Pub Date : 2024-11-08DOI: 10.1038/s42004-024-01343-8
Udyogi N. K. Conthagamage, Rajitha Rajeshwar T, Stijn van der Ham, Nasim Akhtar, Macallister L. Davis, Senuri G. Jayawardana, Lilia Lopez, Hanumantha Rao Vutukuri, Jeremy C. Smith, Micholas Dean Smith, Víctor García-López
Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering. Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines, and could enhance our ability to study and manipulate biological and artificial membranes. Here, the authors introduce a rotaxane with a ring that features two azobenzene photoswitches, and demonstrate that photoswitching can be used to reversibly modulate lipid bilayer structure. This capability was exploited for the light-triggered release of sulforhodamine B from large unilamellar vesicles.
装有致动器的旋转膜具有开发高功能分子机器的巨大潜力。这种系统可以大大提高我们研究和操纵生物膜和人工膜的能力。在这里，我们介绍了一种具有两个偶氮苯光电开关的环状轮烷，它们保持了光可逆性，并能在溶液中沿着轴随机穿梭。在分子动力学模拟支持下对模型双分子层进行的研究表明，偶氮苯光开关如何改变轮烷与周围脂质的相互作用，从而导致脂质堆积的变化。脂质双分子层中的这种变化被用来诱导光触发的磺胺多巴胺 B 从大型单层囊泡中释放出来。此外，光激活轮烷还能诱导巨型单拉米尔小泡的可逆收缩和扩张。这些结果为了解轮烷在脂质双分子层中的相互作用和运作及其对膜特性的影响提供了新的视角。这将有助于开发用于生物医学和生物工程应用的精确膜操纵系统。装有致动器的转轴具有开发高功能分子机器的巨大潜力，可以提高我们研究和操纵生物膜和人工膜的能力。在本文中，作者介绍了一种具有两个偶氮苯光电开关的环状轮烷，并证明光电开关可用于可逆地调节脂质双分子层结构。利用这种能力，光触发了磺胺多巴胺 B 从大型单拉米尔囊泡中的释放。
{"title":"Rotaxanes with a photoresponsive macrocycle modulate the lipid bilayers of large and giant unilamellar vesicles","authors":"Udyogi N. K. Conthagamage, Rajitha Rajeshwar T, Stijn van der Ham, Nasim Akhtar, Macallister L. Davis, Senuri G. Jayawardana, Lilia Lopez, Hanumantha Rao Vutukuri, Jeremy C. Smith, Micholas Dean Smith, Víctor García-López","doi":"10.1038/s42004-024-01343-8","DOIUrl":"10.1038/s42004-024-01343-8","url":null,"abstract":"Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines. Such systems could significantly enhance our ability to study and manipulate biological and artificial membranes. Here, we introduce a rotaxane with a ring featuring two azobenzene photoswitches, which retain their photoreversibility and can be stochastically shuttled along the axle in solution. Studies in model bilayers, supported by molecular dynamics simulations, show how azobenzene photoswitching alters the interaction of rotaxanes with surrounding lipids, leading to changes in lipid packing. Such changes in the lipid bilayer were leveraged to induce the light-triggered release of sulforhodamine B from large unilamellar vesicles. Additionally, light activation of the rotaxanes is shown to induce reversible contraction and expansion of giant unilamellar vesicles. The results provide novel insights into the interactions and operation of rotaxanes in lipid bilayers and their impact on membrane properties. This will aid in developing systems for precise membrane manipulation for applications in biomedicine and bioengineering. Rotaxanes equipped with actuators hold great potential for developing highly functional molecular machines, and could enhance our ability to study and manipulate biological and artificial membranes. Here, the authors introduce a rotaxane with a ring that features two azobenzene photoswitches, and demonstrate that photoswitching can be used to reversibly modulate lipid bilayer structure. This capability was exploited for the light-triggered release of sulforhodamine B from large unilamellar vesicles.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01343-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-07DOI: 10.1038/s42004-024-01334-9
Maximilián Lamanec, Svatopluk Civiš, Pavel Hobza
Previously studied complexes with protonic and hydridic hydrogen bonds exhibit significant similarities. The present study provides a detailed investigation of the structure, stabilization, electronic properties, and spectral characteristics of protonic and hydridic hydrogen bonds using low-temperature infrared (IR) spectroscopy and computational methods. Complexes of pentafluorobenzene with ammonia (C₆F₅H⋯NH₃) and triethylgermane with trifluoroiodomethane (Et₃GeH⋯ICF₃) were analyzed using both experimental and computational tools. Additionally, 30 complexes with protonic hydrogen bonds and 30 complexes with hydridic hydrogen bonds were studied computationally. Our findings reveal that, despite the opposite atomic charges on the hydrogens in these hydrogen bonds, and consequently the opposite