable for the full-lengthsubstrate, the present strategy allows efficient late-stage glycosylationof structurally complex peptides. Combined with a fragment-based nativechemical ligation approach for α-S-glycoside synthesis, thisplatform provides stereochemically defined sublancin analogues andreveals that the configuration of the S-glycosidic linkage stronglyinfluences antibacterial activity. These results establish a practicalPG-free platform for complex S-glycopeptide synthesis and glycocinstructure–activity studies.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5433–5438"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JACS AuPub Date : 2026-09-28Epub Date: 2026-07-13DOI: 10.1021/jacsau.6c00371
Sandeep Atla, Kai S. Yang, Erol C. Vatansever, Eun Jeong Cho, Xinyu Ma, Yugendar R. Alugubelli, Satyanarayana Nyalata, Lauren R. Blankenship, Kaustav Khatua, Demonta Coleman, Xuejiao Guo, Rachel M. Sammons, Dorsa Rabie, Banumathi Sankaran, Tahmina Pervin, Benjamin W. Neuman, Chia-Chuan D. Cho, Lai Hoang Son Le, Alan Pham, Nagarjun R. Mallampudi, Kevin N. Dalby, Shiqing Xu, Wenshe Ray Liu
{"title":"High-Throughput Screening Identifies Covalent Inhibitors with Unique Chemistry and Binding Modes for SARS-CoV-2 Main Protease","authors":"Sandeep Atla, Kai S. Yang, Erol C. Vatansever, Eun Jeong Cho, Xinyu Ma, Yugendar R. Alugubelli, Satyanarayana Nyalata, Lauren R. Blankenship, Kaustav Khatua, Demonta Coleman, Xuejiao Guo, Rachel M. Sammons, Dorsa Rabie, Banumathi Sankaran, Tahmina Pervin, Benjamin W. Neuman, Chia-Chuan D. Cho, Lai Hoang Son Le, Alan Pham, Nagarjun R. Mallampudi, Kevin N. Dalby, Shiqing Xu, Wenshe Ray Liu","doi":"10.1021/jacsau.6c00371","DOIUrl":"https://doi.org/10.1021/jacsau.6c00371","url":null,"abstract":"<p>Using an easily scalableSARS-CoV-2 main protease (M<sup>Pro</sup>) substrate, high-throughputscreening of ∼75,000 compoundsdrawn from diversity and fragment libraries was conducted. Based onscreening results, 40 inhibitors were confirmed with IC<sub>50</sub> values below 30 μM. Four hits were revalidated, and theirM<sup>Pro</sup> complexes were characterized by X-ray crystallography.For two inhibitors, CDI5573 and CDI8009, clear active-site electrondensity revealed covalent modification of Cys145, the enzyme’scatalytic cysteine. In both structures, His41 of the catalytic dyadreorients from its native hydrogen-bonding pose with Cys145 to engagein π-stacking with the inhibitors’ aromatic rings. Thetwo covalent adducts arise from distinct chemical mechanisms. CDI5573,which is a 3-nitro-1,2,5-oxazole derivative, reacts through nucleophilicaromatic substitution (S<sub>N</sub>Ar) to replace one of the nitrogroups by Cys145, whereas CDI8009 undergoes nucleophilic acyl substitutionto form a thioester with Cys145. Structure-guided optimization ofCDI5573 yielded new analogs, including one inhibitor with an IC<sub>50</sub> of 15 nM, placing this molecule among the most potent inhibitorsdeveloped for M<sup>Pro</sup>. These findings introduce new covalentchemotypes with diverse modes of engagement for M<sup>Pro</sup>, expandthe accessible space for this essential viral enzyme, provide leadswith the potential to complement existing COVID-19 therapeutics andmitigate viral resistance, and guide the targeting of other cysteineenzymes for drug discovery.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"4888–4896"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing G-Quadruplex Stability and Nonspecific Interactions in Living Cells Using 19F NMR","authors":"Qiong Wu, Wenwen Zheng, Chen Wang, Jiajing Zhao, Xiaoli Liu, Zhaofei Chai, Qing Liu, Jinbo Yu, Yansheng Ye, Guohua Xu, Maili Liu, Conggang Li","doi":"10.1021/jacsau.6c01086","DOIUrl":"https://doi.org/10.1021/jacsau.6c01086","url":null,"abstract":"<p>G-quadruplex (G4)structures play key physiological roles and serveas functional building blocks in DNA/RNA-based aptamer biosensors.Their function critically depends on their structural stability andnonspecific interactions in cells. However, the behavior of exogenouslydelivered G4s in living cells remains poorly understood. Here, using <sup>19</sup>F NMR, we monitored three representative G4 sequences, HT,hVEGFP, and TBA, in intact <em>Xenopus laevis</em> oocytes,HeLa cells, and derived lysates. We found that G4 structural stability,interactions, and NMR signal detectability are cell-type-dependent.In oocytes, all three G4s maintain detectable folded signals, withTBA showing slight time-dependent degradation. In HeLa cells, foldedsignals are absent for all three G4s due to intracellular interactions.HT and TBA undergo degradation in the cytoplasm rather than in thenucleus, whereas hVEGFP uniquely remains protected from degradationowing to both its higher thermal stability and protective interactions.These findings highlight the non-negligible effect of the cellularenvironment and the necessity of studying G4s in their native cellularcontext. Furthermore, we demonstrated that cell lysates can serveas a practical platform for reflecting G4 stability in intact cells.Collectively, this work deepens our understanding of G4 behavior incells and provides a basis for improvement of G4-based agents.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5410–5419"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JACS AuPub Date : 2026-09-28Epub Date: 2026-08-13DOI: 10.1021/jacsau.6c00738
