In biological systems, nitric oxide (NO) is a crucial signaling molecule that regulates a wide range of physiological and pathological processes. Given the significance of NO, there has been considerable interest in delivering NO exogenously, particularly through light as a non-invasive therapeutic approach. However, due to the high reactivity and instability of NO under physiological conditions, directly delivering NO to targeted sites remains challenging. In recent decades, photo-responsive transition metal–nitrosyl complexes, especially based on first-row transition metals such as Mn, Fe, and Co, have emerged as efficient NO donors, offering higher delivery efficiency and quantum yields than heavy metal–nitrosyl complexes under light exposure. This review provides a comprehensive overview of current knowledge and recent developments in the field of photolabile first-row transition metal–nitrosyl complexes, focusing on the structural and electronic properties, photoreactivity, photodissociation mechanisms, and potential therapeutic applications. By consolidating the key features of photoactive nitrosyl complexes, the review offers deeper insights and highlights the potential of first-row transition metal–nitrosyl complexes as versatile tools for photo-triggered NO delivery.
在生物系统中，一氧化氮（NO）是一种重要的信号分子，可调节各种生理和病理过程。鉴于一氧化氮的重要性，人们对外源性输送一氧化氮产生了浓厚的兴趣，特别是通过光作为一种非侵入性治疗方法。然而，由于 NO 在生理条件下的高反应性和不稳定性，将 NO 直接输送到目标部位仍然具有挑战性。近几十年来，光响应过渡金属亚硝基复合物，尤其是基于第一排过渡金属（如锰、铁和钴）的过渡金属亚硝基复合物，已成为高效的 NO 给体，在光照射下比重金属亚硝基复合物具有更高的输送效率和量子产率。这篇综述全面概述了可发光的第一排过渡金属-亚硝基配合物领域的现有知识和最新进展，重点关注其结构和电子特性、光活性、光解离机制以及潜在的治疗应用。通过整合光活性亚硝基配合物的关键特征，该综述提供了更深入的见解，并突出了第一排过渡金属-亚硝基配合物作为光触发 NO 释放的多功能工具的潜力。
{"title":"Photo-triggered NO release of nitrosyl complexes bearing first-row transition metals and therapeutic applications","authors":"Seungwon Sun, Jisu Choe, Jaeheung Cho","doi":"10.1039/d4sc06820c","DOIUrl":"https://doi.org/10.1039/d4sc06820c","url":null,"abstract":"In biological systems, nitric oxide (NO) is a crucial signaling molecule that regulates a wide range of physiological and pathological processes. Given the significance of NO, there has been considerable interest in delivering NO exogenously, particularly through light as a non-invasive therapeutic approach. However, due to the high reactivity and instability of NO under physiological conditions, directly delivering NO to targeted sites remains challenging. In recent decades, photo-responsive transition metal–nitrosyl complexes, especially based on first-row transition metals such as Mn, Fe, and Co, have emerged as efficient NO donors, offering higher delivery efficiency and quantum yields than heavy metal–nitrosyl complexes under light exposure. This review provides a comprehensive overview of current knowledge and recent developments in the field of photolabile first-row transition metal–nitrosyl complexes, focusing on the structural and electronic properties, photoreactivity, photodissociation mechanisms, and potential therapeutic applications. By consolidating the key features of photoactive nitrosyl complexes, the review offers deeper insights and highlights the potential of first-row transition metal–nitrosyl complexes as versatile tools for photo-triggered NO delivery.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589164","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}
Hao-Ting Qu, Iida Partanen, Kai-Hsin Chang, Yan-Ding Lin, Igor O Koshevoy, Andrey Belyaev, Pi-Tai Chou
By strategic design and synthesis of a new series of phosphonium salts (compounds 1–7[OTf]), where [OTf]- stands for the trifluoromethanesulfonate anion, we performed comprehensive spectroscopic and dynamic studies on the photoinduced anion migration in toluene. Our aim is to probe if the anion migration is associated with an intrinsic barrier or is barrier free. After the occurrence of excited-state intramolecular charge transfer (ESICT) in 1–7, the charge redistribution of the cation triggers the translocation of the counter anion [OTf]–, resulting in emission spectral temporal evolution. As a result, we describe the photoinduced anion migration by introducing spectral response function C(t), a concept adopted from the solvent diffusional relaxation. The experimental results indicate that the anion migration lacks intrinsic barrier, i.e., the relaxation dynamics can be described by a biased Brownian motion along the charge transfer direction. The experimental findings are also qualitatively supported by theoretical calculations including restrained electrostatic potential (RESP) and hole-electron distribution analyses.