directions of electron transfer in protonic and hydridic hydrogen bonds, their spectral manifestations - specifically, the red shifts in the X–H stretching frequency and the increase in intensity - are remarkably similar. The study also discusses the limitations of the current IUPAC definition of hydrogen bonding in covering both types of H-bonds and suggests a way to overcome these limitations. Understanding hydrogen-bonding is essential for many fields of natural science. Here, the authors investigate protonic and hydridic hydrogen bonds using low-temperature infrared spectroscopy and computational methods, finding that despite opposite atomic charges on the hydrogens in these hydrogen bonds their spectral manifestations are remarkably similar.
{"title":"On the similar spectral manifestations of protonic and hydridic hydrogen bonds despite their different origin","authors":"Maximilián Lamanec, Svatopluk Civiš, Pavel Hobza","doi":"10.1038/s42004-024-01334-9","DOIUrl":"10.1038/s42004-024-01334-9","url":null,"abstract":"Previously studied complexes with protonic and hydridic hydrogen bonds exhibit significant similarities. The present study provides a detailed investigation of the structure, stabilization, electronic properties, and spectral characteristics of protonic and hydridic hydrogen bonds using low-temperature infrared (IR) spectroscopy and computational methods. Complexes of pentafluorobenzene with ammonia (C₆F₅H⋯NH₃) and triethylgermane with trifluoroiodomethane (Et₃GeH⋯ICF₃) were analyzed using both experimental and computational tools. Additionally, 30 complexes with protonic hydrogen bonds and 30 complexes with hydridic hydrogen bonds were studied computationally. Our findings reveal that, despite the opposite atomic charges on the hydrogens in these hydrogen bonds, and consequently the opposite directions of electron transfer in protonic and hydridic hydrogen bonds, their spectral manifestations - specifically, the red shifts in the X–H stretching frequency and the increase in intensity - are remarkably similar. The study also discusses the limitations of the current IUPAC definition of hydrogen bonding in covering both types of H-bonds and suggests a way to overcome these limitations. Understanding hydrogen-bonding is essential for many fields of natural science. Here, the authors investigate protonic and hydridic hydrogen bonds using low-temperature infrared spectroscopy and computational methods, finding that despite opposite atomic charges on the hydrogens in these hydrogen bonds their spectral manifestations are remarkably similar.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01334-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The attraction between π-conjugated planar electron donor and acceptor molecules that form many stable charge-transfer (CT) complexes has been explained by quantum chemical CT interactions, although the fundamental origin remains unclear. Here, we demonstrate the mechanism of CT complex formation by potential energy map analysis for TTF–CA and BTBT–TCNQ, using energy decomposition of intermolecular interaction by symmetry-adapted perturbation theory (SAPT) combined with coupled cluster calculation. We find that the source of attraction between donor and acceptor molecules is ascribed primarily to the dispersion force and also to the electrostatic force. In contrast, the contribution of CT interactions to the attractive forces is minimal. We demonstrate that the highly directional feature of the exchange repulsion force, coupled with the attractive dispersion and electrostatic forces, is crucial in determining the intermolecular arrangements of actual CT crystals. These findings are key for understanding the unique structural and electronic properties of π-conjugated CT complexes. The attraction between π-conjugated planar electron donor and acceptor molecules within charge–transfer (CT) complexes has been explained by quantum chemical CT interactions, but its fundamental origins remain unclear. Here, the authors combine symmetry-adapted perturbation theory with coupled cluster calculations to probe the mechanism of CT complex formation in crystals, finding that dispersion and electrostatic forces are dominant, with significant directional exchange repulsion.
