Zach Westman, Baoyuan Liu, Kelsey Richardson, Madeleine Davis, Dingyuan Lim, Alan L. Stottlemyer, Christopher S. Letko, Nasim Hooshyar, Vojtech Vlcek, Phillip Christopher, Mahdi M. Abu-Omar
Closed-loop recycling of plastics is needed to bridge the gap between the material demands imposed by a growing global population and the depletion of nonrenewable petroleum feedstocks. Here, we examine chemical recycling of polyurethane foams (PUFs), the sixth most produced polymer in the world, through PUF acidolysis via dicarboxylic acids (DCAs) to release recyclable polyols. Acidolysis enables recycling of the polyol component of PUFs to high-quality materials, and while the influence of DCA structure on recycled PUF quality has been reported, there are no reports that examine the influence of DCA structure on the kinetics of polyol release. Here, we develop quantitative relationships between DCA structure and PUF acidolysis function for ∼10 different DCA reagents. PUF acidolysis kinetics were quantified with ∼1 s time resolution using the rate of carbon dioxide (CO2) gas generation, which is shown to occur concomitantly with polyol release. Pseudo-zeroth-order rate constants were measured as a function of DCA composition, reaction temperature, and DCA concentration, and apparent activation barriers were extracted. Our findings demonstrate that DCA carboxyl group proximity and phase of transport are descriptors of PUF acidolysis rates, rather than expected descriptors like pKa. DCAs with closer proximity acid groups exhibited faster PUF acidolysis rate constants. Furthermore, a shrinking core mechanism effectively describes the kinetic functional form of the kinetics of PUF acidolysis by DCAs. Measurements of acidolysis kinetics for model PUF (M-PUF) and end-of-life PUF (EOL PUF) confirm the applicability of our analysis to postconsumer materials. This work provides insights into the physical and chemical mechanisms controlling acidolysis, which can facilitate the development of efficient closed-loop PUF chemical recycling schemes.
{"title":"Influence of Carboxylic Acid Structure on the Kinetics of Polyurethane Foam Acidolysis to Recycled Polyol","authors":"Zach Westman, Baoyuan Liu, Kelsey Richardson, Madeleine Davis, Dingyuan Lim, Alan L. Stottlemyer, Christopher S. Letko, Nasim Hooshyar, Vojtech Vlcek, Phillip Christopher, Mahdi M. Abu-Omar","doi":"10.1021/jacsau.4c00495","DOIUrl":"https://doi.org/10.1021/jacsau.4c00495","url":null,"abstract":"Closed-loop recycling of plastics is needed to bridge the gap between the material demands imposed by a growing global population and the depletion of nonrenewable petroleum feedstocks. Here, we examine chemical recycling of polyurethane foams (PUFs), the sixth most produced polymer in the world, through PUF acidolysis via dicarboxylic acids (DCAs) to release recyclable polyols. Acidolysis enables recycling of the polyol component of PUFs to high-quality materials, and while the influence of DCA structure on recycled PUF quality has been reported, there are no reports that examine the influence of DCA structure on the kinetics of polyol release. Here, we develop quantitative relationships between DCA structure and PUF acidolysis function for ∼10 different DCA reagents. PUF acidolysis kinetics were quantified with ∼1 s time resolution using the rate of carbon dioxide (CO<sub>2</sub>) gas generation, which is shown to occur concomitantly with polyol release. Pseudo-zeroth-order rate constants were measured as a function of DCA composition, reaction temperature, and DCA concentration, and apparent activation barriers were extracted. Our findings demonstrate that DCA carboxyl group proximity and phase of transport are descriptors of PUF acidolysis rates, rather than expected descriptors like p<i>K</i><sub>a</sub>. DCAs with closer proximity acid groups exhibited faster PUF acidolysis rate constants. Furthermore, a shrinking core mechanism effectively describes the kinetic functional form of the kinetics of PUF acidolysis by DCAs. Measurements of acidolysis kinetics for model PUF (M-PUF) and end-of-life PUF (EOL PUF) confirm the applicability of our analysis to postconsumer materials. This work provides insights into the physical and chemical mechanisms controlling acidolysis, which can facilitate the development of efficient closed-loop PUF chemical recycling schemes.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lenka Horníková, Petr Henke, Pavel Kubát, Jiří Mosinger