{"title":"Insights into the photoinduced anion translocation of the Donor-π-Acceptor+(ion)- molecules","authors":"Hao-Ting Qu, Iida Partanen, Kai-Hsin Chang, Yan-Ding Lin, Igor O Koshevoy, Andrey Belyaev, Pi-Tai Chou","doi":"10.1039/d4sc04738a","DOIUrl":"https://doi.org/10.1039/d4sc04738a","url":null,"abstract":"By strategic design and synthesis of a new series of phosphonium salts (compounds 1–7[OTf]), where [OTf]- stands for the trifluoromethanesulfonate anion, we performed comprehensive spectroscopic and dynamic studies on the photoinduced anion migration in toluene. Our aim is to probe if the anion migration is associated with an intrinsic barrier or is barrier free. After the occurrence of excited-state intramolecular charge transfer (ESICT) in 1–7, the charge redistribution of the cation triggers the translocation of the counter anion [OTf]–, resulting in emission spectral temporal evolution. As a result, we describe the photoinduced anion migration by introducing spectral response function C(t), a concept adopted from the solvent diffusional relaxation. The experimental results indicate that the anion migration lacks intrinsic barrier, i.e., the relaxation dynamics can be described by a biased Brownian motion along the charge transfer direction. The experimental findings are also qualitatively supported by theoretical calculations including restrained electrostatic potential (RESP) and hole-electron distribution analyses.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589174","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}
The stability of metal-organic frameworks (MOFs) in the presence of water is crucial for a wide range of applications, including the production of freshwater, desiccation, humidity control, heat pumps/chillers and capture and separation of gas. In particular, their stability under steam flow is essential since most industrial streams contain water vapor. Nevertheless, to the best of our knowledge, the stability under steam flow of Zr-based MOFs, which are among the most widely studied MOFs, has not been investigated so far. We explore it herein for three UiO-like Zr-based MOFs built from the same Zr cluster but distinct organic linkers at temperature ranging from 80 to 200 °C. We demonstrate the possibility to acquire their 91Zr NMR spectra using high magnetic field (18.8 T) and low temperature (140 K) and to interpret them by comparing experimental data with NMR parameters calculated by DFT. NMR observation of this challenging isotope combined with more conventional techniques, such as N2 adsorption, X-ray diffraction, IR, 1H and 13C solid-state NMR spectroscopies, provides information on the possible collapse of the MOF framework but also on the adsorption of molecules into the pores. We notably show that UiO-66(Zr) and UiO-66-Fum(Zr) built from terephthalate and fumarate linkers, respectively, are stable over 24 h (and even over 7 days for UiO-66(Zr)) under steam flow at all investigated temperatures, whereas UiO-67-NH2 containing 2-amino-[1,1’-biphenyl]-4,4’-dicarboxylate linker degrades under steam flow at temperature ranging from 80 to 150 °C but is preserved at 200 °C. The lower stability of UiO-67-NH2 stems from its larger pores and its weaker Zr−O coordination bonds, whereas its preservation at 200 °C results from a more limited condensation of water in the pores.
