Journal of the American Chemical Society最新文献

De Novo Design of Proteins That Bind Naphthalenediimides, Powerful Photooxidants with Tunable Photophysical Properties

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c18151

Samuel I. Mann, Zhi Lin, Sophia K. Tan, Jiaqi Zhu, Zachary X. W. Widel, Ian Bakanas, Jarrett P. Mansergh, Rui Liu, Mark J. S. Kelly, Yibing Wu, James A. Wells, Michael J. Therien, William F. DeGrado

{"title":"De Novo Design of Proteins That Bind Naphthalenediimides, Powerful Photooxidants with Tunable Photophysical Properties","authors":"Samuel I. Mann, Zhi Lin, Sophia K. Tan, Jiaqi Zhu, Zachary X. W. Widel, Ian Bakanas, Jarrett P. Mansergh, Rui Liu, Mark J. S. Kelly, Yibing Wu, James A. Wells, Michael J. Therien, William F. DeGrado","doi":"10.1021/jacs.4c18151","DOIUrl":"https://doi.org/10.1021/jacs.4c18151","url":null,"abstract":"De novo protein design provides a framework to test our understanding of protein function and build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidants and the evaluation of the use of these proteins to generate diffusible small-molecule reactive species. Because excited-state dynamics are influenced by the dynamics and hydration of a photooxidant’s environment, it was important to not only design a binding site but also to evaluate its dynamic properties. Thus, we used computational design in conjunction with molecular dynamics (MD) simulations to design a protein, designated NBP (NDI Binding Protein), that held a naphthalenediimide (NDI), a powerful photooxidant, in a programmable molecular environment. Solution NMR confirmed the structure of the complex. We evaluated two NDI cofactors in this de novo protein using ultrafast pump–probe spectroscopy to evaluate light-triggered intra- and intermolecular electron transfer function. Moreover, we demonstrated the utility of this platform to activate multiple molecular probes for protein labeling.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"2 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462717","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}

引用次数: 0

Verdazyl-Based Radicals for High-Field Dynamic Nuclear Polarization NMR

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c13374

Jakob A. Meckes, Zachary W. Schroeder, Diganta Sarkar, Riley W. Hooper, Clara E. Faraday-Smith, Alex Brown, Rik R. Tykwinski, Vladimir K. Michaelis

{"title":"Verdazyl-Based Radicals for High-Field Dynamic Nuclear Polarization NMR","authors":"Jakob A. Meckes, Zachary W. Schroeder, Diganta Sarkar, Riley W. Hooper, Clara E. Faraday-Smith, Alex Brown, Rik R. Tykwinski, Vladimir K. Michaelis","doi":"10.1021/jacs.4c13374","DOIUrl":"https://doi.org/10.1021/jacs.4c13374","url":null,"abstract":"High-field dynamic nuclear polarization nuclear magnetic resonance (DNP NMR) spectroscopy transfers polarization from unpaired electrons in polarizing agents to nuclei of interest to boost NMR sensitivity. Verdazyl biradicals are a promising choice as polarizing agents because they have been found to generate narrower electron paramagnetic resonance (EPR) signals compared to nitroxide biradicals; an advantageous characteristic for high-field DNP when operating above 400 MHz/263 GHz. The use of verdazyl radicals as DNP polarizing agents has been very limited to date, yet, recent numerical simulations have predicted that verdazyl-nitroxide hybrid biradicals could be more effective polarizing agents than nitroxide-nitroxide biradicals. Herein, the syntheses of a series of verdazyl mono- and biradicals, as well as verdazyl-nitroxide biradicals are described. These radicals were examined in high-field DNP NMR experiments (600 MHz/395 GHz), by measuring 1H signal enhancements directly and through 13C{1H} cross-polarization experiments. X-band EPR, 1H DNP field profiles, and experiments to determine the nuclear build-up times were performed for verdazyl-nitroxide biradicals VerTEMPol and VerTEKol. These hybrid biradicals provide enhancements of up to 100-fold increased signal intensities (i.e., representing >104-fold time savings), approximately four times higher than that of the nitroxide biradical TEKPol, a commonly used polarizing agent in the field.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"34 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462715","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}

引用次数: 0

Designing Target-specific Data Sets for Regioselectivity Predictions on Complex Substrates

