2-O-α-d-glucopyranosyl-l-ascorbic acid (AA-2G) is a highly stable glycosylated derivative of vitamin C with broad applications in the food, pharmaceutical, and cosmetic industries. Sucrose phosphorylase (SPase) serves as a promising biocatalyst for the efficient synthesis of AA-2G from sucrose and L-AA. However, its industrial application is often limited by insufficient thermostability. In this study, the thermostability of SPase from Bifidobacterium longum (BlSPase) was significantly improved through an integrated computational semirational design strategy. Using PROSS, DeepDDG, and FireProt, a smart mutant library was constructed, leading to the identification of a positive mutant, G197A, with a half-life extended by 24.75 min and a melting temperature increased by 2.1 °C compared to the wild-type enzyme. Under optimized high-cell-density fermentation in a 10-L bioreactor and whole-cell catalytic conditions, G197A achieved an AA-2G titer of 383.13 g/L and a conversion rate of 80.97%. Furthermore, an anion exchange-based purification process was developed, affording high-purity AA-2G, as confirmed by HPLC and NMR analyses. This work paves the way for the industrial application of SPase by providing a robust computational framework for stability engineering, enabling sustainable and high-yield AA-2G production.
{"title":"Computational Design and Process Intensification for High-Level Production of AA-2G by a Robust Sucrose Phosphorylase","authors":"Jiajing Guo, Lukasz Peplowski, Wei Shen, Haiquan Yang, Li Zhou, Yuanyuan Xia, Xianzhong Chen","doi":"10.1021/acssuschemeng.5c12586","DOIUrl":"https://doi.org/10.1021/acssuschemeng.5c12586","url":null,"abstract":"2-<i>O</i>-α-<span>d</span>-glucopyranosyl-l-ascorbic acid (AA-2G) is a highly stable glycosylated derivative of vitamin C with broad applications in the food, pharmaceutical, and cosmetic industries. Sucrose phosphorylase (SPase) serves as a promising biocatalyst for the efficient synthesis of AA-2G from sucrose and L-AA. However, its industrial application is often limited by insufficient thermostability. In this study, the thermostability of SPase from <i>Bifidobacterium longum</i> (BlSPase) was significantly improved through an integrated computational semirational design strategy. Using PROSS, DeepDDG, and FireProt, a smart mutant library was constructed, leading to the identification of a positive mutant, G197A, with a half-life extended by 24.75 min and a melting temperature increased by 2.1 °C compared to the wild-type enzyme. Under optimized high-cell-density fermentation in a 10-L bioreactor and whole-cell catalytic conditions, G197A achieved an AA-2G titer of 383.13 g/L and a conversion rate of 80.97%. Furthermore, an anion exchange-based purification process was developed, affording high-purity AA-2G, as confirmed by HPLC and NMR analyses. This work paves the way for the industrial application of SPase by providing a robust computational framework for stability engineering, enabling sustainable and high-yield AA-2G production.","PeriodicalId":25,"journal":{"name":"ACS Sustainable Chemistry & Engineering","volume":"3 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146268","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}
Pub Date : 2026-02-10DOI: 10.1021/acs.orglett.6c00041
Chang Gao, Nana Shen, Qianting Zhou, Xinying Zhang, Xuesen Fan
Presented herein is a condition-controlled selective synthesis of isochromene fused indenone (3) or Indane fused indanone derivatives (4) via the cascade reactions of 3-phenyl[1,2,3]triazolo[1,5-a]pyridine (1) with diazo indanedione (2). The formation of products is initiated by Rh(III)-catalyzed aryl C–H alkylation of 1 with 2 followed by denitrogenation of the pyridotriazole moiety to form a Rh-carbene species as the key intermediate. When the reaction is carried out in DCM, the Rh-carbene species undergoes an intramolecular O–H bond insertion with the enol moiety followed by proto-demetalation to give product 3. When the reaction is carried out in HFIP, on the other hand, the Rh-carbene species chooses to take part in an intermolecular O–H bond insertion with HFIP, followed by an intramolecular carbonyl insertion and proto-demetalation to give product 4. To our knowledge, such a solvent-dependent selective O–H bond carbene insertion leading to the formation of distinct polycyclic compounds from the same starting materials has not been reported previously. In general, the protocols developed herein feature high efficiency, good atom/step-economy, broad substrate scope and ready scalability. Moreover, the products could be readily transformed into other valuable products.