{"title":"Probing water adsorption and stability under steam flow of Zr-based metal-organic frameworks using 91Zr solid-state NMR spectroscopy","authors":"Athulya Nadol, Florian Venel, Raynald Giovine, Maeva Leloire, Christophe Volkringer, Thierry Loiseau, Christel Gervais, Caroline Mellot-Draznieks, Bertrand Doumert, Julien Trébosc, Olivier Lafon, Frédérique Pourpoint","doi":"10.1039/d4sc04589k","DOIUrl":"https://doi.org/10.1039/d4sc04589k","url":null,"abstract":"The stability of metal-organic frameworks (MOFs) in the presence of water is crucial for a wide range of applications, including the production of freshwater, desiccation, humidity control, heat pumps/chillers and capture and separation of gas. In particular, their stability under steam flow is essential since most industrial streams contain water vapor. Nevertheless, to the best of our knowledge, the stability under steam flow of Zr-based MOFs, which are among the most widely studied MOFs, has not been investigated so far. We explore it herein for three UiO-like Zr-based MOFs built from the same Zr cluster but distinct organic linkers at temperature ranging from 80 to 200 °C. We demonstrate the possibility to acquire their 91Zr NMR spectra using high magnetic field (18.8 T) and low temperature (140 K) and to interpret them by comparing experimental data with NMR parameters calculated by DFT. NMR observation of this challenging isotope combined with more conventional techniques, such as N2 adsorption, X-ray diffraction, IR, 1H and 13C solid-state NMR spectroscopies, provides information on the possible collapse of the MOF framework but also on the adsorption of molecules into the pores. We notably show that UiO-66(Zr) and UiO-66-Fum(Zr) built from terephthalate and fumarate linkers, respectively, are stable over 24 h (and even over 7 days for UiO-66(Zr)) under steam flow at all investigated temperatures, whereas UiO-67-NH2 containing 2-amino-[1,1’-biphenyl]-4,4’-dicarboxylate linker degrades under steam flow at temperature ranging from 80 to 150 °C but is preserved at 200 °C. The lower stability of UiO-67-NH2 stems from its larger pores and its weaker Zr−O coordination bonds, whereas its preservation at 200 °C results from a more limited condensation of water in the pores.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594196","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}
Sterically-hindered diarylethenes with intrinsic chirality have shown great potential in chiral signal regulation, light-controlled liquid crystals (LCs), etc. Their unique enantiospecific phototransformation between axial chirality of ring-open isomer and central chirality of ring-closed isomer can break through the bottleneck of the interference between multiple chiral centers in traditional chiral diarylethenes. However, these intrinsic chiral diarylethenes require necessary chiral resolution through preparative chiral HPLC, typically resulting in limited separation efficiency and production scale. Here, we present an enantioselective olefination strategy to directly construct intrinsic chiral diarylethenes from a prochiral sterically-hindered diarylethene, achieving high yields and enantioselectivity. The resulting isomers can be further decorated by incorporating mesogenic units, and the derivatives enable the successful reversible photoregulation of blue, green, and red reflection colors of LC with excellent thermal stability, fatigue resistance, and little texture disorderliness, demonstrating the practical application potential of direct enantioselective olefination in photoregulation with intrinsic chiral diarylethenes.
{"title":"Pd(II)-Catalyzed Enantioselective C-H Olefination and Photoregulation of Sterically-Hindered Diarylethenes","authors":"Guanlun Zhang, Xu Wu, Shiyu Mao, Mengqi Li, Honglong Hu, Bing-Feng Shi, Weihong Zhu","doi":"10.1039/d4sc05375c","DOIUrl":"https://doi.org/10.1039/d4sc05375c","url":null,"abstract":"Sterically-hindered diarylethenes with intrinsic chirality have shown great potential in chiral signal regulation, light-controlled liquid crystals (LCs), etc. Their unique enantiospecific phototransformation between axial chirality of ring-open isomer and central chirality of ring-closed isomer can break through the bottleneck of the interference between multiple chiral centers in traditional chiral diarylethenes. However, these intrinsic chiral diarylethenes require necessary chiral resolution through preparative chiral HPLC, typically resulting in limited separation efficiency and production scale. Here, we present an enantioselective olefination strategy to directly construct intrinsic chiral diarylethenes from a prochiral sterically-hindered diarylethene, achieving high yields and enantioselectivity. The resulting isomers can be further decorated by incorporating mesogenic units, and the derivatives enable the successful reversible photoregulation of blue, green, and red reflection colors of LC with excellent thermal stability, fatigue resistance, and little texture disorderliness, demonstrating the practical application potential of direct enantioselective olefination in photoregulation with intrinsic chiral diarylethenes.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589163","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}
Al oxo-hydroxide clusters, synthesized through the hydrolysis of Al³⁺ solutions, are expected to bridge the gap between metal-aqua complexes and bulk metal oxides/hydroxides. These clusters exhibit remarkable diversity in structure and composition, controlled by modulating the basicity of the solution and use of capping ligands. While anionic metal-oxo clusters, such as polyoxometalates, have been extensively studied since the early 20th century, cationic metal-oxo clusters, including those of aluminum, have gained interest more recently due to their high reactivity and potential for various applications. We explore their molecular structures and assembly into various forms, including ionic crystals, amorphous solids, and hybrid materials, for applications such as adsorption, coprecipitation, and catalysis. Furthermore, we present future perspectives, emphasizing molecular design, scalable synthetic methods, and expanded functional applications, particularly in energy and environmental sciences, where these clusters are expected to demonstrate significant potential.