Herein, we performed a simple virus capture and photoinactivation procedure using visible light on phosphatidylcholine vesicles. l-α-Phosphatidylcholine vesicles were enriched by viral receptors, GT1b gangliosides, and the nonpolar photosensitizer 5,10,15,20-tetraphenylporphyrin. These vesicles absorb in the blue region of visible light with a high quantum yield of antiviral singlet oxygen, O2 (1Δg). Through the successful incorporation of gangliosides into the structure of vesicles and the encapsulation of photosensitizers in their photoactive and monomeric state, the photogeneration of O2(1Δg) was achieved with high efficiency on demand; this process was triggered by light, and specifically targeting/inactivating viruses were captured on ganglioside receptors due to the short lifetime (3.3 μs) and diffusion pathway (approximately 100 nm) of O2(1Δg). Time-resolved and steady-state luminescence as well as absorption spectroscopy were used to monitor the photoactivity of the photosensitizer and the photogeneration of O2(1Δg) on the surface of the vesicles. The capture of model mouse polyomavirus and its inactivation were achieved using immunofluorescence methods, and loss of infectivity toward mouse fibroblast 3T6 cells was detected.
{"title":"Specifically Targeting Capture and Photoinactivation of Viruses through Phosphatidylcholine-Ganglioside Vesicles with Photosensitizer","authors":"Lenka Horníková, Petr Henke, Pavel Kubát, Jiří Mosinger","doi":"10.1021/jacsau.4c00453","DOIUrl":"https://doi.org/10.1021/jacsau.4c00453","url":null,"abstract":"Herein, we performed a simple virus capture and photoinactivation procedure using visible light on phosphatidylcholine vesicles. <span>l</span>-α-Phosphatidylcholine vesicles were enriched by viral receptors, GT1b gangliosides, and the nonpolar photosensitizer 5,10,15,20-tetraphenylporphyrin. These vesicles absorb in the blue region of visible light with a high quantum yield of antiviral singlet oxygen, O<sub>2</sub> (<sup>1</sup>Δ<sub>g</sub>). Through the successful incorporation of gangliosides into the structure of vesicles and the encapsulation of photosensitizers in their photoactive and monomeric state, the photogeneration of O<sub>2</sub>(<sup>1</sup>Δ<sub>g</sub>) was achieved with high efficiency on demand; this process was triggered by light, and specifically targeting/inactivating viruses were captured on ganglioside receptors due to the short lifetime (3.3 μs) and diffusion pathway (approximately 100 nm) of O<sub>2</sub>(<sup>1</sup>Δ<sub>g</sub>). Time-resolved and steady-state luminescence as well as absorption spectroscopy were used to monitor the photoactivity of the photosensitizer and the photogeneration of O<sub>2</sub>(<sup>1</sup>Δ<sub>g</sub>) on the surface of the vesicles. The capture of model mouse polyomavirus and its inactivation were achieved using immunofluorescence methods, and loss of infectivity toward mouse fibroblast 3T6 cells was detected.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polyethylene terephthalate (PET) and glycerol are prevalent forms of plastic and biowaste, necessitating facile and effective strategies for their upcycling treatment. Herein, we present an innovative one-pot reaction system for the concurrent depolymerization of PET plastics and the transesterification of glycerol into dimethyl terephthalate (DMT), a valuable feedstock in polymer manufacturing. This process occurs in the presence of methyl acetate (MA), a byproduct of the industrial production of acetic acid. The upcycling of biowaste glycerol into glycerol acetates renders them valuable additives for application in both the biofuel and chemical industries. This integrated reaction system enhances the conversion of glycerol to acetins compared with the singular transesterification of glycerol. In this approach, cost-effective catalysts, based on perovskite-structured CaMnO3, were employed. The catalyst undergoes in situ reconstruction in the tandem PET/glycerol/MA system due to glycerolation between the metal oxides and glycerol/acetins. This process results in the formation of small metal oxide nanoparticles confined in amorphous metal glycerolates, thereby enhancing the PET depolymerization efficiency. The optimized coupled reaction system can achieve a product yield exceeding 70% for glycerol acetates and 68% for PET monomers. This research introduces a tandem pathway for the simultaneous upcycling of PET plastic waste and biowaste glycerol with minimal feedstock input and maximal reactant utilization efficiency, promising both economic advantages and positive environmental impacts.