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c15902

Jules Schleinitz, Alba Carretero-Cerdán, Anjali Gurajapu, Yonatan Harnik, Gina Lee, Amitesh Pandey, Anat Milo, Sarah E. Reisman

{"title":"Designing Target-specific Data Sets for Regioselectivity Predictions on Complex Substrates","authors":"Jules Schleinitz, Alba Carretero-Cerdán, Anjali Gurajapu, Yonatan Harnik, Gina Lee, Amitesh Pandey, Anat Milo, Sarah E. Reisman","doi":"10.1021/jacs.4c15902","DOIUrl":"https://doi.org/10.1021/jacs.4c15902","url":null,"abstract":"The development of machine learning models to predict the regioselectivity of C(sp3)–H functionalization reactions is reported. A data set for dioxirane oxidations was curated from the literature and used to generate a model to predict the regioselectivity of C–H oxidation. To assess whether smaller, intentionally designed data sets could provide accuracy on complex targets, a series of acquisition functions were developed to select the most informative molecules for the specific target. Active learning-based acquisition functions that leverage predicted reactivity and model uncertainty were found to outperform those based on molecular and site similarity alone. The use of acquisition functions for data set elaboration significantly reduced the number of data points needed to perform accurate prediction, and it was found that smaller, machine-designed data sets can give accurate predictions when larger, randomly selected data sets fail. Finally, the workflow was experimentally validated on five complex substrates and shown to be applicable to predicting the regioselectivity of arene C–H radical borylation. These studies provide a quantitative alternative to the intuitive extrapolation from “model substrates” that is frequently used to estimate reactivity on complex molecules.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"14 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462777","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}

引用次数: 0

Rapid Microwave-Assisted Chemical Recycling of Poly(p-Phenylene Terephthalamide)

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c17791

Joël Benninga, Bert Gebben, Rudy Folkersma, Vincent S. D. Voet, Katja Loos

引用次数: 0

Fast and Massive Production of Aramid Nanofibers via Molecule Intercalation

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-21 DOI: 10.1021/jacs.4c18620

Zi-Meng Han, YuanZhen Hou, Hao-Cheng Liu, Qing-Fang Guan, Huai-Bin Yang, Kun-Peng Yang, Chong-Han Yin, Zhang-Chi Ling, Yu-Xiang Zhao, Jun Xia, YinBo Zhu, HengAn Wu, Kody Whishant, Nicholas A. Kotov, Shu-Hong Yu

{"title":"Fast and Massive Production of Aramid Nanofibers via Molecule Intercalation","authors":"Zi-Meng Han, YuanZhen Hou, Hao-Cheng Liu, Qing-Fang Guan, Huai-Bin Yang, Kun-Peng Yang, Chong-Han Yin, Zhang-Chi Ling, Yu-Xiang Zhao, Jun Xia, YinBo Zhu, HengAn Wu, Kody Whishant, Nicholas A. Kotov, Shu-Hong Yu","doi":"10.1021/jacs.4c18620","DOIUrl":"https://doi.org/10.1021/jacs.4c18620","url":null,"abstract":"Para-aramid nanofibers, one of the newest high-performance building blocks at the nanoscale, have attracted great attention due to their hard-to-find property sets and ability to form high-porosity solids. However, there are great difficulties in their scalable and sustainable production because the strong intermolecular hydrogen bonds and other interactions of aramid macromolecules lead to lengthy processes with highly corrosive solvents. Taking advantage of uniquely efficient delamination of polymer nanocrystallites, here we show that the preparation time of para-aramid nanofibers can be reduced by 2520 times (from 1 week to four min), while their concentration can be increased by 10 times. Through this molecule intercalation-induced method, novel ribbon-like aramid nanofibers are prepared. The multiscale modeling indicated that delamination of nanofibers occurs via intercalation of alcohols at nanoscale interfaces. 1000 kg nanofiber dispersions were successfully prepared within half an hour in a pilot-scale test. These findings demonstrate the realism of effective aramid recycling into a wide range of multifunctional nanofiber composites.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"127 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462718","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}

引用次数: 0

Triggered Inversion of Dual Responsive Diblock Copolypeptide Vesicles.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17033

