Article
Chemistry, Multidisciplinary
Daniel Richter, Edgars Lakis, Jorn Piel
Summary: The tetrazine ligation is a versatile and fast reaction commonly used for bioorthogonal modifications. However, the incorporation of dienophiles in biomolecules has been limited by the need for externally added reagents. This study introduces a novel strategy, called TyrEx cycloaddition, which enables autonomous dienophile generation in bacteria. This technique has been successfully applied for the labeling of proteins and holds potential for various applications.
Article
Chemistry, Organic
Cathal Caul, Donal F. O'Shea, Dan Wu
Summary: Tetrazine fluorogenic probes and a related model tetrazine were investigated for their reactivity with strained alkyne and alkene dienophiles. The tetrazine probe showed superior reactivity and strong fluorogenic response in aqueous solution. This study demonstrates the potential for real-time observation of intra-cellular fluorogenic cycloadditions in the near-infrared spectral region.
Article
Biochemistry & Molecular Biology
Patrick Keppel, Barbara Sohr, Walter Kuba, Marion Goldeck, Philipp Skrinjar, Jonathan C. T. Carlson, Hannes Mikula
Summary: Bond-cleavage reactions triggered by bioorthogonal tetrazine ligation have been used to chemically control the function of (bio)molecules and activate prodrugs. However, current methods for releasing phenols are limited. To address this issue, we developed a self-immolative linker that connects cleavable amines and phenols, allowing for controlled release of prodrugs.
Review
Biochemistry & Molecular Biology
Gaoxiang Zhao, Zhutie Li, Renshuai Zhang, Liman Zhou, Haibo Zhao, Hongfei Jiang
Summary: Bioorthogonal chemistry represents highly efficient and biocompatible reactions that proceed selectively and rapidly in biological situations. Tetrazine bioorthogonal reactions play an important role in in vivo imaging applications, allowing for the easy tracking of real signals through controlled fluorescence or radiation off-on mechanism.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Organic
Lei Chen, Yuan Yang, Fei Li, Fei Jin, Bin He, Jun Yang
Summary: This study presents a novel synthetic route for producing a stable and versatile cyclopropene precursor, addressing the challenges related to instability and difficulties in scale-up processes. The cyclopropene precursor enables the easy synthesis of various cyclopropenes with different functional groups and handles. Among the synthesized cyclopropene derivatives, the 1-methylcyclopropene uracil nucleoside derivative 40 exhibited the highest second-order kinetic constant when reacting with the 5-TAMRA-Tz fluorescent dye.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Biochemistry & Molecular Biology
Yulin Tian, Ming Fang, Qing Lin
Summary: The intracellular fluorescent labeling of GCGR ICL3 using a bioorthogonal chemistry strategy was achieved successfully, but faced challenges in live-cell imaging studies due to the interference of specific and non-specific signals. Further research is needed to overcome these challenges and improve the specificity of the labeling reactions.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Renshuai Zhang, Jiake Gao, Gaoxiang Zhao, Liman Zhou, Fandong Kong, Tao Jiang, Hongfei Jiang
Summary: Bioorthogonal chemistry allows manipulation of bioactive molecules in living systems with highly selective and biocompatible reactions. Integration of bioorthogonal chemistry with nanotechnologies broadens the biological applications of nanomaterials, with tetrazine bioorthogonal chemistry playing a crucial role due to its rapid kinetics and high selectivity. This advancement has led to developments in various areas of biomedicine.
Editorial Material
Chemistry, Multidisciplinary
Kaiyan Lou, Wanjin Xing, Xiang Meng, Mengyang Chang, Wei Wang
Summary: This article presents a design of high-affinity and high-specificity naphthotube and phenyltetrazine host-guest pairs to control tetrazine reactivity in bioorthogonal chemistry. The study demonstrates the power of this system in precise labeling and functionalization of biological targets in chemical and biological systems, including animal models.
Article
Chemistry, Analytical
Sang-Kee Choi, Youngjun Lee, Sang Eun Yoon, Hongseo Choi, Jonghoon Kim, Jong H. Kim, Sanghee Lee, Wook Kim, Eunha Kim
Summary: This study introduces tetrazine-modified aggregation-induced emission luminogens for bioorthogonal fluorogenic imaging, demonstrating successful development of three different colorful fluorogenic tetrazine-fluorophores with unique fluorescent properties. Tetrazine modification induces fluorescence quenching and a synergistic effect between intramolecular charge transfer and tetrazine-mediated non-radiative decay was revealed through aggregate formation study and computational calculations. Additionally, the simple conjugation between triphenylphosphonium and tetrazine-fluorophore enabled the development of fluorogenic probes for spatiotemporally controlled bioorthogonal bioimaging of mitochondria in live cells without the need for washing the labels.