聚对苯二甲酸乙二醇酯（PET）和甘油是塑料和生物废弃物的普遍形式，因此有必要采取简便有效的策略对其进行升级再循环处理。在此，我们提出了一种创新的单锅反应系统，用于同时解聚 PET 塑料和将甘油酯交换成聚合物生产中的重要原料对苯二甲酸二甲酯（DMT）。这一过程是在醋酸甲酯（MA）存在的情况下进行的，醋酸甲酯是醋酸工业生产的副产品。将生物废弃甘油升级回收为醋酸甘油酯，使其成为生物燃料和化工行业的重要添加剂。与单一的甘油酯交换反应相比，这种综合反应系统提高了甘油到醋酸酯的转化率。在这一方法中，采用了基于过氧化物结构 CaMnO3 的高性价比催化剂。由于金属氧化物和甘油/乙炔之间的甘油化作用，催化剂在串联 PET/甘油/MA 体系中发生了原位重构。这一过程导致在无定形金属甘油酯中形成小的金属氧化物纳米颗粒，从而提高了 PET 的解聚效率。经过优化的耦合反应系统可使甘油醋酸酯的产品产率超过 70%，PET 单体的产品产率超过 68%。这项研究为 PET 塑料废料和生物废料甘油的同时升级再循环引入了串联途径，具有最小的原料投入和最高的反应物利用效率，有望带来经济优势和积极的环境影响。
{"title":"Co-upcycling of Plastic Waste and Biowaste via Tandem Transesterification Reactions","authors":"Jiaquan Li, Xingmo Zhang, Xingxu Liu, Xiuping Liao, Jun Huang, Yijiao Jiang","doi":"10.1021/jacsau.4c00459","DOIUrl":"https://doi.org/10.1021/jacsau.4c00459","url":null,"abstract":"Polyethylene terephthalate (PET) and glycerol are prevalent forms of plastic and biowaste, necessitating facile and effective strategies for their upcycling treatment. Herein, we present an innovative one-pot reaction system for the concurrent depolymerization of PET plastics and the transesterification of glycerol into dimethyl terephthalate (DMT), a valuable feedstock in polymer manufacturing. This process occurs in the presence of methyl acetate (MA), a byproduct of the industrial production of acetic acid. The upcycling of biowaste glycerol into glycerol acetates renders them valuable additives for application in both the biofuel and chemical industries. This integrated reaction system enhances the conversion of glycerol to acetins compared with the singular transesterification of glycerol. In this approach, cost-effective catalysts, based on perovskite-structured CaMnO<sub>3</sub>, were employed. The catalyst undergoes in situ reconstruction in the tandem PET/glycerol/MA system due to glycerolation between the metal oxides and glycerol/acetins. This process results in the formation of small metal oxide nanoparticles confined in amorphous metal glycerolates, thereby enhancing the PET depolymerization efficiency. The optimized coupled reaction system can achieve a product yield exceeding 70% for glycerol acetates and 68% for PET monomers. This research introduces a tandem pathway for the simultaneous upcycling of PET plastic waste and biowaste glycerol with minimal feedstock input and maximal reactant utilization efficiency, promising both economic advantages and positive environmental impacts.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pu Chen, Tayla J. Van Oers, Elena Arutyunova, Conrad Fischer, Chaoxiang Wang, Tess Lamer, Marco J. van Belkum, Howard S. Young, John C. Vederas, M. Joanne Lemieux
Ibuzatrelvir (1) was recently disclosed and patented by Pfizer for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has received fast-track status from the USA Food and Drug Administration (FDA) and has entered phase III clinical trials as a possible replacement for Paxlovid. Like nirmatrelvir (2) in Paxlovid, this orally active drug candidate is designed to target viral main proteases (Mpro) through reversible covalent interaction of its nitrile warhead with the active site thiol of the chymotrypsin-like cysteine protease (3CL protease). Inhibition of Mpro hinders the processing of the proteins essential for viral replication in vivo. However, ibuzatrelvir apparently does not require ritonavir (3), which is coadministered in Paxlovid to block human oxidative metabolism of nirmatrelvir. Here, we report the crystal structure of the complex of ibuzatrelvir with the active site of SARS-CoV-2 Mpro at 2.0 Å resolution. In addition, we show that ibuzatrelvir also potently inhibits the Mpro of Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is fortunately not widespread but can be dangerously lethal (∼36% mortality). Co-crystal structures show that the binding mode of the drug to both active sites is similar and that the trifluoromethyl group of the inhibitor fits precisely into a critical S2 substrate binding pocket of the main proteases. However, our results also provide a rationale for the differences in potency of ibuzatrelvir for these two proteases due to minor differences in the substrate preferences leading to a weaker H-bond network in MERS-CoV Mpro. In addition, we examined the reversibility of compound binding to both proteases, which is an important parameter in reducing off-target effects as well as the potential immunogenicity. The crystal structures of the ibuzatrelvir complexes with Mpro of SARS-CoV-2 and of MERS-CoV will further assist drug design for coronaviral infections in humans and animals.