{"title":"Selective Synthesis of Isochromene Fused Indenone or Indane Fused Indanone Derivatives Featuring with Solvent-Dependent Intra- or Intermolecular O–H Bond Carbene Insertion","authors":"Chang Gao, Nana Shen, Qianting Zhou, Xinying Zhang, Xuesen Fan","doi":"10.1021/acs.orglett.6c00041","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00041","url":null,"abstract":"Presented herein is a condition-controlled selective synthesis of isochromene fused indenone (<b>3</b>) or Indane fused indanone derivatives (<b>4</b>) via the cascade reactions of 3-phenyl[1,2,3]triazolo[1,5-<i>a</i>]pyridine (<b>1</b>) with diazo indanedione (<b>2</b>). The formation of products is initiated by Rh(III)-catalyzed aryl C–H alkylation of <b>1</b> with <b>2</b> followed by denitrogenation of the pyridotriazole moiety to form a Rh-carbene species as the key intermediate. When the reaction is carried out in DCM, the Rh-carbene species undergoes an intramolecular O–H bond insertion with the enol moiety followed by proto-demetalation to give product <b>3</b>. When the reaction is carried out in HFIP, on the other hand, the Rh-carbene species chooses to take part in an intermolecular O–H bond insertion with HFIP, followed by an intramolecular carbonyl insertion and proto-demetalation to give product <b>4</b>. To our knowledge, such a solvent-dependent selective O–H bond carbene insertion leading to the formation of distinct polycyclic compounds from the same starting materials has not been reported previously. In general, the protocols developed herein feature high efficiency, good atom/step-economy, broad substrate scope and ready scalability. Moreover, the products could be readily transformed into other valuable products.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146339","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}
Pub Date : 2026-02-10DOI: 10.1021/acs.macromol.5c03074
Ruichun Du, Jie Gao, Zekun Zhang, Deshuo Kong, Zepeng Li, Meili Song, Hongsen Zhu, Xinxin Jin, Xicheng Sun, Yi Cao, Jinglei Hu, Qiuhong Zhang, Xudong Jia
Conventional tough ionogels designed via energy-dissipative strategies (sacrificial bonds and double networks) face an inherent trade-off between mechanical robustness and recoverability. Here, we present a topological engineering approach utilizing ring-size-tuned polyrotaxanes (PRs) with γ-cyclodextrin (γ-CD) sliding rings to resolve this conflict. By steric hindrance-modulated synthesis, γ-polyrotaxane (γ-PR) with bigger size of ring cavity and lower sliding friction was integrated into a poly(acrylic acid) (PAA) ionogel. The resulting ionogels achieved high stretchability of 768%, high toughness (work of fracture) of 296 kJ m–3, and low hysteresis (residual strain ∼4.5%), surpassing most gels cross-linked by polyrotaxanes. Furthermore, single-molecule force spectroscopy and molecular dynamics simulations of α-PR and γ-PR systems revealed that the γ-cyclodextrin with a larger ring size possessed higher dynamics and lower ring-axle friction, enabling smoother sliding motion to realize better stress homogenization and minimized energy dissipation between rings and axles. Our work establishes ring-size modulation in slide-ring architectures as a paradigm-shifting strategy to overcome the toughness-recovery trade-off, advancing polyrotaxane-cross-linked gels toward commercial applications.