{"title":"Origin of the intermolecular forces that produce donor–acceptor stacks in π-conjugated charge-transfer complexes","authors":"Seiji Tsuzuki, Ryota Ono, Satoru Inoue, Satoshi Matsuoka, Tatsuo Hasegawa","doi":"10.1038/s42004-024-01329-6","DOIUrl":"10.1038/s42004-024-01329-6","url":null,"abstract":"The attraction between π-conjugated planar electron donor and acceptor molecules that form many stable charge-transfer (CT) complexes has been explained by quantum chemical CT interactions, although the fundamental origin remains unclear. Here, we demonstrate the mechanism of CT complex formation by potential energy map analysis for TTF–CA and BTBT–TCNQ, using energy decomposition of intermolecular interaction by symmetry-adapted perturbation theory (SAPT) combined with coupled cluster calculation. We find that the source of attraction between donor and acceptor molecules is ascribed primarily to the dispersion force and also to the electrostatic force. In contrast, the contribution of CT interactions to the attractive forces is minimal. We demonstrate that the highly directional feature of the exchange repulsion force, coupled with the attractive dispersion and electrostatic forces, is crucial in determining the intermolecular arrangements of actual CT crystals. These findings are key for understanding the unique structural and electronic properties of π-conjugated CT complexes. The attraction between π-conjugated planar electron donor and acceptor molecules within charge–transfer (CT) complexes has been explained by quantum chemical CT interactions, but its fundamental origins remain unclear. Here, the authors combine symmetry-adapted perturbation theory with coupled cluster calculations to probe the mechanism of CT complex formation in crystals, finding that dispersion and electrostatic forces are dominant, with significant directional exchange repulsion.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":5.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-05DOI: 10.1038/s42004-024-01337-6
Moritz Stappert, Daniel Kohnhäuser, Tim Seedorf, Janetta Coetzee, Katharina Rox, Hazel L. S. Fuchs, Katarina Cirnski, Christian Leitner, Jennifer Herrmann, Andreas Kirschning, Rolf Müller, Mark Brönstrup
Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. The cystobactamids, discovered from myxobacterial sources, have a unique hexapeptidic scaffold with five arylamides and possess potent, resistance-breaking properties. This study investigates the role of the central D-ring pharmacophore in cystobactamids, a para-aminobenzoic acid (PABA) moiety that is additionally substituted by hydroxy and isopropoxy functions. We varied the two oxygenated substituents and replaced both amide connectors with bioisosteres. Synthetic routes were developed that included metal-mediated aromatic functionalization or heterocycle formations, leading to 19 novel analogues. The antibiotic efficacy of all analogues was determined against bacteria from the ESKAPE pathogen panel. While the replacement and the repositioning of hydroxy and isopropoxy substituents was not advantageous, exchanging PABA by terephthalic acid amides led to the highly potent analogue 42 with broad-spectrum activity, insensitivity towards AlbD-mediated degradation and promising pharmacokinetic properties in mice. The study highlights the steep structure-activity relationships in the tetrasubstituted D-ring and a surprisingly favorable reversion of the amide connecting C and D. Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. Here, the authors assess the role of the central D ring pharmacophore in cystobactamids, and develop a potent broad-spectrum antibiotic by exchanging a para-aminobenzoic acid with a terephthalic acid amide.