{"title":"Cationic Al oxo-hydroxide clusters: syntheses, molecular structures, and functional applications","authors":"Naoki Ogiwara, Wei Zhou, Sayaka Uchida","doi":"10.1039/d4sc05707d","DOIUrl":"https://doi.org/10.1039/d4sc05707d","url":null,"abstract":"Al oxo-hydroxide clusters, synthesized through the hydrolysis of Al³⁺ solutions, are expected to bridge the gap between metal-aqua complexes and bulk metal oxides/hydroxides. These clusters exhibit remarkable diversity in structure and composition, controlled by modulating the basicity of the solution and use of capping ligands. While anionic metal-oxo clusters, such as polyoxometalates, have been extensively studied since the early 20th century, cationic metal-oxo clusters, including those of aluminum, have gained interest more recently due to their high reactivity and potential for various applications. We explore their molecular structures and assembly into various forms, including ionic crystals, amorphous solids, and hybrid materials, for applications such as adsorption, coprecipitation, and catalysis. Furthermore, we present future perspectives, emphasizing molecular design, scalable synthetic methods, and expanded functional applications, particularly in energy and environmental sciences, where these clusters are expected to demonstrate significant potential.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589160","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}
Xinyi Wen, Huishan Li, Zhijie Ju, Renren Deng, David Parker
A series of new ligands has been prepared that incorporate electron-poor aromatic moieties (dpqMe2 and dpqPh2 chromophores) into tetraazacyclododecane or triazacyclononane based complex structures, and the time-dependent photophysical properties of their Eu(III) and Tb (III) complexes evaluated for the selective and rapid ratiometric analysis of urate in diluted serum solution, together with detailed mechanistic studies probing the nature of the intermediate exciplex and the excited state dynamics using transient absorption spectroscopy.
{"title":"Mechanism of Action and Evaluation of Ratiometric Probes for Uric Acid Using Lanthanide Complexes with Tetraazatriphenylene Sensitisers","authors":"Xinyi Wen, Huishan Li, Zhijie Ju, Renren Deng, David Parker","doi":"10.1039/d4sc05743k","DOIUrl":"https://doi.org/10.1039/d4sc05743k","url":null,"abstract":"A series of new ligands has been prepared that incorporate electron-poor aromatic moieties (dpqMe<small><sub>2</sub></small> and dpqPh<small><sub>2</sub></small> chromophores) into tetraazacyclododecane or triazacyclononane based complex structures, and the time-dependent photophysical properties of their Eu(III) and Tb (III) complexes evaluated for the selective and rapid ratiometric analysis of urate in diluted serum solution, together with detailed mechanistic studies probing the nature of the intermediate exciplex and the excited state dynamics using transient absorption spectroscopy.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589165","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}
Yuheng Fu, Bingbing Xie, Miaoxia Liu, Shaojuan Hou, Qunyan Zhu, Alexander Kuhn, Lin Zhang, Wensheng Yang, Neso Sojic
Electrochemiluminescence (ECL) has emerged as a valuable tool for understanding multiphasic and compartmentalized systems, which have crucial wide-ranging applications across diverse fields. However, ECL reactions are limited to the vicinity of the electrode surface due to spatial constraints of electron transfer and the short lifetime of radical species, making ECL emission in bulk multiphasic solution challenging. To address this limitation, we propose a novel bipolar electrochemistry (BPE) approach for wireless dual-color ECL emission at the water/oil (w/o) interface. Firstly, amphiphilic glass carbon (GC) microbeads with distinct hydrophilic and hydrophobic regions are prepared by bipolar electrografting of hydrophobic trifluoromethyl diazonium salt, then the resulting Janus beads are positioned at the w/o interface. Subsequently, two model ECL systems containing luminol and H2O2 in the aqueous phase, and [Ru(bpy)3]²⁺ and benzoyl peroxide (BPO) in the organic phase, are selected based on their solubility to confine light-emitting reactions to their respective phases. Upon application of an electric field perpendicular to the interface, the Janus microbeads get polarized, triggering simultaneous oxidative blue ECL (425 nm) and reductive red ECL (620 nm) in the aqueous and organic phases, respectively. Taking advantage of ECL imaging, the potential gradient distribution on the GC microbead at the w/o interface is revealed, indicating a "pseudo-closed" bipolar system due to limited ion transfer between phases. We also investigate the effect of changing the electric field direction parallel to the interface, which alters the ECL emission area from a hemisphere to a quarter of the microbead's surface. This bipolar ECL approach at the w/o interface not only offers opportunities for imaging the aqueous phase and organic phase simultaneously, but also enables ECL imaging and light generation in the bulk solution, thus overcoming the usual spatial limitation requiring proximity to the electrode surface.