{"title":"Friction Modulation via Ring-Size Engineering of Polyrotaxanes for Synergistically Tough and Low-Hysteresis Ionogels","authors":"Ruichun Du, Jie Gao, Zekun Zhang, Deshuo Kong, Zepeng Li, Meili Song, Hongsen Zhu, Xinxin Jin, Xicheng Sun, Yi Cao, Jinglei Hu, Qiuhong Zhang, Xudong Jia","doi":"10.1021/acs.macromol.5c03074","DOIUrl":"https://doi.org/10.1021/acs.macromol.5c03074","url":null,"abstract":"Conventional tough ionogels designed via energy-dissipative strategies (sacrificial bonds and double networks) face an inherent trade-off between mechanical robustness and recoverability. Here, we present a topological engineering approach utilizing ring-size-tuned polyrotaxanes (PRs) with γ-cyclodextrin (γ-CD) sliding rings to resolve this conflict. By steric hindrance-modulated synthesis, γ-polyrotaxane (γ-PR) with bigger size of ring cavity and lower sliding friction was integrated into a poly(acrylic acid) (PAA) ionogel. The resulting ionogels achieved high stretchability of 768%, high toughness (work of fracture) of 296 kJ m<sup>–3</sup>, and low hysteresis (residual strain ∼4.5%), surpassing most gels cross-linked by polyrotaxanes. Furthermore, single-molecule force spectroscopy and molecular dynamics simulations of α-PR and γ-PR systems revealed that the γ-cyclodextrin with a larger ring size possessed higher dynamics and lower ring-axle friction, enabling smoother sliding motion to realize better stress homogenization and minimized energy dissipation between rings and axles. Our work establishes ring-size modulation in slide-ring architectures as a paradigm-shifting strategy to overcome the toughness-recovery trade-off, advancing polyrotaxane-cross-linked gels toward commercial applications.","PeriodicalId":51,"journal":{"name":"Macromolecules","volume":"3 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146402","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}
Pub Date : 2026-02-10DOI: 10.1021/acs.inorgchem.5c04650
Erica S. Knorr, Jordan C. Kelly, Ryan B. Gaynor, Thomas N. Rohrabaugh, Jr., Caleb A. Brown, Daniel P. Harrison
A series of six phenyl-substituted 4′-phenyl-2,2′:6′,2″-terpyridine, RPhTerpy, iridium(III) complexes of the form [Ir(RPhTerpy)(ppy)Cl](PF6), where ppy is C^N cyclometalated 2-(phenyl)pyridine, and with Hammett parameters spanning 1.69 units, were synthesized using microwave-assisted reaction procedures and characterized via physical (cyclic voltammetry, NMR, crystallography) and photophysical methods (absorption, emission, time-correlated single photon counting, Franck–Condon line shape analysis). The iridium complexes’ redox potentials, electrochemically determined ground state HOMO–LUMO gap (eHLG), photophysically determined energy gap between ground- and excited-state (E00, 77 K), estimated excited-state reduction potential (E(Ir*/–)), and time-dependent density functional theory predicted HOMO–LUMO gap and lowest energy transition (LET) correlate strongly to the ligands’ Hammett parameters, suggesting that the Hammett parameter can be used as a convenient method to model and fine-tune the physical and photophysical characteristics for this series of Ir(III) complexes. These analyses reveal similar correlations when applied to data for emissive complexes previously reported. Experimental and computational modeling data indicate that the HOMO and LUMO are effectively decoupled, suggesting independent control over both is possible and offering a general methodology for high-resolution design of desired characteristics.
{"title":"High-Resolution Tuning of Iridium(III) 4′-Aryl-terpy Chromophores: A Hammett Parameter-Guided General Methodology for Systematic Property Control through Orbital Decoupling","authors":"Erica S. Knorr, Jordan C. Kelly, Ryan B. Gaynor, Thomas N. Rohrabaugh, Jr., Caleb A. Brown, Daniel P. Harrison","doi":"10.1021/acs.inorgchem.5c04650","DOIUrl":"https://doi.org/10.1021/acs.inorgchem.5c04650","url":null,"abstract":"A series of six phenyl-substituted 4′-phenyl-2,2′:6′,2″-terpyridine, <b>RPhTerpy</b>, iridium(III) complexes of the form [Ir(<b>RPhTerpy</b>)(ppy)Cl](PF<sub>6</sub>), where ppy is C^N cyclometalated 2-(phenyl)pyridine, and with Hammett parameters spanning 1.69 units, were synthesized using microwave-assisted reaction procedures and characterized via physical (cyclic voltammetry, NMR, crystallography) and photophysical methods (absorption, emission, time-correlated single photon counting, Franck–Condon line shape analysis). The iridium complexes’ redox potentials, electrochemically determined ground state HOMO–LUMO gap (eHLG), photophysically determined energy gap between ground- and excited-state (<i>E</i><sub>00</sub>, 77 K), estimated excited-state reduction potential (<i>E</i>(Ir*<sup>/–</sup>)), and time-dependent density functional theory predicted HOMO–LUMO gap and lowest energy transition (LET) correlate strongly to the ligands’ Hammett parameters, suggesting that the Hammett parameter can be used as a convenient method to model and fine-tune the physical and photophysical characteristics for this series of Ir(III) complexes. These analyses reveal similar correlations when applied to data for emissive complexes previously reported. Experimental and computational modeling data indicate that the HOMO and LUMO are effectively decoupled, suggesting independent control over both is possible and offering a general methodology for high-resolution design of desired characteristics.","PeriodicalId":40,"journal":{"name":"Inorganic Chemistry","volume":"39 1","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146440","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}
Gaussian binning is a method for analyzing the results of classical dynamical simulations of gas-phase and gas-surface reactions that has been used since the early 2000s in order to improve predictions of state-resolved cross sections and related quantities measured in molecular beam experiments. In this method, classical trajectories are assigned Gaussian statistical weights, with much higher weights given to product energies closer to their quantized values. Here, we extend this idea to the activated complex in two ways: (i) treating it as if it were in a stationary state, just like the products, which requires as narrow a Gaussian as possible, and (ii) considering the activated complex as being in a time-dependent state, broadening the Gaussian so that the statistical properties of the activated complex are consistent with the time–energy uncertainty relation. The latter approach, which builds on a recent semiclassical study of chemical reaction thresholds [L. Bonnet, C. Crespos and M. Monnerville, J. Chem. Phys., 2022, 157, 094114], is coupled with simple calculations of tunneling through adiabatic barriers in the parabolic limit. The resulting methods are then used to calculate the reaction probability for two model processes involving, respectively, long-lived and short-lived activated complexes. The agreement with quantum probabilities appears to be very good. Based on these results, the shapes of quantum probabilities are analysed from the classical dynamics and the time–energy uncertainty relation. The question of zero-point energy violation at the transition state is examined in light of the preceding results.