由于抗菌药耐药性的增加，广谱抗生素的新型支架十分罕见，而且需求量很大。从霉菌中发现的胱内酰胺类药物具有独特的六肽支架，包含五个芳基酰胺，具有强效的抗药性。本研究探讨了胱内酰胺类药物的中心 D 环药理作用，即对氨基苯甲酸（PABA）分子，该分子还被羟基和异丙氧基功能取代。我们改变了这两个含氧取代基，并用生物异构体取代了两个酰胺连接体。我们开发了包括金属介导的芳香族官能化或杂环形成在内的合成路线，最终得到了 19 种新型类似物。所有类似物对 ESKAPE 病原体样本中细菌的抗生素疗效均已确定。虽然羟基和异丙氧基取代基的置换和重新定位没有优势，但用对苯二甲酸酰胺置换 PABA 可得到具有广谱活性、对 AlbD 介导的降解不敏感以及在小鼠体内具有良好药代动力学特性的强效类似物 42。该研究强调了四取代 D 环陡峭的结构-活性关系，以及连接 C 和 D 的酰胺令人惊讶的有利还原。
{"title":"Synthetic studies on the tetrasubstituted D-ring of cystobactamids lead to potent terephthalic acid antibiotics","authors":"Moritz Stappert, Daniel Kohnhäuser, Tim Seedorf, Janetta Coetzee, Katharina Rox, Hazel L. S. Fuchs, Katarina Cirnski, Christian Leitner, Jennifer Herrmann, Andreas Kirschning, Rolf Müller, Mark Brönstrup","doi":"10.1038/s42004-024-01337-6","DOIUrl":"10.1038/s42004-024-01337-6","url":null,"abstract":"Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. The cystobactamids, discovered from myxobacterial sources, have a unique hexapeptidic scaffold with five arylamides and possess potent, resistance-breaking properties. This study investigates the role of the central D-ring pharmacophore in cystobactamids, a para-aminobenzoic acid (PABA) moiety that is additionally substituted by hydroxy and isopropoxy functions. We varied the two oxygenated substituents and replaced both amide connectors with bioisosteres. Synthetic routes were developed that included metal-mediated aromatic functionalization or heterocycle formations, leading to 19 novel analogues. The antibiotic efficacy of all analogues was determined against bacteria from the ESKAPE pathogen panel. While the replacement and the repositioning of hydroxy and isopropoxy substituents was not advantageous, exchanging PABA by terephthalic acid amides led to the highly potent analogue 42 with broad-spectrum activity, insensitivity towards AlbD-mediated degradation and promising pharmacokinetic properties in mice. The study highlights the steep structure-activity relationships in the tetrasubstituted D-ring and a surprisingly favorable reversion of the amide connecting C and D. Novel scaffolds for broad-spectrum antibiotics are rare and in strong demand because of the increase in antimicrobial resistance. Here, the authors assess the role of the central D ring pharmacophore in cystobactamids, and develop a potent broad-spectrum antibiotic by exchanging a para-aminobenzoic acid with a terephthalic acid amide.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42004-024-01330-z
Abhilash Rana, Ruchi Chauhan, Amirreza Mottafegh, Dong Pyo Kim, Ajay K. Singh
The reproducibility of chemical reactions, when obtaining protocols from literature or databases, is highly challenging for academicians, industry professionals and even now for the machine learning process. To synthesize the organic molecule under the photochemical condition, several years for the reaction optimization, highly skilled manpower, long reaction time etc. are needed, resulting in non-affordability and slow down the research and development. Herein, we have introduced the DigiChemTree backed with the artificial intelligence to auto-optimize the photochemical reaction parameter and synthesizing the on demand library of the molecules in fast manner. Newly, auto-generated digital code was further tested for the late stage functionalization of the various active pharmaceutical ingredient. Light-induced reactions of diazo compounds have become crucial in organic synthesis and drug discovery, however, optimization of reaction conditions is still very time-consuming. Here, the authors develop a DigiChemTree platform using artificial intelligence to auto-optimize the photochemical reaction parameters and rapidly synthesize an on-demand library of molecules.
