ACS Publications最新文献

{"title":"Macromolecular Diamidobenzimidazole Conjugates Can Activate Stimulator of Interferon Genes.","authors":"Karan Arora, Taylor L Sheehy, Jacob A Schulman, Jack R Loken, Zachary Lehmann, Blaise R Kimmel, Caitlin McAtee, Vijaya Bharti, Payton T Stone, Alissa M Weaver, Matthew Tyska, Rakesh Kumar Pathak, John T Wilson","doi":"10.1021/jacs.5c13195","DOIUrl":"https://doi.org/10.1021/jacs.5c13195","url":null,"abstract":"<p><p>A promising class of stimulator of interferon genes (STING) agonists is the non-nucleotide, small molecule, dimeric amidobenzimidazoles (diABZI), which have recently been incorporated into polymer- and antibody-drug conjugates to improve pharmacokinetics and modulate biodistribution for disease-specific applications. These approaches have leveraged diABZI variants functionalized at the 7-position of the benzimidazole for conjugation and tunable drug release from carriers. However, since this position does not interact with STING and is exposed from the binding pocket when bound in an \"open lid\" configuration, we sought to evaluate the activity of macromolecular diABZI conjugates that lack stimuli-responsive release and are instead conjugated to polymers via a stable amide linker. By synthesizing stable mPEG-diABZI conjugates and <i>N</i>,<i>N</i>-dimethylacrylamide (DMA) homopolymers from a diABZI-functionalized reversible addition-fragmentation chain-transfer (RAFT) agent, we found that these conjugates could activate STING <i>in vitro</i> with similar kinetics to highly potent diABZI analogues. Our data indicate that although diABZI-DMA conjugates enter cells via endocytosis, they can still colocalize with the ER, suggesting that intracellular trafficking processes can promote the delivery of endocytosed macromolecular diABZI compounds to STING. Furthermore, we demonstrated the <i>in vivo</i> activity of these macromolecular diABZI platforms, which inhibited tumor growth to a similar extent as small molecule variants. In conclusion, we have described new chemical strategies for the synthesis of stable macromolecular diABZI conjugates with unexpected immunostimulatory activity─findings that have potential implications for the design of polymer-diABZI conjugates and further motivate investigation of endosomal and intracellular trafficking as an alternative route for STING activation.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYCLO70: A New Challenging Pericyclic Benchmarking Set for Kinetics and Thermochemistry Evaluation.","authors":"Javier E Alfonso-Ramos, Carlo Adamo, Éric Brémond, Thijs Stuyver","doi":"10.1021/acs.jctc.5c00925","DOIUrl":"https://doi.org/10.1021/acs.jctc.5c00925","url":null,"abstract":"<p><p>Here, a new challenging benchmarking data set for cycloaddition reactions, CYCLO70, is presented and analyzed. CYCLO70 has been generated with the specific aim of being representative of the most challenging regions of the chemical reaction space surrounding Diels-Alder, dipolar cycloadditions, and (sigmatropic) rearrangement reactions with the help of an active learning approach. Testing 93 different functionals, spanning from spin-local density approximation to the most recent double-hybrid functionals, we observe that the errors on CYCLO70 are significantly bigger than those on the cycloaddition subset of BH9, the most popular benchmarking data set for this reaction class. Furthermore, we observe that the range-separated hybrid ωB97M-V is the best performing functional to model barrier heights and reaction energies, with a deviation closest to the desirable \"chemical accuracy\"; among the double hybrids, PBE-QIDH performs best, and among the fixed-range hybrids, M06-2X and r²SCAN0 emerge as the most balanced in terms of simultaneously reproducing both properties. Next, we perform a principal component analysis on the errors across the data set and demonstrate not only that the errors across different functional approximations correlate to a significant extent (the first two components explain 98% of the variance), but we also observe that functionals belonging to the same rung of Jacob's ladder cluster together in the constructed two-dimensional plot. These results were further validated on a set of Diels-Alder reactions relevant to self-healing polymer design, reinforcing the practical relevance of CYCLO70.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Nanoscale Self-Assembled Structures of Highly Hydrophobic Block Copolymers by Urea, Alkylureas, and Thiourea: Vesicle to Micelle Transition.","authors":"Nitumani Tripathi, Divya Patel, Sapana Sinha, Debes Ray, Vinod K Aswal, Debabrata Seth, Ketan Kuperkar, Pratap Bahadur","doi":"10.1021/acs.jpcb.5c05839","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c05839","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Self-assembly in poly(ethylene oxide, EO)-poly(propylene oxide, PO)-based highly hydrophobic block copolymer (BCPs) with 10%EO content (L31, L61, L81, L101, and L121) is investigated in the presence of urea, thiourea and alkyl ureas (methyl urea, dimethyl urea, and tetramethyl urea) using clouding, scattering, photophysical and computational simulation approach. This work explores BCPs with significantly lower %EO content, unreported in different areas, that highlight the novelty of our investigation. The results of our study conveyed an increase in the clouding phenomenon, the extent of which was dependent on the molecular characteristics of the