{"title":"A Structural Comparison of Oral SARS-CoV-2 Drug Candidate Ibuzatrelvir Complexed with the Main Protease (Mpro) of SARS-CoV-2 and MERS-CoV","authors":"Pu Chen, Tayla J. Van Oers, Elena Arutyunova, Conrad Fischer, Chaoxiang Wang, Tess Lamer, Marco J. van Belkum, Howard S. Young, John C. Vederas, M. Joanne Lemieux","doi":"10.1021/jacsau.4c00508","DOIUrl":"https://doi.org/10.1021/jacsau.4c00508","url":null,"abstract":"Ibuzatrelvir (1) was recently disclosed and patented by Pfizer for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has received fast-track status from the USA Food and Drug Administration (FDA) and has entered phase III clinical trials as a possible replacement for Paxlovid. Like nirmatrelvir (2) in Paxlovid, this orally active drug candidate is designed to target viral main proteases (M<sup>pro</sup>) through reversible covalent interaction of its nitrile warhead with the active site thiol of the chymotrypsin-like cysteine protease (3CL protease). Inhibition of M<sup>pro</sup> hinders the processing of the proteins essential for viral replication <i>in vivo</i>. However, ibuzatrelvir apparently does not require ritonavir (3), which is coadministered in Paxlovid to block human oxidative metabolism of nirmatrelvir. Here, we report the crystal structure of the complex of ibuzatrelvir with the active site of SARS-CoV-2 M<sup>pro</sup> at 2.0 Å resolution. In addition, we show that ibuzatrelvir also potently inhibits the M<sup>pro</sup> of Middle East respiratory syndrome-related coronavirus (MERS-CoV), which is fortunately not widespread but can be dangerously lethal (∼36% mortality). Co-crystal structures show that the binding mode of the drug to both active sites is similar and that the trifluoromethyl group of the inhibitor fits precisely into a critical S2 substrate binding pocket of the main proteases. However, our results also provide a rationale for the differences in potency of ibuzatrelvir for these two proteases due to minor differences in the substrate preferences leading to a weaker H-bond network in MERS-CoV M<sup>pro</sup>. In addition, we examined the reversibility of compound binding to both proteases, which is an important parameter in reducing off-target effects as well as the potential immunogenicity. The crystal structures of the ibuzatrelvir complexes with M<sup>pro</sup> of SARS-CoV-2 and of MERS-CoV will further assist drug design for coronaviral infections in humans and animals.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141871327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Compared with traditional vaccines, nanoparticulate vaccines are especially suitable for delivering antigens of proteins, peptides, and nucleic acids and facilitating lymph node targeting. Moreover, apart from improving pharmacokinetics and safety, nanoparticulate vaccines assist antigens and molecular adjuvants in crossing biological barriers, targeting immune organs and antigen-presenting cells (APC), controlled release, and cross-presentation. However, the process that stimulates and orchestrates the immune response is complicated, involving spatiotemporal interactions of multiple cell types, including APCs, B cells, T cells, and macrophages. The performance of nanoparticulate vaccines also depends on the microenvironments of the target organs or tissues in different populations. Therefore, it is necessary to develop precise nanoparticulate vaccines that accurately regulate vaccine immune response beyond simply improving pharmacokinetics. This Perspective summarizes and highlights the role of nanoparticulate vaccines with precise size, shape, surface charge, and spatial management of antigen or adjuvant for a precision vaccination in regulating the distribution, targeting, and immune response. It also discusses the importance of the rational design of nanoparticulate vaccines based on the anatomical and immunological microstructure of the target tissues. Moreover, the target delivery and controlled release of nanovaccines should be taken into consideration in designing vaccines for achieving precise immune responses. Additionally, it shows that the nanovaccines remodel the suppressed tumor environment and modulate various immune cell responses which are also essential.