Hailey Hendricks, Raina M. Morley, Angel Y. Gomez, Yokari Godínez-Loyola, Matthew V. Pecoraro, Gregory D. Scholes, Jose B. Roque
{"title":"Unlocking Distinct Excited States of a Nickel(II) Complex Without Modulating the Primary Coordination Sphere","authors":"Hailey Hendricks, Raina M. Morley, Angel Y. Gomez, Yokari Godínez-Loyola, Matthew V. Pecoraro, Gregory D. Scholes, Jose B. Roque","doi":"10.1021/jacsau.6c00738","DOIUrl":"https://doi.org/10.1021/jacsau.6c00738","url":null,"abstract":"<p>Traditional efforts in modulating the reactivity of metalcentersfocus on tuning parameters in the primary coordination sphere. Theability to embed stimuli-responsive functionality in the secondarycoordination sphere to modulate metal center reactivity representsa distinct strategy for expanding transition metal reactivity whileleaving the primary coordination sphere unmodified. Herein, we describethe incorporation of a photoresponsive unit, fluorenone, into thesecondary coordination sphere of a Ni(II) complex resulting in a significantperturbation of the complex electronic structure, manifesting in distinctexcited states that cannot be predicted by the metal complex or fluorenoneunit alone. Using the activation of strong nickel(II) trifluoromethylbonds as a readout of this strategy, the incorporation of latent ligand-centeredradicals enabled near-quantitative generation of trifluoromethyl radical.Comparisons with a control complex lacking the appended fluorenoneunit demonstrated the unique role of the appended fluorenone, showcasingthe ability to endow photoreactivity to an otherwise unreactive complex.Mechanistic studies including TD-DFT calculations, cyclic voltammetry,and transient absorption spectroscopy support that irradiation withvisible light leads to metal-to-ligand charge transfer followed byrelaxation to a long-lived <sup>3</sup>d–d state. The studiespresented herein showcase a ligand design principle focused on secondarycoordination sphere edits through the introduction of latent ligand-centeredradicals, allowing for the direct tuning of the metal center reactivity.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5068–5080"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydration Topology Manipulates CO2 Transport in Water-Saturated Micropores of Functionalized Covalent Organic Frameworks","authors":"Wanting Xie, Phornphimon Maitarad, Thanyada Rungrotmongkol, Changchun Wang, Jia Guo","doi":"10.1021/jacsau.6c01003","DOIUrl":"https://doi.org/10.1021/jacsau.6c01003","url":null,"abstract":"<p>The confinement effectof nanochannels (<2 nm) dictates thegas–liquid distribution at solid–liquid interfaces,yet the effect of interfacial chemistry on their kinetic behaviorslacks insightful understanding. Particularly, the interfacial CO<sub>2</sub> transport mechanism is critical for CO<sub>2</sub> capturein hydrated environments. Herein, we employ nonequilibrium moleculardynamics simulations combined with density functional theory calculationsto elucidate CO<sub>2</sub> transport mechanisms in fully hydratedone-dimensional micropores of covalent organic frameworks (COFs).Our results demonstrate that pore-wall chemistry regulates transportnot directly through adsorption strength alone, but by reshaping thetopology and dynamic organization of confined hydration networks.Without functionalization, the pristine COF channels form an orderedhydration structure that anchors CO<sub>2</sub> on adsorption sitesand imposes substantial across-layer transport resistance. Functionalizationof pore walls disrupts this hydration organization, accelerating CO<sub>2</sub> transport via distinct microscopic regimes and promotingspatial coexistence of CO<sub>2</sub> and water. Notably, fluorinefunctionalization establishes a mobility-dominated regime that minimizesfriction, inverting the preference from H<sub>2</sub>O-favored toCO<sub>2</sub>-favored transport and achieving a nearly 3-fold increasein axial selectivity. This work reveals that CO<sub>2</sub> transportis controlled by hydration-mediated transport energetics. These findingsoffer molecular-level perspectives for design of microporous materialsby highlighting importance of balancing interfacial affinity and transportresistance within confined hydration environments.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5317–5327"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JACS AuPub Date : 2026-09-28Epub Date: 2026-08-18DOI: 10.1021/jacsau.6c01002