高斯分形是一种分析经典气相和气表面反应动力学模拟结果的方法，自21世纪初以来一直用于改进分子束实验中状态分辨截面和相关量的预测。在该方法中，经典轨迹被赋予高斯统计权值，更接近其量子化值的积能被赋予更高的权值。在这里，我们以两种方式将这一想法扩展到活化配合物：(i)将其视为处于静止状态，就像产物一样，这需要尽可能窄的高斯分布；（ii）将活化配合物视为处于时间依赖状态，扩大高斯分布，使活化配合物的统计特性与时间-能量不确定性关系一致。后一种方法是建立在最近对化学反应阈值的半经典研究的基础上的。Bonnet， C. Crespos和M. Monnerville， J. Chem。理论物理。[j],[2022, 157, 094114]，并结合了在抛物线极限下通过绝热障的简单计算。然后用所得的方法计算两个模型过程的反应概率，分别涉及长寿命和短寿命活化复合物。与量子概率的一致性似乎非常好。在此基础上，从经典动力学和时间-能量不确定性关系分析了量子概率的形状。根据前面的结果，研究了过渡态的零点能量违逆问题。
{"title":"Combining classical reactive scattering and the time–energy uncertainty relation","authors":"Laurent Bonnet, Maurice Monnerville","doi":"10.1039/d5cp04371a","DOIUrl":"https://doi.org/10.1039/d5cp04371a","url":null,"abstract":"Gaussian binning is a method for analyzing the results of classical dynamical simulations of gas-phase and gas-surface reactions that has been used since the early 2000s in order to improve predictions of state-resolved cross sections and related quantities measured in molecular beam experiments. In this method, classical trajectories are assigned Gaussian statistical weights, with much higher weights given to product energies closer to their quantized values. Here, we extend this idea to the activated complex in two ways: (i) treating it as if it were in a stationary state, just like the products, which requires as narrow a Gaussian as possible, and (ii) considering the activated complex as being in a time-dependent state, broadening the Gaussian so that the statistical properties of the activated complex are consistent with the time–energy uncertainty relation. The latter approach, which builds on a recent semiclassical study of chemical reaction thresholds [L. Bonnet, C. Crespos and M. Monnerville, <em>J. Chem. Phys.</em>, 2022, <strong>157</strong>, 094114], is coupled with simple calculations of tunneling through adiabatic barriers in the parabolic limit. The resulting methods are then used to calculate the reaction probability for two model processes involving, respectively, long-lived and short-lived activated complexes. The agreement with quantum probabilities appears to be very good. Based on these results, the shapes of quantum probabilities are analysed from the classical dynamics and the time–energy uncertainty relation. The question of zero-point energy violation at the transition state is examined in light of the preceding results.","PeriodicalId":99,"journal":{"name":"Physical Chemistry Chemical Physics","volume":"177 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gerardo U. Juarez-Romero, Xun Sun, Juan Gerez, Christophe den Auwer, Gautier Landrot, Maarten Nachtegaal, Roland Riek, Jinghui Luo, Liliana Quintanar
Tau protein is a microtubule-associated protein central to the pathogenesis of Alzheimer’s disease (AD) and other tauopathies. While metal ion homeostasis is disrupted in AD, the presence of copper and zinc in neurofibrillary tangles suggests a pathological role for metal-tau interactions. In this study, the metal binding properties of Tau441 were probed using a wide range of spectroscopic tools. Specifically, electronic paramagnetic resonance, circular dichroism, nuclear magnetic resonance (NMR) and X-ray absorption spectroscopy (XAS) results point to a single high-affinity Cu2+ binding site within the microtubule-binding domain (MTBD), coordinated by the bis-His motif in R3 (His329/His330), possibly His299 and an oxygen-based ligand. This complex can be reduced resulting into a trigonal Cu+-Tau441 complex involving Cys322, His299 and a third ligand (likely Cys291 or His 329/330), as characterized by XAS and NMR. NMR and XAS results indicate the presence of three Zn2+ binding sites: one high-affinity site in the MTBD involving His299, His330, Cys322 and Asp295, and two lower-affinity sites in the N-terminal region, coordinated predominantly by carboxylate and His residues. Moreover, the impact of Cu2+ and Zn2+ ions on the amyloid aggregation of full length Tau441 was evaluated using thioflavin T fluorescence, electrophoresis and transmission electron microscopy. Both metal ions significantly accelerate aggregation, promoting the formation of amyloid fibrils with distinct morphologies. Our study provides valuable structural insights into the copper and zinc binding sites in Tau441 that provide a rational basis to understand the impact of metal ions in amyloid fibril aggregation and morphology. The current study expands the bioinorganic facet of AD and other tauopathies, and it underscores the importance of metal–tau interactions as potential therapeutic targets in these neurodegenerative diseases.