{"title":"Precision Nanovaccines for Potent Vaccination","authors":"Hong Liu, Haolin Chen, Zeyu Yang, Zhenfu Wen, Zhan Gao, Zhijia Liu, Lixin Liu, Yongming Chen","doi":"10.1021/jacsau.4c00568","DOIUrl":"https://doi.org/10.1021/jacsau.4c00568","url":null,"abstract":"Compared with traditional vaccines, nanoparticulate vaccines are especially suitable for delivering antigens of proteins, peptides, and nucleic acids and facilitating lymph node targeting. Moreover, apart from improving pharmacokinetics and safety, nanoparticulate vaccines assist antigens and molecular adjuvants in crossing biological barriers, targeting immune organs and antigen-presenting cells (APC), controlled release, and cross-presentation. However, the process that stimulates and orchestrates the immune response is complicated, involving spatiotemporal interactions of multiple cell types, including APCs, B cells, T cells, and macrophages. The performance of nanoparticulate vaccines also depends on the microenvironments of the target organs or tissues in different populations. Therefore, it is necessary to develop precise nanoparticulate vaccines that accurately regulate vaccine immune response beyond simply improving pharmacokinetics. This Perspective summarizes and highlights the role of nanoparticulate vaccines with precise size, shape, surface charge, and spatial management of antigen or adjuvant for a precision vaccination in regulating the distribution, targeting, and immune response. It also discusses the importance of the rational design of nanoparticulate vaccines based on the anatomical and immunological microstructure of the target tissues. Moreover, the target delivery and controlled release of nanovaccines should be taken into consideration in designing vaccines for achieving precise immune responses. Additionally, it shows that the nanovaccines remodel the suppressed tumor environment and modulate various immune cell responses which are also essential.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuemin Chen, McKenna C. Crawford, Ying Xiong, Anver Basha Shaik, Kiall F. Suazo, Ludwig G. Bauer, Manini S. Penikalapati, Joycelyn H. Williams, Kilian V. M. Huber, Thorkell Andressen, Rolf E. Swenson, Jordan L. Meier
The transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit nonredundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner. Mechanistic studies reveal that selective degradation cannot be predicted solely by target engagement or ternary complex formation, suggesting additional factors govern paralogue-specific degradation. MC-1 inhibits cell proliferation in a subset of cancer cell lines and provides a new tool to investigate the noncatalytic functions of EP300 and CREBBP. Our findings expand the repertoire of EP300/CREBBP-targeting chemical probes and offer insights into the determinants of selective degradation of highly homologous proteins.
