Recently, the School of Science of our university published the latest research results entitled “Novel Light-Promoted Bioorthogonal Reaction via Molecular Recombination for the Synthesis of Polysubstituted Pyrrole and its Application in Vitro and in Vivo Studies”. 2023 M.S. student Aoting Ni, Ph.D. student Chenlu Zhang, and postdoctoral student Zhang Nanman contributed to this paper. M.S. student Ni Aoting, Ph.D. student Zhang Chenlu and postdoctoral fellow Nanxia Zhang are the co-first authors of this paper, and Associate Professor Feng Jie, Professor Chen Yadong, and Professor Lu Tao are the co-corresponding authors of this paper.
Bioorthogonal reactions have attracted much attention in the fields of organic chemistry, drug discovery, and chemical biology in recent years due to their high selectivity, safety, and efficiency without interfering with the living system, and have become an important tool to promote biomarker and precision therapy research. Although several novel bioorthogonal reactions have been reported, most of the current methods are still mainly based on tetrazine substrates or unsaturated hydrocarbon substrates, which are difficult to take into account the diversity of functional groups introduced, the adaptability of water-soluble substrates, and the broad-spectrum of the reaction system, and there is an urgent need for the development of new reaction systems to meet the demands of more complex applications in biological environments.
Design Ideas and Introduction to LBMR Reactions
In response to the above challenges, the research team innovatively developed a novel Light-Promoted Bioorthogonal Reaction via Molecular Recombination (LBMR). The reaction, in which isoxazole-3-carboxylate substrate and isoxazole-3-carboxylic acid or its salts are used as substrates, efficiently generates polysubstituted pyrrole derivatives in a biocompatible-like system. The reaction process involves light-induced molecular rearrangement and reorganization, and has the advantages of mild reaction conditions, fast kinetics, and no interference with active small molecules, demonstrating good substrate compatibility and biological system adaptability.
More importantly, the LBMR reaction product, 2-aminopyrrole, has natural fluorescence excitation properties, making the reaction directly applicable to cell imaging without the need to introduce additional fluorescent groups. This method has been successfully applied to the in situ fluorescent labeling of various tumor cells, such as A549, HUH-7, NUGC3, etc., which provides a simple and efficient new means for cell tracking and bio-imaging research.
In addition, the reaction system has also realized efficient in situ fluorescent labeling in zebrafish embryos, which further validates its potential for in vivo application and shows a broad prospect as a chemical biology tool.
In conclusion, the LBMR reaction utilizes a light-promoted molecular recombination strategy to achieve the rapid construction of tetrasubstituted pyrrole derivatives with a wide range of substrate adaptability, good biocompatibility, and in vitro and in vivo imaging capabilities, which provides a powerful complement to the existing bioorthogonal chemical reaction systems.
This work was supported by the National Natural Science Foundation of China and the “Double First Class” Construction Program of China Pharmaceutical University.