{"title":"Tau is a metal binding protein: Structural insights into copper and zinc coordination sites and their impact on amyloid aggregation.","authors":"Gerardo U. Juarez-Romero, Xun Sun, Juan Gerez, Christophe den Auwer, Gautier Landrot, Maarten Nachtegaal, Roland Riek, Jinghui Luo, Liliana Quintanar","doi":"10.1039/d5sc08604c","DOIUrl":"https://doi.org/10.1039/d5sc08604c","url":null,"abstract":"Tau protein is a microtubule-associated protein central to the pathogenesis of Alzheimer’s disease (AD) and other tauopathies. While metal ion homeostasis is disrupted in AD, the presence of copper and zinc in neurofibrillary tangles suggests a pathological role for metal-tau interactions. In this study, the metal binding properties of Tau441 were probed using a wide range of spectroscopic tools. Specifically, electronic paramagnetic resonance, circular dichroism, nuclear magnetic resonance (NMR) and X-ray absorption spectroscopy (XAS) results point to a single high-affinity Cu<small><sup>2+</sup></small> binding site within the microtubule-binding domain (MTBD), coordinated by the bis-His motif in R3 (His329/His330), possibly His299 and an oxygen-based ligand. This complex can be reduced resulting into a trigonal Cu<small><sup>+</sup></small>-Tau441 complex involving Cys322, His299 and a third ligand (likely Cys291 or His 329/330), as characterized by XAS and NMR. NMR and XAS results indicate the presence of three Zn<small><sup>2+</sup></small> binding sites: one high-affinity site in the MTBD involving His299, His330, Cys322 and Asp295, and two lower-affinity sites in the N-terminal region, coordinated predominantly by carboxylate and His residues. Moreover, the impact of Cu<small><sup>2+</sup></small> and Zn<small><sup>2+</sup></small> ions on the amyloid aggregation of full length Tau441 was evaluated using thioflavin T fluorescence, electrophoresis and transmission electron microscopy. Both metal ions significantly accelerate aggregation, promoting the formation of amyloid fibrils with distinct morphologies. Our study provides valuable structural insights into the copper and zinc binding sites in Tau441 that provide a rational basis to understand the impact of metal ions in amyloid fibril aggregation and morphology. The current study expands the bioinorganic facet of AD and other tauopathies, and it underscores the importance of metal–tau interactions as potential therapeutic targets in these neurodegenerative diseases.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":"133 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145975","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}
Javier Salazar, Yoan Hidalgo-Rosa, Pia C. Burboa, Cesar Pazo-Carballo, Yazmín Arellano, Camila Le-Roy, Jaime Llanos, Yi-nan Wu, Nestor Escalona, Ximena Zárate, Eduardo Schott
The administration of drugs with low solubility or absorption, such as calcium channel blockers (CCB) Amlodipine, Nifedipine, and Nimodipine, affects the recovery of complicated health conditions related to cardiovascular diseases. The development of a drug delivery device based on MOFs is a rising topic. Thus, in this work the use of MOF UiO-66 as a platform to develop a drug delivery device was analyzed using CCB drugs through an empirical and theoretical approach. Our results demonstrate that UiO-66 adsorb and release the three studied drugs without altering the chemical or physical properties of the material or the drugs. Moreover, computational studies evidence that dispersive energies are key to Nimodipine and Nifedipine interaction with the material, allowing a better understanding of the release behavior observed for each drug. Finally, the effect over the biological activity of the drugs was evaluated using Human Microvascular Endothelial cells demonstrating that the material can improve the bioavailability of each drug allowing the reduction in a 90% of the doses needed to attain a physiological effect. These results support the potential of UiO-66 as a central component in the development of a versatile drug delivery system aimed at improving the treatment of patients with cardiovascular diseases.