{"title":"Paralogue-Selective Degradation of the Lysine Acetyltransferase EP300","authors":"Xuemin Chen, McKenna C. Crawford, Ying Xiong, Anver Basha Shaik, Kiall F. Suazo, Ludwig G. Bauer, Manini S. Penikalapati, Joycelyn H. Williams, Kilian V. M. Huber, Thorkell Andressen, Rolf E. Swenson, Jordan L. Meier","doi":"10.1021/jacsau.4c00442","DOIUrl":"https://doi.org/10.1021/jacsau.4c00442","url":null,"abstract":"The transcriptional coactivators EP300 and CREBBP are critical regulators of gene expression that share high sequence identity but exhibit nonredundant functions in basal and pathological contexts. Here, we report the development of a bifunctional small molecule, MC-1, capable of selectively degrading EP300 over CREBBP. Using a potent aminopyridine-based inhibitor of the EP300/CREBBP catalytic domain in combination with a VHL ligand, we demonstrate that MC-1 preferentially degrades EP300 in a proteasome-dependent manner. Mechanistic studies reveal that selective degradation cannot be predicted solely by target engagement or ternary complex formation, suggesting additional factors govern paralogue-specific degradation. MC-1 inhibits cell proliferation in a subset of cancer cell lines and provides a new tool to investigate the noncatalytic functions of EP300 and CREBBP. Our findings expand the repertoire of EP300/CREBBP-targeting chemical probes and offer insights into the determinants of selective degradation of highly homologous proteins.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chandu G. Krishnan, Hideaki Takano, Hitomi Katsuyama, Wataru Kanna, Hiroki Hayashi, Tsuyoshi Mita
Diphosphine ligands based on cyclobutane, bicyclo[3.1.1]heptane, and bicyclo[4.1.1]octane were synthesized from the corresponding highly strained, small, cyclic organic molecules, i.e., bicyclo[1.1.0]butane, [3.1.1]propellane, and [4.1.1]propellane, employing a ring-opening diphosphination. Under photocatalytic conditions, the three-component reaction of a diarylphosphine oxide, one of the aforementioned strained molecules, and a diarylchlorophosphine results in the smooth formation of the corresponding diphosphines in high yield. The obtained diphosphines can be expected to find applications in functional molecules due to their unique structural characteristics, which likely impart specific properties on their associated metal complexes and coordination polymers (e.g., a zigzag-type structure). The feasibility of the initial radical addition can be estimated using density-functional-theory calculations using the artificial force induced reaction (AFIR) method. This study focuses on the importance of integrating experimental and computational methods for the design and synthesis of new diphosphination reactions that involve strained, small, cyclic organic molecules.
{"title":"Strain-Releasing Ring-Opening Diphosphinations for the Synthesis of Diphosphine Ligands with Cyclic Backbones","authors":"Chandu G. Krishnan, Hideaki Takano, Hitomi Katsuyama, Wataru Kanna, Hiroki Hayashi, Tsuyoshi Mita","doi":"10.1021/jacsau.4c00347","DOIUrl":"https://doi.org/10.1021/jacsau.4c00347","url":null,"abstract":"Diphosphine ligands based on cyclobutane, bicyclo[3.1.1]heptane, and bicyclo[4.1.1]octane were synthesized from the corresponding highly strained, small, cyclic organic molecules, i.e., bicyclo[1.1.0]butane, [3.1.1]propellane, and [4.1.1]propellane, employing a ring-opening diphosphination. Under photocatalytic conditions, the three-component reaction of a diarylphosphine oxide, one of the aforementioned strained molecules, and a diarylchlorophosphine results in the smooth formation of the corresponding diphosphines in high yield. The obtained diphosphines can be expected to find applications in functional molecules due to their unique structural characteristics, which likely impart specific properties on their associated metal complexes and coordination polymers (e.g., a zigzag-type structure). The feasibility of the initial radical addition can be estimated using density-functional-theory calculations using the artificial force induced reaction (AFIR) method. This study focuses on the importance of integrating experimental and computational methods for the design and synthesis of new diphosphination reactions that involve strained, small, cyclic organic molecules.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nguyet A. Nguyen, Jacob H. Forstater, John A. McIntosh
Decarboxylation reactions are frequently found in the biosynthesis of primary and secondary metabolites. Decarboxylase enzymes responsible for these transformations operate via diverse mechanisms and act on a large variety of substrates, making them appealing in terms of biotechnological applications. This Perspective focuses on the occurrence of decarboxylation reactions in natural product biosynthesis and provides a perspective on their applications in biocatalysis for fine chemicals and pharmaceuticals.