{"title":"DigiChemTree enables programmable light-induced carbene generation for on demand chemical synthesis","authors":"Abhilash Rana, Ruchi Chauhan, Amirreza Mottafegh, Dong Pyo Kim, Ajay K. Singh","doi":"10.1038/s42004-024-01330-z","DOIUrl":"10.1038/s42004-024-01330-z","url":null,"abstract":"The reproducibility of chemical reactions, when obtaining protocols from literature or databases, is highly challenging for academicians, industry professionals and even now for the machine learning process. To synthesize the organic molecule under the photochemical condition, several years for the reaction optimization, highly skilled manpower, long reaction time etc. are needed, resulting in non-affordability and slow down the research and development. Herein, we have introduced the DigiChemTree backed with the artificial intelligence to auto-optimize the photochemical reaction parameter and synthesizing the on demand library of the molecules in fast manner. Newly, auto-generated digital code was further tested for the late stage functionalization of the various active pharmaceutical ingredient. Light-induced reactions of diazo compounds have become crucial in organic synthesis and drug discovery, however, optimization of reaction conditions is still very time-consuming. Here, the authors develop a DigiChemTree platform using artificial intelligence to auto-optimize the photochemical reaction parameters and rapidly synthesize an on-demand library of molecules.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1038/s42004-024-01321-0
Coral Hillel, Sara Rough, Christopher J. Barrett, William J. Pietro, Ozzy Mermut
Many studies of azobenzene photoswitches are carried out in polar aprotic solvents as a first principles characterization of thermal isomerization. Among the most convenient polar aprotic solvents are chlorinated hydrocarbons, such as DCM. However, studies of azobenzene thermal isomerization in such solvents have led to spurious, inconclusive, and irreproducible results, even when scrupulously cleaned and dried, a phenomenon not well understood. We present the results of a comprehensive investigation into the root cause of this problem. We explain how irradiation of an azopyridine photoswitch with UV in DCM acts not just as a trigger for photoisomerization, but protonation of the pyridine moiety through photodecomposition of the solvent. Protonation markedly accelerates the thermal isomerization rate, and DFT calculations demonstrate that the singlet-triplet rotation mechanism assumed for many azo photoswitches is surprisingly abolished. This study implies exploitative advantages of photolytically-generated protons and finally explains the warning against using chlorinated solvent with UV irradiation in isomerization experiments. Azobenzenes undergo reversible light-induced photoisomerization, resulting in marked spectroscopic, electronic, and mechanical changes, but their sensitivity towards solvents is not fully understood. Here, the authors report how irradiation of an azopyridine photoswitch with UV light in dichloromethane triggers protonation of the pyridine moiety through photodecomposition of the solvent, consequently accelerating thermal back isomerization and abolishing singlet-triplet rotation mechanisms.