{"title":"A rational development of a drug delivery device based on MOF UiO-66 for calcium channel blockers drugs","authors":"Javier Salazar, Yoan Hidalgo-Rosa, Pia C. Burboa, Cesar Pazo-Carballo, Yazmín Arellano, Camila Le-Roy, Jaime Llanos, Yi-nan Wu, Nestor Escalona, Ximena Zárate, Eduardo Schott","doi":"10.1039/d5dt02037a","DOIUrl":"https://doi.org/10.1039/d5dt02037a","url":null,"abstract":"The administration of drugs with low solubility or absorption, such as calcium channel blockers (CCB) Amlodipine, Nifedipine, and Nimodipine, affects the recovery of complicated health conditions related to cardiovascular diseases. The development of a drug delivery device based on MOFs is a rising topic. Thus, in this work the use of MOF UiO-66 as a platform to develop a drug delivery device was analyzed using CCB drugs through an empirical and theoretical approach. Our results demonstrate that UiO-66 adsorb and release the three studied drugs without altering the chemical or physical properties of the material or the drugs. Moreover, computational studies evidence that dispersive energies are key to Nimodipine and Nifedipine interaction with the material, allowing a better understanding of the release behavior observed for each drug. Finally, the effect over the biological activity of the drugs was evaluated using Human Microvascular Endothelial cells demonstrating that the material can improve the bioavailability of each drug allowing the reduction in a 90% of the doses needed to attain a physiological effect. These results support the potential of UiO-66 as a central component in the development of a versatile drug delivery system aimed at improving the treatment of patients with cardiovascular diseases.","PeriodicalId":71,"journal":{"name":"Dalton Transactions","volume":"52 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amit Saha Roy, Sourav Ghosh, Indranil Nath, Sergio Caballero, Albert Escuer, Julia Mayans, Shasank Sekhar Swain
A series of penta-coordinate Cu(II) complexes were synthesised and structurally characterised to explore the relationship between coordinating environment, molecular magnetism, and antibacterial activities. A dinuclear complex, [Cu₂(L₁)₂] (1), derived from an ONNO-coordinated tetradentate ligand (H₂L₁ = N,N′-bis[(3-methoxy-2-hydroxybenzylidene)]ethane-1,2-diamine), and three paramagnetic Cu(II) complexes, [Cu₂(N₃)₂(L₂)₂] (2), [Cu(SCN)(L₂)]ₙ (3), and [Cu(CH₃COO)(L₂)]ₙ (4), stabilised by a tridentate NNO-donor ligand (HL₂ = (E)-1-(pyridin-2-yldiazenyl)naphthalen-2-ol), were isolated. Dinuclear complex 2 features an asymmetric end-on μ₁,₁-azido bridge, whereas 3 and 4 exhibit end-to-end μ₁,₃-thiocyanate/acetate bridges, forming one-dimensional polymeric architectures. Single-crystal X-ray diffraction confirmed their square-pyramidal molecular geometries. Complexes 1 and 4 exhibit field-induced single-molecule magnet (SMM) behaviour, consistent with quasi-isotropic S = ½ Cu(II) centres. All complexes show χMT ≈ 0.4 cm³•mol⁻¹•K⁻¹ with a slight decrease below 10 K. EPR parameters support the existence of mixed orbital character dz²/dx²–y² (gx = 2.23, gy = 2.06, gz = 1.90) (1) and dx²–y² (g∥ = 2.21, g⊥ = 2.06) (4) in the ground states. Molecular docking analyses demonstrated complex 3 has strong binding affinities against four biologically relevant targets: B-DNA (PDB ID: 1BNA), human DNA topoisomerase I (hTOPI, PDB ID: 1SC7), Escherichia coli MenB enzyme (EC-MenB, PDB ID: 3T88), and human serum albumin (HSA, PDB ID: 4LA0), indicating its potential for target-specific activity.