SENSORS AND ACTUATORS B-CHEMICAL
(2021)
Article
Chemistry, Multidisciplinary
Athanasios Markos, Maurice Biedermann, Johannes Heimgartner, Adeline Schmitt, Kathrin Lang, Helma Wennemers
Summary: In this study, C,N-cyclic-N'-acyl azomethine imines (AMIs) were introduced to bioorthogonal reactions in an aqueous environment, showing stability under physiological conditions and selective reactivity with isonitriles. The AMI-isonitrile ligation demonstrated biocompatibility and orthogonality to commonly used bioorthogonal reactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yayue Wang, Guohua Shen, Jie Li, Wuyu Mao, Hongbao Sun, Ping Feng, Haoxing Wu
Summary: This study reports the bioorthogonal cleavage of methylene tetrazines with ether or ester linkages in the presence of trans-cyclooctene. This approach allows for the controlled release of molecules with phenol or carboxylic acid moieties and has potential applications in various biomedical fields.
Article
Chemistry, Physical
Daniele Loco, Isabelle Chataigner, Jean-Philip Piquemal, Riccardo Spezia
Summary: Modeling chemical reactions using Quantum Chemistry is a widely used predictive strategy that complements experimental studies to understand reaction mechanisms. This research benchmarked various computational approaches for predicting energy barriers in six Diels-Alder reactions of increasing complexity. The results showed that using economical Density Functional Theory methods combined with empirical dispersion corrections can provide high-quality results with minimal computational effort. This simulation protocol opens new prospects for studying Diels-Alder reactions with explicit solvent using hybrid QM/MM molecular dynamics simulations.
Article
Biochemistry & Molecular Biology
Jiayu Sun, Jie Li, Hongbao Sun, Chunling Li, Haoxing Wu
Summary: The study presents the concise synthesis of a series of aryl-functionalized cyclobutene analogues using commercially available starting materials, demonstrating their suitability as stable substrates for bioorthogonal tetrazine ligation.
Article
Chemistry, Multidisciplinary
Jialei Song, Chengling Wu, Yan Zhao, Min Yang, Qingxin Yao, Yuan Gao
Summary: A bioorthogonal disassembly strategy was developed to prompt clearance of supramolecular assemblies within living cells. The enzyme-instructed self-assembly process led to the disruption of pi-pi stacking and induced disassembly of the assemblies, depriving them of potency and addressing their unintended retention and cellular toxicity. This strategy leverages biosafety in developing nanomaterials for drug delivery systems.
Article
Chemistry, Multidisciplinary
Enric Ros, Marina Bellido, Joan A. Matarin, Albert Gallen, Manuel Martinez, Laura Rodriguez, Xavier Verdaguer, Lluis Ribas de Pouplana, Antoni Riera
Summary: A set of 3-bromo-1,2,4,5-tetrazines with distinct substitutions have been used as reagents for late-stage functionalization. Spectroscopic studies showed that tetrazine ethers are intrinsically fluorescent and this fluorescence can be lost through iEDDA cycloaddition. Tetrazine-phenol ethers can undergo rapid iEDDA reactions with a second order rate constant compatible with bioorthogonal ligations. The coupling of 3-bromo-6-methyl-1,2,4,5-tetrazine with l-tyrosine and octreotide demonstrated the detection and reactivity of intrinsically fluorescent tetrazines in a biologically relevant context. The synthesis and characterization of fluorescent tetrazine ethers with bioorthogonal applicability pave the way for the generation of useful compounds for both detection and bioconjugation in vivo.