{"title":"A cautionary tale of basic azo photoswitching in dichloromethane finally explained","authors":"Coral Hillel, Sara Rough, Christopher J. Barrett, William J. Pietro, Ozzy Mermut","doi":"10.1038/s42004-024-01321-0","DOIUrl":"10.1038/s42004-024-01321-0","url":null,"abstract":"Many studies of azobenzene photoswitches are carried out in polar aprotic solvents as a first principles characterization of thermal isomerization. Among the most convenient polar aprotic solvents are chlorinated hydrocarbons, such as DCM. However, studies of azobenzene thermal isomerization in such solvents have led to spurious, inconclusive, and irreproducible results, even when scrupulously cleaned and dried, a phenomenon not well understood. We present the results of a comprehensive investigation into the root cause of this problem. We explain how irradiation of an azopyridine photoswitch with UV in DCM acts not just as a trigger for photoisomerization, but protonation of the pyridine moiety through photodecomposition of the solvent. Protonation markedly accelerates the thermal isomerization rate, and DFT calculations demonstrate that the singlet-triplet rotation mechanism assumed for many azo photoswitches is surprisingly abolished. This study implies exploitative advantages of photolytically-generated protons and finally explains the warning against using chlorinated solvent with UV irradiation in isomerization experiments. Azobenzenes undergo reversible light-induced photoisomerization, resulting in marked spectroscopic, electronic, and mechanical changes, but their sensitivity towards solvents is not fully understood. Here, the authors report how irradiation of an azopyridine photoswitch with UV light in dichloromethane triggers protonation of the pyridine moiety through photodecomposition of the solvent, consequently accelerating thermal back isomerization and abolishing singlet-triplet rotation mechanisms.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1038/s42004-024-01335-8
Marta J. I. Airaghi Leccardi, Benoît X. E. Desbiolles, Anna Y. Haddad, Baju C. Joy, Chen Song, Deblina Sarkar
Neurons are essential cells composing our nervous system and orchestrating our body, thoughts, and emotions. Recently, research efforts have been focused on studying not only their collective structure and functions but also the single-cell properties as an individual complex system. Nanoscale technology has the potential to unravel mysteries in neuroscience and provide support to the neuron by measuring and influencing several aspects of the cell. As wearable devices interact with different parts of our body, we could envision a thousand times smaller interface to conform on and around subcellular regions of the neurons for unprecedented contact, probing, and control. However, a major challenge is to develop an interface that can morph to the extreme curvatures of subcellular structures. Here, we address this challenge with the development of a platform that conforms even to small neuronal processes. To achieve this, we produced a wireless platform made of an azobenzene polymer that undergoes on-demand light-induced folding with sub-micrometer radius of curvature. We show that these platforms can be fabricated with an adjustable form factor, micro-injected onto neuronal cultures, and can delicately wrap various morphologies of neuronal processes in vitro, toward obtaining seamless biointerfaces with an increased coupling with the cell membrane. Our in vitro testings did not show any adverse effects of the platforms in contact with the neurons. Additionally, for future functionality, nanoparticles or optoelectronic materials could be blended with the azobenzene polymer, and 2D materials on the platform surface could be safely folded to the high curvatures without mechanical failure, as per our calculations. Ultimately, this technology could lay the foundation for future integration of wirelessly actuated materials within or on its platform for neuromodulation, recording, and neuroprotection at the subcellular level. Neuronal behavior can be controlled by probing and modulating subcellular regions of the cells; however, developing an interface that can morph into the extreme curvatures of neurites is a major challenge. Here, the authors develop a wireless platform made of an azobenzene polymer that undergoes on-demand light-induced folding with an ultra-low curvature radius and wraps various morphologies of neuronal processes in vitro.