{"title":"Field-induced slow magnetic relaxation, molecular docking and antibacterial studies of quasi-isotropic copper (II) (S = ½) systems stabilised by tetradentate (ONNO) and tridentate (NNO)-donor ligands","authors":"Amit Saha Roy, Sourav Ghosh, Indranil Nath, Sergio Caballero, Albert Escuer, Julia Mayans, Shasank Sekhar Swain","doi":"10.1039/d6dt00119j","DOIUrl":"https://doi.org/10.1039/d6dt00119j","url":null,"abstract":"A series of penta-coordinate Cu(II) complexes were synthesised and structurally characterised to explore the relationship between coordinating environment, molecular magnetism, and antibacterial activities. A dinuclear complex, [Cu₂(L₁)₂] (1), derived from an ONNO-coordinated tetradentate ligand (H₂L₁ = N,N′-bis[(3-methoxy-2-hydroxybenzylidene)]ethane-1,2-diamine), and three paramagnetic Cu(II) complexes, [Cu₂(N₃)₂(L₂)₂] (2), [Cu(SCN)(L₂)]ₙ (3), and [Cu(CH₃COO)(L₂)]ₙ (4), stabilised by a tridentate NNO-donor ligand (HL₂ = (E)-1-(pyridin-2-yldiazenyl)naphthalen-2-ol), were isolated. Dinuclear complex 2 features an asymmetric end-on μ₁,₁-azido bridge, whereas 3 and 4 exhibit end-to-end μ₁,₃-thiocyanate/acetate bridges, forming one-dimensional polymeric architectures. Single-crystal X-ray diffraction confirmed their square-pyramidal molecular geometries. Complexes 1 and 4 exhibit field-induced single-molecule magnet (SMM) behaviour, consistent with quasi-isotropic S = ½ Cu(II) centres. All complexes show χMT ≈ 0.4 cm³•mol⁻¹•K⁻¹ with a slight decrease below 10 K. EPR parameters support the existence of mixed orbital character dz²/dx²–y² (gx = 2.23, gy = 2.06, gz = 1.90) (1) and dx²–y² (g∥ = 2.21, g⊥ = 2.06) (4) in the ground states. Molecular docking analyses demonstrated complex 3 has strong binding affinities against four biologically relevant targets: B-DNA (PDB ID: 1BNA), human DNA topoisomerase I (hTOPI, PDB ID: 1SC7), Escherichia coli MenB enzyme (EC-MenB, PDB ID: 3T88), and human serum albumin (HSA, PDB ID: 4LA0), indicating its potential for target-specific activity.","PeriodicalId":71,"journal":{"name":"Dalton Transactions","volume":"9 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deok-Ho Roh, Dayun Jung, James B. Gerken, Jesse J. Martinez, Eric Kazyak, Shannon S. Stahl
Direct recycling of lithium-ion battery cathodes offers considerable appeal over metallurgical approaches. Here, we demonstrate a mediated electrochemical method for direct regeneration of degraded LiFePO4 (LFP). The approach uses a redox mediator, iron propylenediamine tetraacetate, that undergoes electrochemical reduction and is circulated through an external reservoir, where it supplies the electrons needed to regenerate LFP in the presence of Li+ ions derived from LiOH oxidation. Rapid outer-sphere electron transfer is observed from the mediator to the degraded LFP material. This feature, together with good aqueous solubility of the mediator (0.3 M), supports current densities up to 100 mA/cm2, and this electrochemical recycling process is demonstrated on 100 g scale. 57Fe Mössbauer spectroscopy is used to monitor the correction of structural defects in the degraded LFP, providing the basis for regeneration of LFP that matches the electrochemical performance of pristine LFP.