Article
Chemistry, Multidisciplinary
Ziwei Xi, Hao Kong, Yu Chen, Jiafang Deng, Wenyuan Xu, Yong Liang, Yan Zhang
Summary: The development of new bioorthogonal reactions that are mutually orthogonal to classic bioorthogonal reactions has great importance in providing chemical tools for multiplex labelling of live cells. Here, the first anionic cycloaddend-promoted bioorthogonal cycloaddition reaction between phenanthrene-9,10-dione and furan-2(3H)-one derivatives is reported, which utilizes the high polarity of water to stabilize the highly electron-rich anionic cycloaddend. This metal- and strain-free reaction proceeds rapidly in aqueous solution and on live cells, allowing for mutually orthogonal labelling of three types of proteins or three groups of living cells without cross-talking.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Shuo Lu, Tianyu Zheng, Jiawei Ma, Zhangming Deng, Shengmeng Qin, Yu Chen, Yong Liang
Summary: In this study, a new ionic ligand is developed and successfully used for the para-selective functionalization of aromatic salts. The reaction shows great potential in gram-scale transformation, late-stage elaboration for drug molecules, and diversification of products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jing Shi, Yang Shi, Jian Cheng Li, Wanqing Wei, Yu Chen, Ping Cheng, Cheng Li Liu, Hao Zhang, Rui Wu, Bo Zhang, Rui Hua Jiao, Shouyun Yu, Yong Liang, Ren Xiang Tan, Hui Ming Ge
Summary: This study successfully revealed the mechanism of benzene ring formation in the biosynthesis of cinnamoyl moiety and identified two distinct enzymes that can synthesize benzene rings via polyene precursors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Chang Zhao, Wangjian Sheng, Ying Wang, Jie Zheng, Xiangqian Xie, Yong Liang, Wanqing Wei, Rui Bao, Huan Wang
Summary: Lanthipeptides are a significant group of natural products that require LanP(M1) enzymes to remove N-terminal leader peptides (LPs) during biosynthesis. This study focuses on the biochemical and structural characterization of EryP as a LanP(M1) enzyme involved in the biosynthesis of class III lanthipeptide erythreapeptin. By analyzing the X-ray crystal structures of EryP in different conformations, the researchers identified a unique Ca2+ binding site that regulates the domain dynamics and proteolytic activity. Inspired by this regulatory Ca2+ binding, they developed a strategy to enhance the catalytic activities of LanP(M1) enzymes by strengthening interdomain associations and promoting the conformational equilibrium towards the closed forms.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yu Meng Yang, Er Juan Zhao, Wanqing Wei, Zi Fei Xu, Jing Shi, Xuan Wu, Bo Zhang, Yasuhiro Igarashi, Rui Hua Jiao, Yong Liang, Ren Xiang Tan, Hui Ming Ge
Summary: In this study, a cytochrome P450 enzyme that can catalyze the formation of a benzene ring from an acyclic polyene substrate has been characterized. Through genome mining guided by this P450 enzyme, 12 homologous type I polyketide synthase gene clusters were obtained, among which two clusters were found to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to explore the possible mechanism for the P450-catalyzed benzene ring formation, expanding our knowledge of the catalytic diversity of cytochrome P450.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Medicinal
Wenyuan Xu, Hongzhe Yu, Ruohan Zhao, Yong Liang
Summary: Mitochondria are promising targets in cancer diagnosis and therapeutics. Sydnone and sydnonimine, as mesoionic bioorthogonal reagents, have been used for cell labeling and drug delivery. This study investigated the mitochondrial targeting ability of sydnones and sydnonimines and evaluated the anticancer activities of in-mitochondria delivery of celecoxib, suggesting that celecoxib-induced cancer cell death may not involve mitochondria-related pathway.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Organic
Ruirui Su, Kaili Xie, Yong Liang, K. N. Houk, Fang Liu
Summary: The computational exploration of fluorine-containing substituents in valuable synthetic cycloadditions was prompted by their importance in drug effectiveness. Diels-Alder or 1,3-dipolar cycloaddition reactions of typical reactants involving fluorine-containing substituents (F, CF3, and COCF3) were studied, and the inductive and conjugative effects were found to influence the reactions differently. These results serve as a guide for the design and use of cycloadditions to introduce fluoro and trifluoromethyl substituents in synthetic processes.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Zhenlei Zou, Wenju Chang, Weigang Zhang, Shengyang Ni, Yi Pan, Yong Liang, Donghui Pan, Yi Wang
Summary: Trifluoromethyl copper (CuCF3) is a versatile fluorination reagent widely used in various fluorination reactions. However, its application as a single fluorine source in nucleophilic fluorination reactions is rarely reported. This study presents a general strategy for the rapid synthesis of aliphatic and aromatic acyl fluorides through copper-mediated deoxyfluorination of redox-active esters. The mechanism of CuCF3 forming an [F-CuCF2F5]-intermediate and NHBC ester forming acyl fluoride has been elucidated through DFT calculations.