{"title":"Bipolar Electrochemiluminescence at the Water/Organic Interface","authors":"Yuheng Fu, Bingbing Xie, Miaoxia Liu, Shaojuan Hou, Qunyan Zhu, Alexander Kuhn, Lin Zhang, Wensheng Yang, Neso Sojic","doi":"10.1039/d4sc06103a","DOIUrl":"https://doi.org/10.1039/d4sc06103a","url":null,"abstract":"Electrochemiluminescence (ECL) has emerged as a valuable tool for understanding multiphasic and compartmentalized systems, which have crucial wide-ranging applications across diverse fields. However, ECL reactions are limited to the vicinity of the electrode surface due to spatial constraints of electron transfer and the short lifetime of radical species, making ECL emission in bulk multiphasic solution challenging. To address this limitation, we propose a novel bipolar electrochemistry (BPE) approach for wireless dual-color ECL emission at the water/oil (w/o) interface. Firstly, amphiphilic glass carbon (GC) microbeads with distinct hydrophilic and hydrophobic regions are prepared by bipolar electrografting of hydrophobic trifluoromethyl diazonium salt, then the resulting Janus beads are positioned at the w/o interface. Subsequently, two model ECL systems containing luminol and H2O2 in the aqueous phase, and [Ru(bpy)3]²⁺ and benzoyl peroxide (BPO) in the organic phase, are selected based on their solubility to confine light-emitting reactions to their respective phases. Upon application of an electric field perpendicular to the interface, the Janus microbeads get polarized, triggering simultaneous oxidative blue ECL (425 nm) and reductive red ECL (620 nm) in the aqueous and organic phases, respectively. Taking advantage of ECL imaging, the potential gradient distribution on the GC microbead at the w/o interface is revealed, indicating a \"pseudo-closed\" bipolar system due to limited ion transfer between phases. We also investigate the effect of changing the electric field direction parallel to the interface, which alters the ECL emission area from a hemisphere to a quarter of the microbead's surface. This bipolar ECL approach at the w/o interface not only offers opportunities for imaging the aqueous phase and organic phase simultaneously, but also enables ECL imaging and light generation in the bulk solution, thus overcoming the usual spatial limitation requiring proximity to the electrode surface.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580757","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}
Laurent Knerr, Thomas Cogswell, Marie. Ahlqvist, Richard James Lewis, Anneli Nordqvist, Christian Sköld
Conformational control of drug candidates to engineer improved potency and ADME properties is an ongoing area of research. Macrocyclic rings tend to offer a greater degree of rigidity than non-cyclised small molecules, and, as a result they are perfect platforms to instil conformational controls. In this study, the difluoroalkoxyphenyl moiety is examined as a tool to alter the conformation of macrocycles. A fluorinated and non-fluorinated macrocyclic matched pair is compared in terms of conformation preferences and related ADME properties. The synthesised macrocycles are found to give similar major conformations exhibiting a trans amide in the macrocyclic backbone. However, for the fluorinated macrocycle, the major trans amide conformation is in equilibrium with a cis amide minor conformation, seen by 1H NMR in a 4:1 ratio of trans/cis. The conformational fits for the minor fluorinated isomer demonstrate the out of plane preference of the difluoroalkoxy system encouraging the amide within the macrocycle backbone to adopt a cis conformation. A dramatic reduction in metabolic stability was found for the fluorinated macrocycle compared to the non-fluorinated and is postulated to be a result of the interconversion of trans amide to the cis amide, which may be more readily metabolised.