Casey A Morrison, Ethan P Chan, Timothy J Deming

{"title":"Triggered Inversion of Dual Responsive Diblock Copolypeptide Vesicles.","authors":"Casey A Morrison, Ethan P Chan, Timothy J Deming","doi":"10.1021/jacs.4c17033","DOIUrl":"https://doi.org/10.1021/jacs.4c17033","url":null,"abstract":"We report the synthesis of amphiphilic poly(l-methionine sulfoxide)x-b-poly(dehydroalanine)y, diblock copolypeptides, MOxADHy, and their self-assembly into submicrometer-diameter unilamellar vesicles in aqueous media. The formation of vesicles was observed over an unprecedented range of copolypeptide compositions due to the unique properties and chain conformations of ADH hydrophobic segments. These copolypeptides incorporate two distinct thiol reactive components where each segment can respond differently to a single thiol stimulus. Incubation of MO35ADH30 vesicles with glutathione under intracellular mimetic conditions resulted in vesicle disruption and release of cargo. Further, incubation of MO35ADH30 vesicles with thiolglycolic acid resulted in a reversal of amphipilicity and successful in situ inversion of the vesicle assemblies. This conversion of biomimetic polymer vesicles into stable inverted vesicles using a biologically relevant stimulus at physiological pH and temperature is unprecedented. These results provide insights toward the development of advanced functional synthetic assemblies with potential uses in biology and medicine.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456264","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}

引用次数: 0

Non-van-der-Waals Oriented Two-Dimensional UiO-66 Films by Rapid Aqueous Synthesis at Room Temperature

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c11134

Heng-Yu Chi, Shuqing Song, Kangning Zhao, Kuang-Jung Hsu, Qi Liu, Yueqing Shen, Anne Faustine Sido Belin, Arthur Allaire, Ranadip Goswami, Wendy L. Queen, Kumar Varoon Agrawal

{"title":"Non-van-der-Waals Oriented Two-Dimensional UiO-66 Films by Rapid Aqueous Synthesis at Room Temperature","authors":"Heng-Yu Chi, Shuqing Song, Kangning Zhao, Kuang-Jung Hsu, Qi Liu, Yueqing Shen, Anne Faustine Sido Belin, Arthur Allaire, Ranadip Goswami, Wendy L. Queen, Kumar Varoon Agrawal","doi":"10.1021/jacs.4c11134","DOIUrl":"https://doi.org/10.1021/jacs.4c11134","url":null,"abstract":"The synthesis of MOFs in a two-dimensional (2D) film morphology is attractive for several applications including molecular and ionic separation. However, 2D MOFs have only been reported from structures that crystallize in lamellar morphology, where layers are held together by van der Waals (vdW) interaction. By comparison, UiO-66, one of the most studied MOFs because of its exceptional chemical stability, has only been reported in three-dimensional (3D) morphology. 2D UiO-66 is challenging to obtain given the robust isotropic bonds in its cubic crystal structure. Herein, we report the first synthesis of non-vdW 2D UiO-66-NH2 by developing crystal growth conditions that promote in-plane growth over out-of-plane growth. Continuous, oriented UiO-66-NH2 film with thickness tunable in the range of 0.5 to 2 unit cells could be obtained by sustainable, scalable chemistry, which yielded attractive ion–ion selectivity. The preparation of non-vdW 2D MOF is highly attractive to advance the field of MOF films for diverse applications.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"52 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462719","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}

引用次数: 0

Temperature-Dependent Mixed Valency in the Hexagonal Perovskite Cs₃NaFe₂Cl₉.

IF 14.4 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17019

David Liu, Alexander Milder, Jeremiah Stevens, Cierra Foster, Brendan Beck, Maxim Avdeev, Patrick M Woodward