{"title":"Decarboxylation in Natural Products Biosynthesis","authors":"Nguyet A. Nguyen, Jacob H. Forstater, John A. McIntosh","doi":"10.1021/jacsau.4c00425","DOIUrl":"https://doi.org/10.1021/jacsau.4c00425","url":null,"abstract":"Decarboxylation reactions are frequently found in the biosynthesis of primary and secondary metabolites. Decarboxylase enzymes responsible for these transformations operate via diverse mechanisms and act on a large variety of substrates, making them appealing in terms of biotechnological applications. This Perspective focuses on the occurrence of decarboxylation reactions in natural product biosynthesis and provides a perspective on their applications in biocatalysis for fine chemicals and pharmaceuticals.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jian Wang, Bo Chao, Jake Piesner, Felice Kelly, Stefanie Kaech Petrie, Xiangshu Xiao, Bingbing X. Li
Protein synthesis and subsequent delivery to the target locations in cells are essential for their proper functions. Methods to label and distinguish newly synthesized proteins from existing ones are critical to assess their differential properties, but such methods are lacking. We describe the first chemical genetics-based approach for selective labeling of existing and newly synthesized proteins that we termed as CG-SLENP. Using HaloTag in-frame fusion with lamin A (LA), we demonstrate that the two pools of proteins can be selectively labeled using CG-SLENP in living cells. We further employ our recently developed selective small molecule ligand LBL1 for LA to probe the potential differences between newly synthesized and existing LA. Our results show that LBL1 can differentially modulate these two pools of LA. These results indicate that the assembly states of newly synthesized LA are distinct from existing LA in living cells. The CG-SLENP method is potentially generalizable to study any cellular proteins.
蛋白质的合成以及随后输送到细胞中的目标位置对其正常功能至关重要。标记和区分新合成蛋白质与现有蛋白质的方法对于评估它们的不同特性至关重要，但目前还缺乏这种方法。我们描述了第一种基于化学遗传学的选择性标记现有蛋白质和新合成蛋白质的方法，我们称之为 CG-SLENP。利用 HaloTag 与层粘连蛋白 A（LA）的框架内融合，我们证明可以在活细胞中使用 CG-SLENP 选择性地标记这两种蛋白池。我们进一步利用最近开发的 LA 选择性小分子配体 LBL1 来探究新合成的 LA 与现有 LA 之间的潜在差异。我们的结果表明，LBL1 可以对这两种 LA 池进行不同程度的调节。这些结果表明，在活细胞中，新合成的 LA 与现有 LA 的组装状态是不同的。CG-SLENP 方法可用于研究任何细胞蛋白质。
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Juliette Zanzi, Zachary Pastorel, Carine Duhayon, Elise Lognon, Christophe Coudret, Antonio Monari, Isabelle M. Dixon, Yves Canac, Michael Smietana, Olivier Baslé
Photocatalysis that uses the energy of light to promote chemical transformations by exploiting the reactivity of excited-state molecules is at the heart of a virtuous dynamic within the chemical community. Visible-light metal-based photosensitizers are most prominent in organic synthesis, thanks to their versatile ligand structure tunability allowing to adjust photocatalytic properties toward specific applications. Nevertheless, a large majority of these photocatalysts are cationic species whose counterion effects remain underestimated and overlooked. In this report, we show that modification of the X counterions constitutive of [Ru(bpy)3](X)2 photocatalysts modulates their catalytic activities in intermolecular [2 + 2] cycloaddition reactions operating through triplet–triplet energy transfer (TTEnT). Particularly noteworthy is the dramatic impact observed in low-dielectric constant solvent over the excited-state quenching coefficient, which varies by two orders of magnitude depending on whether X is a large weakly bound (BArF4–) or a tightly bound (TsO–) anion. In addition, the counterion identity also greatly affects the photophysical properties of the cationic ruthenium complex, with [Ru(bpy)3](BArF4)2 exhibiting the shortest 3MLCT excited-state lifetime, highest excited state energy, and highest photostability, enabling remarkably enhanced performance (up to >1000 TON at a low 500 ppm catalyst loading) in TTEnT photocatalysis. These findings supported by density functional theory-based calculations demonstrate that counterions have a critical role in modulating cationic transition metal-based photocatalyst potency, a parameter that should be taken into consideration also when developing energy transfer-triggered processes.