{"title":"Redox-Mediated Electrochemical Regeneration of Spent LiFePO4 Battery Cathodes","authors":"Deok-Ho Roh, Dayun Jung, James B. Gerken, Jesse J. Martinez, Eric Kazyak, Shannon S. Stahl","doi":"10.1002/anie.202520213","DOIUrl":"https://doi.org/10.1002/anie.202520213","url":null,"abstract":"Direct recycling of lithium-ion battery cathodes offers considerable appeal over metallurgical approaches. Here, we demonstrate a mediated electrochemical method for direct regeneration of degraded LiFePO<sub>4</sub> (LFP). The approach uses a redox mediator, iron propylenediamine tetraacetate, that undergoes electrochemical reduction and is circulated through an external reservoir, where it supplies the electrons needed to regenerate LFP in the presence of Li<sup>+</sup> ions derived from LiOH oxidation. Rapid outer-sphere electron transfer is observed from the mediator to the degraded LFP material. This feature, together with good aqueous solubility of the mediator (0.3 M), supports current densities up to 100 mA/cm<sup>2</sup>, and this electrochemical recycling process is demonstrated on 100 g scale. <sup>57</sup>Fe Mössbauer spectroscopy is used to monitor the correction of structural defects in the degraded LFP, providing the basis for regeneration of LFP that matches the electrochemical performance of pristine LFP.","PeriodicalId":125,"journal":{"name":"Angewandte Chemie International Edition","volume":"1 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146341","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}
Pub Date : 2026-02-10DOI: 10.1021/acs.macromol.5c02209
Rithwik Ghanta, Brandon C. Jeong, Alexa S. Kuenstler, Antonia Statt
Over the past few decades, thiol-ene photopolymerization has gained popularity for synthesizing polymer networks with near-ideal architectures and predictable mechanical properties. However, growing experimental evidence of heterogeneity varying with chemical design parameters in such networks has raised questions about the chemistry’s ideality and the broader relationship between network architecture and macroscopic properties. In this work, we use a computational framework based on generalizable Kremer-Grest bead-spring representations and Monte Carlo-based reactive molecular dynamics to simulate thiol-ene-like network formation. We compare ideal step-growth thiol-ene and step-growth/chain-growth mixed-mechanism photopolymerization pathways of common thiol-based chemistries across tetra-functional cross-linker concentrations. Our results reveal the influence of synthetic variables (i.e., monomer reactivity and composition) on conversion, gelation, network architecture, and bulk mechanical properties. Additionally, we confirm these computational findings with experimental analogues, which reveal reactive accuracy through qualitative agreement between functional-group conversion and gel points. Notably, we find that network defects form more prominently at low cross-linker concentrations and with high monomer rigidity in step-growth systems, the majority of which are dangling ends. In contrast, mixed-mechanism systems produce networks less sensitive to synthetic conditions but with more heterogeneous structures, as evidenced by strand-length distributions and Voronoi volume variance. These findings underscore the role of synthetic conditions and reaction pathways in tuning network topology and provide new insights for the rational design of photopolymerization chemistries.
{"title":"The Influence of the Thiol-ene Mechanism on Polymer Network Topology","authors":"Rithwik Ghanta, Brandon C. Jeong, Alexa S. Kuenstler, Antonia Statt","doi":"10.1021/acs.macromol.5c02209","DOIUrl":"https://doi.org/10.1021/acs.macromol.5c02209","url":null,"abstract":"Over the past few decades, thiol-ene photopolymerization has gained popularity for synthesizing polymer networks with near-ideal architectures and predictable mechanical properties. However, growing experimental evidence of heterogeneity varying with chemical design parameters in such networks has raised questions about the chemistry’s ideality and the broader relationship between network architecture and macroscopic properties. In this work, we use a computational framework based on generalizable Kremer-Grest bead-spring representations and Monte Carlo-based reactive molecular dynamics to simulate thiol-ene-like network formation. We compare ideal step-growth thiol-ene and step-growth/chain-growth mixed-mechanism photopolymerization pathways of common thiol-based chemistries across tetra-functional cross-linker concentrations. Our results reveal the influence of synthetic variables (i.e., monomer reactivity and composition) on conversion, gelation, network architecture, and bulk mechanical properties. Additionally, we confirm these computational findings with experimental analogues, which reveal reactive accuracy through qualitative agreement between functional-group conversion and gel points. Notably, we find that network defects form more prominently at low cross-linker concentrations and with high monomer rigidity in step-growth systems, the majority of which are dangling ends. In contrast, mixed-mechanism systems produce networks less sensitive to synthetic conditions but with more heterogeneous structures, as evidenced by strand-length distributions and Voronoi volume variance. These findings underscore the role of synthetic conditions and reaction pathways in tuning network topology and provide new insights for the rational design of photopolymerization chemistries.","PeriodicalId":51,"journal":{"name":"Macromolecules","volume":"93 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146146401","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}
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