{"title":"Temperature-Dependent Mixed Valency in the Hexagonal Perovskite Cs3NaFe2Cl9.","authors":"David Liu, Alexander Milder, Jeremiah Stevens, Cierra Foster, Brendan Beck, Maxim Avdeev, Patrick M Woodward","doi":"10.1021/jacs.4c17019","DOIUrl":"https://doi.org/10.1021/jacs.4c17019","url":null,"abstract":"The hexagonal perovskites Cs3NaFe2Cl9 and Cs3NaMnFeCl9 have been synthesized and investigated. Both compounds adopt the 6H perovskite structure with P63/mmc symmetry. This structure consists of dimers of face-sharing octahedra arranged on the vertices of a triangular network. The transition metal ions occupy sites in these octahedra, leading to Fe2Cl94- and FeMnCl94- bioctahedra, respectively. The bioctahedral clusters are sandwiched by layers of corner-sharing octahedra occupied by Na+ cations. Diffuse reflectance spectroscopy reveals optical transitions that arise from metal-to-metal charge transfer (Cs3NaMnFeCl9) and intervalence charge transfer (Cs3NaFe2Cl9) excitations. In Cs3NaFe2Cl9, magnetic susceptibility measurements reveal local ferromagnetic coupling (θCW = 16.7 K), mediated by the rapid exchange of an electron between the iron sites within each dimer. In contrast, the magnetic coupling between Fe3+ and Mn2+ in Cs3NaMnFeCl9 is antiferromagnetic (θCW = -41.4 K). At 100 K, the Mössbauer spectrum is dominated by a single type of iron that corresponds to Fe2.5+, signaling electron exchange between iron sites that is faster than the Mössbauer time scale (∼100 ns). Upon further cooling, the Fe2.5+ signal gives way to a 1:1 ratio of Fe2+ and Fe3+, as the thermally activated hopping slows down.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":14.4,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456262","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}

引用次数: 0

Hierarchical Reaction Logic Enables Computational Design of Complex Peptide Syntheses

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c17057

Karol Molga, Wiktor Beker, Rafał Roszak, Andrzej Czerwiński, Bartosz A. Grzybowski

{"title":"Hierarchical Reaction Logic Enables Computational Design of Complex Peptide Syntheses","authors":"Karol Molga, Wiktor Beker, Rafał Roszak, Andrzej Czerwiński, Bartosz A. Grzybowski","doi":"10.1021/jacs.4c17057","DOIUrl":"https://doi.org/10.1021/jacs.4c17057","url":null,"abstract":"The prevalent assumption in computer-assisted synthesis planning has been to rely on the wealth of reaction data and on the consideration of this vast knowledge base at every stage of route planning. Yet even if equipped with all requisite knowledge of individual reaction transforms and state-of-the-art search algorithms, the existing programs struggle when confronted with advanced targets, such as the complex peptides this work considers. By contrast, when the searches are constrained by hierarchical logic, dictating which subsets of reactions to apply at different stages of synthesis planning, these algorithms are able to plan, within minutes, complete routes to clinically relevant targets as complex as vancomycin and as large as semaglutide. Despite not being trained on any literature precedents, the routes designed by the algorithm mimic the strategies used by human experts. The hierarchical planning we describe incorporates protecting-group strategies and realistic pathway pricing and can be performed in solid-state or solution modes, in the latter case using either C-to-N or N-to-C peptide extension strategies.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"2 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462778","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}

引用次数: 0

Intracellular Photocatalytic NADH/NAD(P)H Oxidation for Cancer Drug Development

IF 15 1区化学

Journal of the American Chemical Society Pub Date : 2025-02-20 DOI: 10.1021/jacs.4c18328

Ashish Kumar Yadav, Rajesh Kushwaha, Arif Ali Mandal, Apurba Mandal, Samya Banerjee

{"title":"Intracellular Photocatalytic NADH/NAD(P)H Oxidation for Cancer Drug Development","authors":"Ashish Kumar Yadav, Rajesh Kushwaha, Arif Ali Mandal, Apurba Mandal, Samya Banerjee","doi":"10.1021/jacs.4c18328","DOIUrl":"https://doi.org/10.1021/jacs.4c18328","url":null,"abstract":"Photocatalytic cancer therapy (PCT) has emerged as a cutting-edge anticancer mechanism of action, harnessing light energy to mediate the catalytic oxidation of intracellular substrates. PCT is of significant current importance due to its potential to address the limitations of conventional chemotherapy, particularly drug resistance and side effects. This approach offers a noninvasive, targeted cancer treatment option by utilizing metal-based photocatalysts to induce redox and metabolic disorders within cancer cells. The photocatalysts disrupt the cancer cell metabolism by converting NADH/NAD(P)H to NAD+/NAD(P)+ via catalytic photoredox processes, altering intracellular NAD+/NADH or NAD(P)+/NAD(P)H ratios, which are crucial for cellular metabolism. Ir(III), Ru(II), Re(I), and Os(II) photocatalysts demonstrated promising PCT efficacy. Despite these developments, gaps remain in the literature for translating this new anticancer mechanism into clinical trials. This Perspective critically examines the developments in this research area and provides future directions for designing efficient photocatalysts for PCT.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"31 1","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462781","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}

引用次数: 0