JOURNAL OF FLUORINE CHEMISTRY
(2023)
Article
Materials Science, Multidisciplinary
Ranran Wang, Chun Zhang, Yuan Chen, Wang Xie, Jianmin Jiao, Yong Liang, Leyong Wang, Juli Jiang
Summary: In this work, a locally rotated molecular tiara Py(5)P5 capable of emitting circularly polarized luminescence (CPL) was designed. The planar chiral skeleton of Py(5)P5 can arrange five pyrene units in an asymmetrical manner to generate CPL emission. The interconversion between pR- and pS-conformers of Py(5)P5 can be freely achieved via local rotation of methoxy groups.
ADVANCED OPTICAL MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Weipeng Li, Yu Chen, Yinghan Chen, Siyu Xia, Wenju Chang, Chengjian Zhu, K. N. Houk, Yong Liang, Jin Xie
Summary: The combination of gold catalysis and silver salt enables selective arylation of amides in unprotected polypeptides, resulting in N-aryl amide peptides with various functional motifs. This method exhibits excellent biocompatibility and has been applied to functionalize peptide drugs and complex peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Longlong Xi, Minyan Wang, Yong Liang, Yue Zhao, Zhuangzhi Shi
Summary: The authors describe a catalytic system that can selectively alkynylate different positions on azaarenes through rhodium catalysis. This method enables precise activation of C-H bonds and offers transformative methods for accessing complex molecular architectures.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Jun-Bin He, Lian Wu, Wanqing Wei, Song Meng, Zheng-Tao Liu, Xuan Wu, Hai-Xue Pan, Sheng Yang, Yong Liang, Jiahai Zhou, Gong-Li Tang
Summary: The construction of O-heterocycles is an important step in organic synthesis and biosynthesis. This study reveals a group of enzymes that catalyze the formation of eight-membered O-heterocycles, rather than the more favored five-membered tetrahydrofuran. The detailed mechanism is elucidated through a combination of biochemical experiments, chemical syntheses, structural analyses, computational simulations, and mutagenesis.
Article
Chemistry, Multidisciplinary
Wenju Chang, Yajun Wang, Yu Chen, Jiawei Ma, Yong Liang
Summary: The origin of regioselectivity in meta-selective C-H borylation of benzamides directed by hydrogen bond interaction between ligand and substrate is explained. A non-directed pathway, where the urea moiety in the ligand interacts with the O atom in Bpin rather than the substrate, competes with the directed pathway and reduces the meta-selectivity. The non-directed pathway can be hindered by introducing a bulky substituent into the urea moiety, leading to improved meta-selectivity in the Ir-catalyzed C-H borylation of previously unsuccessful arenes.
CHINESE CHEMICAL LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Zi-Long Wang, Wanqing Wei, Hai-Dong Wang, Jia-Jing Zhou, Hao-Tian Wang, Kuan Chen, Rong-Shen Wang, Fu-Dong Li, Xue Qiao, Huan Zhou, Yong Liang, Min Ye
Summary: A highly efficient and promiscuous 7,4'-di-O-glycosyltransferase ZjOGT3 was discovered from Ziziphus jujuba var. spinosa. ZjOGT3 exhibited regio-selectivity in sequentially catalyzing the 4'- and 7-O-glycosylation of flavones, as well as selectively catalyzing the 7-O-glycosylation of specific flavones. The crystal structure of ZjOGT3 was determined and the study provides insights into the catalytic mechanisms and synthesis of O-glycosides.
Article
Polymer Science
Xiandong He, Feng Ye, Jia-Cheng Guo, Wenju Chang, Bingxu Ma, Riqing Ding, Sijing Wang, Yong Liang, Dehua Hu, Zi-Hao Guo, Yuguang Ma
Summary: In this study, a N-oxide building block, MeBTzO, was designed and synthesized by oxidizing sp(2)-N in the aromatic ring. Theoretical calculations revealed that MeBTzO exhibited higher reactivity in the direct (hetero)arylation polymerization (DHAP) compared to its non-oxide counterpart, MeBTz. PDPPMeBTzO, a conjugated semiconducting polymer containing N-oxide, was successfully synthesized via DHAP of MeBTzO with DPP. PDPPMeBTzO showed improved electron transport properties, with a higher mu(e) value of 0.11 cm(2) V-1 s(-1) compared to PDPPMeBTz (mu(e) = 7.49 x 10(-3) cm(2) V-1 s(-1)). This research demonstrates the potential of introducing N-oxide groups in conjugated polymers for high performance ambipolar and n-type CSP materials.