Zhi Zhang, Quanli Shen, Zekang Ma, Xiaohe Miao, Zexin Jin
{"title":"Thermodynamic Locking of Conformational Chirality in a [9]Cycloparaphenylene","authors":"Zhi Zhang, Quanli Shen, Zekang Ma, Xiaohe Miao, Zexin Jin","doi":"10.1021/jacsau.6c01002","DOIUrl":"https://doi.org/10.1021/jacsau.6c01002","url":null,"abstract":"<p>Herein, we reportthe thermodynamic locking of conformationalchiralityin a [9]cycloparaphenylene (CPP) by external appending of (<em>R</em>)<em>-</em> or (<em>S</em>)<em>-</em>BINOL units. Through-space steric interactions induce asymmetrictorsion in the CPP backbone, generating a strained nanohoop with thelowest-energy conformer (Δ<em>G</em> = −2.9 kcalmol<sup>–1</sup>, corresponding to >99% population of thepreferredconformer at 293 K). Temperature- and solvent-dependent circular dichroism(CD) spectra exhibit minimal signal variation, in marked contrastto conventional dynamic chiral systems and the monomeric precursor.Variable-temperature NMR reveals rapid interconversion (Δ<em>G</em><sup>‡</sup> = 12.4 kcal mol<sup>–1</sup>), confirming fast kinetics that enable equilibration to the thermodynamicallyfavored twisted conformation. Single-crystal X-ray diffraction andtime-dependent density-functional theory (TD-DFT) calculations, includingmodel compounds devoid of BINOL chromophores, unambiguously assignthe intense Cotton effects to torsionally distorted CPP-centered π–π*transitions.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5328–5335"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JACS AuPub Date : 2026-09-28Epub Date: 2026-08-22DOI: 10.1021/jacsau.6c00425
Yongke Lei, Xiyu Luo, Lutz Ackermann, Jiayu Mo
{"title":"Cobalt-Catalyzed Halogen-Retentive C–H Activation and Its Application in Medicinal Chemistry","authors":"Yongke Lei, Xiyu Luo, Lutz Ackermann, Jiayu Mo","doi":"10.1021/jacsau.6c00425","DOIUrl":"https://doi.org/10.1021/jacsau.6c00425","url":null,"abstract":"<p>The development of C–C bond-forming strategiesthat retainthe halogen atom represents an attractive yet challenging endeavorin synthetic chemistry, offering unique opportunities for downstreamdiversification. Herein, we report the halogen-retentive C–Hannulation of haloalkynes, particularly bromoalkynes, enabled by anearth-abundant cobalt catalyst. The retained bromine atom serves asa versatile linchpin for subsequent C–H activation reactions,providing a general synthetic route for potential bioactive moleculesand identifying a new compound with <em>anti</em>-cancer activity.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"4922–4928"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comprehensive Evaluation of Oxidation Resistance for Tertiary Phosphines Using Universal Machine Learning Interatomic Potential-Aided Molecular Dynamics Simulation","authors":"Toshiya Sato, Yuri Asai, Uika Koshimizu, Yuji Hakozaki, Kenshin Takei, Kazuki Mori, Shunsaku Yasumura, Tatsushi Ikeda, Yoshihiro Yayama","doi":"10.1021/jacsau.6c00783","DOIUrl":"https://doi.org/10.1021/jacsau.6c00783","url":null,"abstract":"<p>Tertiary phosphinesplay important roles in a wide range of chemicalreactions, but they suffer from oxidation in air. Here, we proposea computational workflow for the comprehensive prediction of oxidationresistance in tertiary phosphines based on molecular dynamics (MD)simulations using Matlantis PFP, a universal machine learning interatomicpotential (uMLIP). MD simulations were conducted for 51 differenttertiary phosphines and analyzed to estimate mean survival time bysurvival analysis (τ). The resulting τ reproduced experimentallyand theoretically recognized trends in oxidation resistance acrosschemically diverse phosphines. In particular, it captured electronic,steric, and aromatic effects on oxidation resistance, even in systemswhere these factors are intertwined. Comparisons with reported oxidationbehaviors further showed that τ correctly identifies both highlyair-sensitive and highly air-stable phosphines. These results demonstratethat the present workflow provides a practical, generalizable toolfor pre-experimental assessment of phosphine oxidation resistanceand for more rational ligand design.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"6 9","pages":"5102–5117"},"PeriodicalIF":8.5,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}