{"title":"The Effect of gem-Difluorination on the Conformation and Properties of a Model Macrocyclic System","authors":"Laurent Knerr, Thomas Cogswell, Marie. Ahlqvist, Richard James Lewis, Anneli Nordqvist, Christian Sköld","doi":"10.1039/d4sc05424e","DOIUrl":"https://doi.org/10.1039/d4sc05424e","url":null,"abstract":"Conformational control of drug candidates to engineer improved potency and ADME properties is an ongoing area of research. Macrocyclic rings tend to offer a greater degree of rigidity than non-cyclised small molecules, and, as a result they are perfect platforms to instil conformational controls. In this study, the difluoroalkoxyphenyl moiety is examined as a tool to alter the conformation of macrocycles. A fluorinated and non-fluorinated macrocyclic matched pair is compared in terms of conformation preferences and related ADME properties. The synthesised macrocycles are found to give similar major conformations exhibiting a trans amide in the macrocyclic backbone. However, for the fluorinated macrocycle, the major trans amide conformation is in equilibrium with a cis amide minor conformation, seen by 1H NMR in a 4:1 ratio of trans/cis. The conformational fits for the minor fluorinated isomer demonstrate the out of plane preference of the difluoroalkoxy system encouraging the amide within the macrocycle backbone to adopt a cis conformation. A dramatic reduction in metabolic stability was found for the fluorinated macrocycle compared to the non-fluorinated and is postulated to be a result of the interconversion of trans amide to the cis amide, which may be more readily metabolised.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580753","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}
N-Perfluoro-tert-butyl (N-PFtB) secondary amines, harboring a unique 19F-reporting moiety linked directly to nitrogen, are highly attractive due to their diverse potential applications. However, their mild and facile synthesis remains a significant challenge. Herein, we present a safe and efficient strategy for the direct synthesis of N-perfluoro-tert-butyl secondary amines from readily available N-trifluoromethyl secondary amines. Experiments and theoretical calculations demonstrate that this novel protocol encompasses three main processes: the elimination of hydrogen fluoride from the N-trifluoromethyl precursor, consecutive addition-elimination conversion of difluoromethyl imine (R-N=CF2) to hexafluoropropyl imine (R-N=C(CF3)2), and final addition of R-N=C(CF3)2 with the in situ generated fluoroform (HCF3). Key advantages of this reaction include the utilization of a single trifluoromethyl source and the N-trifluoromethyl starting material itself as the hydrogen source. Notably, the elimination of hydrogen fluoride, facilitated by CsF, is critical for the success of this approach. This method is compatible with a broad range of functional groups, including heterocyclic compounds. 19F MRI experiments suggest promising prospects for PFtB-labeled secondary amines as 19F MRI contrast agents.
{"title":"Direct synthesis of N-perfluoro-tert-butyl secondary amines from N-trifluoromethyl secondary amines","authors":"leibing Wang, Zhongyu Feng, Zhen Luo, Zihao Guo, Jieping Wang, WenBin Yi","doi":"10.1039/d4sc06335j","DOIUrl":"https://doi.org/10.1039/d4sc06335j","url":null,"abstract":"N-Perfluoro-tert-butyl (N-PFtB) secondary amines, harboring a unique 19F-reporting moiety linked directly to nitrogen, are highly attractive due to their diverse potential applications. However, their mild and facile synthesis remains a significant challenge. Herein, we present a safe and efficient strategy for the direct synthesis of N-perfluoro-tert-butyl secondary amines from readily available N-trifluoromethyl secondary amines. Experiments and theoretical calculations demonstrate that this novel protocol encompasses three main processes: the elimination of hydrogen fluoride from the N-trifluoromethyl precursor, consecutive addition-elimination conversion of difluoromethyl imine (R-N=CF2) to hexafluoropropyl imine (R-N=C(CF3)2), and final addition of R-N=C(CF3)2 with the in situ generated fluoroform (HCF3). Key advantages of this reaction include the utilization of a single trifluoromethyl source and the N-trifluoromethyl starting material itself as the hydrogen source. Notably, the elimination of hydrogen fluoride, facilitated by CsF, is critical for the success of this approach. This method is compatible with a broad range of functional groups, including heterocyclic compounds. 19F MRI experiments suggest promising prospects for PFtB-labeled secondary amines as 19F MRI contrast agents.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580760","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}