BCPs. High-sensitivity differential scanning calorimetry was employed to investigate the thermodynamics of micellization. Fourier Transform Infrared spectral profile presented the involved interactions within the examined copolymeric systems. Two-dimensional nuclear Overhauser effect spectroscopy provided spatial correlation signals, confirming close molecular proximities and specific interactions in the micellar environment. Computational simulations were performed using the DFT/B3LYP method with the 3-21G basis set in Gaussian 5.0.9, and the optimized descriptors were evaluated. Interestingly, urea, thiourea, and alkyl urea, especially tetramethyl urea, significantly impacted the micellar structure, leading to demicellization in some BCPs. Here, the dimension expressed as hydrodynamic diameter (&lt;i&gt;D&lt;/i&gt;&lt;sub&gt;h&lt;/sub&gt;) and micelle size changes in the observed system were monitored using dynamic light scattering analysis with the normalized intensity autocorrelation functions providing complementary information on size-dependent scattering dynamics. Furthermore, small-angle neutron scattering studies revealed that ureas enhance the solubility of the EO segments, inducing the structural transitions from multilamellar vesicles to unilamellar vesicles to spherical or Gaussian chains, attributed to the accumulation of water molecules in the micellar proximity. The effect of varying urea concentrations on the fluorescence behavior of Nile Blue A perchlorate (NBA) dye in 1%w/v L81 vesicles at 30 °C was investigated through absorbance, fluorescence emission, excitation, and lifetime decay measurements. Here, absorbance spectra exhibited a bathochromic shift with increasing urea concentration, indicating a change in micellar polarity. The fluorescence emission also showed bathochromic shift, suggesting the migration of NBA into a more hydrophobic environment within the micellar core as urea disrupted the micelle structure. Fluorescence emission lifetime decay analysis revealed complex decay at low urea concentrations, reflecting a heterogeneous dye environment, which simplified at higher urea concentrations due to micelle collapse or dye aggregation. These findings provide insight into the role of urea in altering micelle behavior and dye aggregation, with implications for micelle-based drug delivery systems","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrophobicity-Driven and Interaction-Corrected Modeling for Gold Ion-Pair Extraction Using Ammonium and Phosphonium Ionic Liquids in 1,2-Dichloroethane.","authors":"Yusuke Tsuchida, Mahalo Gomoto, Seiya Kikuchi, Katsuhiko Tsunashima, Masahiko Matsumiya","doi":"10.1021/acs.jpcb.5c01315","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c01315","url":null,"abstract":"<p><p>Solvent extraction (SX) using 1,2-dichloroethane (DCE) solutions of ionic liquids (ILs) allows tunable hydrophobic partitioning for precious metal recovery. Bis(trifluoromethanesulfonyl)amide (TFSA)-based quaternary ammonium and phosphonium ILs (0.5-5 mM in DCE) were synthesized in this study and their Au(III) extraction from 1 M HCl (AuCl₄^-) was evaluated using atomic absorption spectroscopy (AAS) slope analysis at a 1:1 phase ratio, confirming a 1:1 ion-pair stoichiometry (slope 0.62-1.33, <i>R</i>² > 0.99) and yielding apparent extraction equilibrium constants (log<i>K</i>'_ex) of 2.6-4.9. Phosphonium ILs outperformed their ammonium analogs; alkyl and ether substituents increased log<i>K</i>'_ex via enhanced hydrophobic partitioning, whereas cyano substituents reduced log<i>K</i>'_ex due to high hydration energies, as indicated by density functional theory (DFT)-calculated solvation energy differences. COSMO-RS-predicted distribution coefficients (log<i>K</i>_d) correlated strongly with log<i>K</i>'_ex (R = 0.888, <i>R</i>² = 0.789), forming the COSMO-based optimization of metal extraction using thermodynamic parameters (COMET) model. Incorporation of the DFT-derived electron affinities into multiple regressions (MICOMET, molecular interaction-corrected COMET) improved <i>R</i>² to 0.852, quantifying the hydrophobicity (∼75%) versus interaction (∼25%) contributions to log<i>K</i>'_ex. Ultraviolet-visible (UV-Vis) spectroscopy analyses confirmed retention of AuCl₄^- speciation with the absorption maxima unchanged. This integrated framework can guide the data-driven design of IL extractants for DCE-based SX processes.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gelatin Methacryloyl Hydrogel-Coated Poly(ε-caprolactone) Microfibrous Membrane as a Friendly Blood-Contacting Material.","authors":"Yu Zhang, Xiangbo An, Ruitao Cha, Min Xiao, Pai Zhang, Ting Ma, Chunliang Zhang","doi":"10.1021/acsbiomaterials.5c01249","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c01249","url":null,"abstract":"<p><p>The electrospun microfibrous membrane (EMM), as a blood-contacting material, holds great potential that promotes vascular tissue regeneration. However, EMM suffers from quick thrombosis. Hydrogel coating offers facile preparation and customizable functionality, which can improve the antithrombosis and endothelialization of the EMM. Here, a gelatin methacryloyl<i>/N</i>, <i>N</i>-methylene bis(acrylamide) (GelMA/MBA) hydrogel-coated poly(ε-caprolactone) microfibrous membrane (GM@PCL) was prepared conveniently by electrospinning/one-step coating. The structure and stability of the GM hydrogel coating were evaluated. The effects of the GM hydrogel coating