{"title":"Light-induced rolling of azobenzene polymer thin films for wrapping subcellular neuronal structures","authors":"Marta J. I. Airaghi Leccardi, Benoît X. E. Desbiolles, Anna Y. Haddad, Baju C. Joy, Chen Song, Deblina Sarkar","doi":"10.1038/s42004-024-01335-8","DOIUrl":"10.1038/s42004-024-01335-8","url":null,"abstract":"Neurons are essential cells composing our nervous system and orchestrating our body, thoughts, and emotions. Recently, research efforts have been focused on studying not only their collective structure and functions but also the single-cell properties as an individual complex system. Nanoscale technology has the potential to unravel mysteries in neuroscience and provide support to the neuron by measuring and influencing several aspects of the cell. As wearable devices interact with different parts of our body, we could envision a thousand times smaller interface to conform on and around subcellular regions of the neurons for unprecedented contact, probing, and control. However, a major challenge is to develop an interface that can morph to the extreme curvatures of subcellular structures. Here, we address this challenge with the development of a platform that conforms even to small neuronal processes. To achieve this, we produced a wireless platform made of an azobenzene polymer that undergoes on-demand light-induced folding with sub-micrometer radius of curvature. We show that these platforms can be fabricated with an adjustable form factor, micro-injected onto neuronal cultures, and can delicately wrap various morphologies of neuronal processes in vitro, toward obtaining seamless biointerfaces with an increased coupling with the cell membrane. Our in vitro testings did not show any adverse effects of the platforms in contact with the neurons. Additionally, for future functionality, nanoparticles or optoelectronic materials could be blended with the azobenzene polymer, and 2D materials on the platform surface could be safely folded to the high curvatures without mechanical failure, as per our calculations. Ultimately, this technology could lay the foundation for future integration of wirelessly actuated materials within or on its platform for neuromodulation, recording, and neuroprotection at the subcellular level. Neuronal behavior can be controlled by probing and modulating subcellular regions of the cells; however, developing an interface that can morph into the extreme curvatures of neurites is a major challenge. Here, the authors develop a wireless platform made of an azobenzene polymer that undergoes on-demand light-induced folding with an ultra-low curvature radius and wraps various morphologies of neuronal processes in vitro.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-12"},"PeriodicalIF":5.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With peculiar structural features at the surface of small metal nanoparticles, some discrete sites can display catalytic behaviour similar to what could be observed with mononuclear metal catalysts in solution. We have studied the transfer of two catalytic tandem reactions from homogeneous to heterogeneous conditions. Tandem cyclisation/reduction of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au nanoparticles over TiO2 (Au NPs/TiO2) in the presence of Hantzsch ester with 45-98% yields for 15 examples (average yield: 70.4%). Similarly, tandem cyclisation/hydroalkoxylation of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au NPs/TiO2 in methanol or other alcohols with 62-96% yields for 17 examples (average yield: 84.9%). The application potential of this catalytic system was demonstrated with the total synthesis of a bioactive isochromene derivative featuring one of the developed reactions as the key step and the implementation of the tandem cyclisation/hydroalkoxylation in a continuous flow reactor, scaling up the reaction by a factor of 10 without loss of efficiency. Heterogeneous catalysis offers a range of advantages over homogeneous catalysis, but transferring a reaction from homogeneous to heterogeneous protocols is highly challenging. Here, the authors study the transfer of two catalytic tandem reactions—a cyclization/reduction and a cyclization/hydroalkoxylation—from homogeneous to heterogeneous conditions, using gold nanoparticles to generate isochromene derivatives from ortho-alkynyl benzaldehyde starting materials, and demonstrating scalability in flow.
{"title":"Small gold nanoparticles for tandem cyclization/reduction and cyclization/hydroalkoxylation reactions","authors":"Kristína Plevová, Véronique Michelet, Sylvain Antoniotti","doi":"10.1038/s42004-024-01336-7","DOIUrl":"10.1038/s42004-024-01336-7","url":null,"abstract":"With peculiar structural features at the surface of small metal nanoparticles, some discrete sites can display catalytic behaviour similar to what could be observed with mononuclear metal catalysts in solution. We have studied the transfer of two catalytic tandem reactions from homogeneous to heterogeneous conditions. Tandem cyclisation/reduction of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au nanoparticles over TiO2 (Au NPs/TiO2) in the presence of Hantzsch ester with 45-98% yields for 15 examples (average yield: 70.4%). Similarly, tandem cyclisation/hydroalkoxylation of