光催化利用激发态分子的反应活性，利用光的能量促进化学转化，是化学界良性动态的核心。基于可见光的金属光敏剂在有机合成中最为突出，这要归功于其配体结构的多功能可调性，从而可以调整光催化特性以适应特定的应用。然而，这些光催化剂大多是阳离子种类，其反离子效应仍然被低估和忽视。在本报告中，我们发现对[Ru(py)3](X)2 光催化剂构成的 X 反离子进行修饰，可调节其在分子间[2 + 2]环加成反应中通过三重-三重能量转移（TTEnT）进行操作的催化活性。尤其值得注意的是，在低介电常数溶剂中观察到的激发态淬灭系数的巨大影响，根据 X 是大的弱结合阴离子（BArF4-）还是紧结合阴离子（TsO-）的不同，淬灭系数会有两个数量级的变化。此外，反离子的特性也会极大地影响阳离子钌配合物的光物理性质，[Ru(mby)3](BArF4)2 表现出最短的 3MLCT 激发态寿命、最高的激发态能量和最高的光稳定性，从而显著提高了 TTEnT 光催化的性能（在催化剂负载量仅为 500 ppm 的情况下就可达到 1000 吨）。这些基于密度泛函理论的计算结果证明，反离子在调节阳离子过渡金属基光催化剂的效力方面起着至关重要的作用，在开发能量转移触发过程时也应考虑到这一参数。
{"title":"Counterion Effects in [Ru(bpy)3](X)2-Photocatalyzed Energy Transfer Reactions","authors":"Juliette Zanzi, Zachary Pastorel, Carine Duhayon, Elise Lognon, Christophe Coudret, Antonio Monari, Isabelle M. Dixon, Yves Canac, Michael Smietana, Olivier Baslé","doi":"10.1021/jacsau.4c00384","DOIUrl":"https://doi.org/10.1021/jacsau.4c00384","url":null,"abstract":"Photocatalysis that uses the energy of light to promote chemical transformations by exploiting the reactivity of excited-state molecules is at the heart of a virtuous dynamic within the chemical community. Visible-light metal-based photosensitizers are most prominent in organic synthesis, thanks to their versatile ligand structure tunability allowing to adjust photocatalytic properties toward specific applications. Nevertheless, a large majority of these photocatalysts are cationic species whose counterion effects remain underestimated and overlooked. In this report, we show that modification of the X counterions constitutive of [Ru(bpy)<sub>3</sub>](X)<sub>2</sub> photocatalysts modulates their catalytic activities in intermolecular [2 + 2] cycloaddition reactions operating through triplet–triplet energy transfer (TTEnT). Particularly noteworthy is the dramatic impact observed in low-dielectric constant solvent over the excited-state quenching coefficient, which varies by two orders of magnitude depending on whether X is a large weakly bound (BAr<sup>F</sup><sub>4</sub><sup>–</sup>) or a tightly bound (TsO<sup>–</sup>) anion. In addition, the counterion identity also greatly affects the photophysical properties of the cationic ruthenium complex, with [Ru(bpy)<sub>3</sub>](BAr<sup>F</sup><sub>4</sub>)<sub>2</sub> exhibiting the shortest <sup>3</sup>MLCT excited-state lifetime, highest excited state energy, and highest photostability, enabling remarkably enhanced performance (up to >1000 TON at a low 500 ppm catalyst loading) in TTEnT photocatalysis. These findings supported by density functional theory-based calculations demonstrate that counterions have a critical role in modulating cationic transition metal-based photocatalyst potency, a parameter that should be taken into consideration also when developing energy transfer-triggered processes.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141779132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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