Li Li, Wenhan Xu, Guanchun Rui, Shixian Zhang, Qiming Zhang, Qing Wang
Electrostatic capacitors (ECs) are critical components in advanced electronics and electric power systems due to their rapid charge-discharge rate and high power density. While polymers are ideal for ECs due to their high voltage tolerance and mechanical flexibility, their low dielectric constants (K) and limited energy density remain significant limitations. Traditional polymer nanocomposites, which incorporate high-K ceramic fillers, have shown promise in enhancing dielectric properties but often at the cost of electric breakdown strength and scalability. In this Perspective, we explore a pioneering approach that utilizes ultralow loadings of small-sized inorganic nanofillers to significantly improve dielectric constants without compromising other key properties. We delve into the unconventional effects observed in these polymer nanocomposites, including dielectric enhancements, charge trapping, mechanical reinforcements, and microstructural changes, and highlight the impressive energy storage performance achieved with minimal filler contents. We discuss innovative design strategies from viewpoints of polymer and filler structures and showcase recent advancements in nanoscale characterizations and theoretical modelling for understanding the crucial role of polymer-filler interfaces. Finally, we stress fundamental challenges and prospects, providing insights into the transformative potential of these nanocomposites for next-generation energy storage applications.
静电电容器（EC）因其快速充放电速率和高功率密度而成为先进电子和电力系统的关键元件。虽然聚合物具有高耐压性和机械灵活性，是静电电容器的理想材料，但其低介电常数（K）和有限的能量密度仍然是其显著的局限性。传统的聚合物纳米复合材料加入了高 K 陶瓷填料，在增强介电性能方面大有可为，但往往要以电击穿强度和可扩展性为代价。在本《视角》中，我们探讨了一种开创性的方法，即利用超低负载的小尺寸无机纳米填料来显著提高介电常数，同时不影响其他关键性能。我们深入探讨了在这些聚合物纳米复合材料中观察到的非常规效应，包括介电增强、电荷捕获、机械增强和微观结构变化，并重点介绍了在填料含量极低的情况下实现的令人印象深刻的储能性能。我们从聚合物和填料结构的角度讨论了创新设计策略，并展示了纳米级表征和理论建模方面的最新进展，以了解聚合物-填料界面的关键作用。最后，我们强调了基本挑战和前景，为这些纳米复合材料在下一代储能应用中的变革潜力提供了见解。
{"title":"Dilute nanocomposites for capacitive energy storage: progress, challenges and prospects","authors":"Li Li, Wenhan Xu, Guanchun Rui, Shixian Zhang, Qiming Zhang, Qing Wang","doi":"10.1039/d4sc05437g","DOIUrl":"https://doi.org/10.1039/d4sc05437g","url":null,"abstract":"Electrostatic capacitors (ECs) are critical components in advanced electronics and electric power systems due to their rapid charge-discharge rate and high power density. While polymers are ideal for ECs due to their high voltage tolerance and mechanical flexibility, their low dielectric constants (K) and limited energy density remain significant limitations. Traditional polymer nanocomposites, which incorporate high-K ceramic fillers, have shown promise in enhancing dielectric properties but often at the cost of electric breakdown strength and scalability. In this Perspective, we explore a pioneering approach that utilizes ultralow loadings of small-sized inorganic nanofillers to significantly improve dielectric constants without compromising other key properties. We delve into the unconventional effects observed in these polymer nanocomposites, including dielectric enhancements, charge trapping, mechanical reinforcements, and microstructural changes, and highlight the impressive energy storage performance achieved with minimal filler contents. We discuss innovative design strategies from viewpoints of polymer and filler structures and showcase recent advancements in nanoscale characterizations and theoretical modelling for understanding the crucial role of polymer-filler interfaces. Finally, we stress fundamental challenges and prospects, providing insights into the transformative potential of these nanocomposites for next-generation energy storage applications.","PeriodicalId":9909,"journal":{"name":"Chemical Science","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580755","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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