ortho-alkynyl benzaldehyde derivatives was successfully achieved with Au NPs/TiO2 in methanol or other alcohols with 62-96% yields for 17 examples (average yield: 84.9%). The application potential of this catalytic system was demonstrated with the total synthesis of a bioactive isochromene derivative featuring one of the developed reactions as the key step and the implementation of the tandem cyclisation/hydroalkoxylation in a continuous flow reactor, scaling up the reaction by a factor of 10 without loss of efficiency. Heterogeneous catalysis offers a range of advantages over homogeneous catalysis, but transferring a reaction from homogeneous to heterogeneous protocols is highly challenging. Here, the authors study the transfer of two catalytic tandem reactions—a cyclization/reduction and a cyclization/hydroalkoxylation—from homogeneous to heterogeneous conditions, using gold nanoparticles to generate isochromene derivatives from ortho-alkynyl benzaldehyde starting materials, and demonstrating scalability in flow.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01336-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1038/s42004-024-01328-7
Farzad Molani, Art E. Cho
Accurate prediction of binding free energy is crucial for the rational design of drug candidates and understanding protein-ligand interactions. To address this, we have developed four protocols that combine QM/MM calculations and the mining minima (M2) method, tested on 9 targets and 203 ligands. Our protocols carry out free energy processing with or without conformational search on the selected conformers obtained from M2 calculations, where their force field atomic charge parameters are substituted with those obtained from a QM/MM calculation. The method achieved a high Pearson’s correlation coefficient (0.81) with experimental binding free energies across diverse targets, demonstrating its generality. Using a differential evolution algorithm with a universal scaling factor of 0.2, we achieved a low mean absolute error of 0.60 kcal mol-1. This performance surpasses many existing methods and is comparable to popular relative binding free energy techniques but at significantly lower computational cost. Binding free energy calculations are crucial in computational drug discovery, however, the current alchemical free energy perturbation (FEP) requires large computational capabilities to achieve high accuracy. Here, the authors develop an alternative method by combining QM/MM and the mining minima method to predict free energies at lower computational cost and with comparable accuracy to FEP-based methods.
{"title":"Accurate protein-ligand binding free energy estimation using QM/MM on multi-conformers predicted from classical mining minima","authors":"Farzad Molani, Art E. Cho","doi":"10.1038/s42004-024-01328-7","DOIUrl":"10.1038/s42004-024-01328-7","url":null,"abstract":"Accurate prediction of binding free energy is crucial for the rational design of drug candidates and understanding protein-ligand interactions. To address this, we have developed four protocols that combine QM/MM calculations and the mining minima (M2) method, tested on 9 targets and 203 ligands. Our protocols carry out free energy processing with or without conformational search on the selected conformers obtained from M2 calculations, where their force field atomic charge parameters are substituted with those obtained from a QM/MM calculation. The method achieved a high Pearson’s correlation coefficient (0.81) with experimental binding free energies across diverse targets, demonstrating its generality. Using a differential evolution algorithm with a universal scaling factor of 0.2, we achieved a low mean absolute error of 0.60 kcal mol-1. This performance surpasses many existing methods and is comparable to popular relative binding free energy techniques but at significantly lower computational cost. Binding free energy calculations are crucial in computational drug discovery, however, the current alchemical free energy perturbation (FEP) requires large computational capabilities to achieve high accuracy. Here, the authors develop an alternative method by combining QM/MM and the mining minima method to predict free energies at lower computational cost and with comparable accuracy to FEP-based methods.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01328-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1038/s42004-024-01323-y
Dr Aude Sadet is a junior scientist who conducts research in the Biophysics and Biomedical Applications Laboratory at the Extreme Light Infrastructure of the National Research Institute for Physics in Magurele, Bucharest, Romania.
{"title":"Women in chemistry: Q&A with Dr Aude Sadet","authors":"","doi":"10.1038/s42004-024-01323-y","DOIUrl":"10.1038/s42004-024-01323-y","url":null,"abstract":"Dr Aude Sadet is a junior scientist who conducts research in the Biophysics and Biomedical Applications Laboratory at the Extreme Light Infrastructure of the National Research Institute for Physics in Magurele, Bucharest, Romania.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-2"},"PeriodicalIF":5.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01323-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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