on the antithrombotic properties and endothelialization of GM@PCL were studied. The introduction of the MBA improved the stability of the GM hydrogel coating due to the formation of dual cross-linking networks. The GM hydrogel coating endowed GM@PCL with excellent hydrophilicity and improved its antithrombosis by reducing protein adsorption, platelet adhesion, and red blood cell adhesion in a rabbit arteriovenous circulation model. The abundant arginine-glycine-aspartic acid sequences in the GM hydrogel coating promoted the adhesion and growth of endothelial cells on GM@PCL, achieving a higher endothelialization rate (98.1%) than that of PCL (66.9%) within 72 h. This work presents a promising and feasible one-step coating strategy that simultaneously addresses the challenges of thrombosis and endothelialization associated with microfiber-based blood-contacting materials and cardiovascular devices.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodic Feature Characterization in Nanostructured Surfaces and Emulsions.","authors":"André Guerra, Ziheng Wang, Samuel Mathews, Alejandro D Rey, Kevin De France","doi":"10.1021/acs.langmuir.5c02320","DOIUrl":"https://doi.org/10.1021/acs.langmuir.5c02320","url":null,"abstract":"<p><p>Understanding structure-function relationships is essential to advance the manufacturing of next-generation materials with desired properties and functionalities. Precise and rapid measurement of features like wrinkle size, droplet diameter, and surface roughness is essential to establishing such structure-function relationships. To this end, this work developed feature size and surface morphology characterizations through image analysis in Python and validated them with both synthetic and experimental images. Manual measurements of biobased surfaces resulted in errors between 3.3% (<i>N</i> = 50; visually simple) and 51.2% (<i>N</i> = 100; visually complex) compared to the results of Python analysis. This analysis was also used to accurately distinguish multiple feature size populations in a given image (which were missed entirely in manual measurements) and to determine the skewness and kurtosis of biological surfaces in a surface roughness map. This work contributes to the larger goal of developing a robust and computationally cheap platform to analyze complex materials to accelerate structure-function discovery.</p>","PeriodicalId":50,"journal":{"name":"Langmuir","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In This Issue, Volume 16, Issue 9","authors":"Andrew P. Riley,&nbsp;","doi":"10.1021/acsmedchemlett.5c00497","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00497","url":null,"abstract":"","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 9","pages":"1688–1689"},"PeriodicalIF":4.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Analytic Correlation for the Thermodynamic Properties of Water at Low Temperatures (200-300 K) and High Pressures (0.1-400 MPa)\".","authors":"Julia H Grenke, Janet A W Elliott","doi":"10.1021/acs.jpcb.5c05934","DOIUrl":"https://doi.org/10.1021/acs.jpcb.5c05934","url":null,"abstract":"","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to \"Correlating Carrier Localization to Optoelectronic Behavior of Monolayer MoS₂\".","authors":"Arup Singha, Aparna Parappurath, Agniva Paul, Sanjitha K Shetty, Kenji Watanabe, Takashi Taniguchi, Arindam Ghosh, Sreemanta Mitra","doi":"10.1021/acsami.5c17397","DOIUrl":"https://doi.org/10.1021/acsami.5c17397","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oligopeptides and Polypeptides Impact Norepinephrine Detection in Lymphoid Tissue.","authors":"Sarbeshwar Ojha, Alexandra K Brooke, Blaise J Ostertag, Daniel P Murrow, Colby E Witt, Ashley E Ross","doi":"10.1021/acschemneuro.5c00554","DOIUrl":"https://doi.org/10.1021/acschemneuro.5c00554","url":null,"abstract":"<p><p>Detection of neurochemicals voltammetrically can be challenging in complex matrices like tissue. Norepinephrine (NE) is a neurotransmitter in the brain and is directly released by the sympathetic nervous system in the periphery. Fast-scan cyclic voltammetry (FSCV) is an electrochemical technique previously used to detect NE from sympathetic neurons in lymphoid tissues. Mesenteric lymph nodes present a unique challenge to FSCV due to their complex tissue matrix, which includes immune cells and neurons. These cells release various neuropeptides, cytokines, and other chemical signaling molecules, which can interfere with FSCV. Notably, Neuropeptide Y (NPY) from sympathetic neurons, and Substance P (SubP) and Calcitonin Gene-Related Peptide (CGRP) from sensory neurons are common peptides that are released locally near NE sites. These peptides are regulated by and interact with NE through complex neuronal circuits, potentially impacting FSCV NE detection. We demonstrate that increasing levels of each peptide alter voltammetric NE detection. We observed that the NE oxidation potential shifts with each peptide in vitro, and NE cyclic voltammograms exhibit unique peak broadening specific to NPY compared to SubP and CGRP, indicating that each peptide affects the carbon fiber microelectrode (CFME) differently. Overall, we show significant convolution of voltammetric NE peaks in the presence of peptides, providing evidence that future developments in materials to reduce protein fouling could significantly improve the robustness and accuracy of NE FSCV detection.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}