In the middle of the meeting, Professor Lu Hua's team in the School of Chemistry and Molecular Engineering of Peking University recently published an important discovery in the National Science Review - in the process of studying proline N-carboxylic acid endoic anhydride (ProNCA) ring-opening polymerization (ROP), compared with the traditional drying chamber environment, the team found its ultra-fast controllable polymerization reaction process in aqueous solution.
Screenshots of web pages
ProNCA monomers are hydrolyzable and the solubility of the hydrolysate product polyproline (PLP) in organic solvents is very low. Due to this dilemma, the ring-opening polymerization reaction of proline N-carboxylic acid anhydride often requires up to a week in a dried organic solvent, and the molecular weight and dispersibility of the product are almost uncontrollable. This new method solves this problem, just replace the anhydrous organic solvent with a water-acetonitrile mixed solvent, and the polymerization reaction can be completed in just 30 seconds, and the polymerization degree of 20 oligoproline is obtained, or the polymerization degree of 200 oligoproline is obtained within 5 minutes.
Schematic diagram of the reaction | References[1]
Since the polymerization rate of the reaction is extremely fast, far exceeding the rate of side reactions such as monomer hydrolysis, ROP has high controllability, showing high group fidelity, chain growth kinetic mode, predictable molecular weight, small dispersibility, and wide range of application of initiators. Mechanical experiments and density functional theory (DFT) calculations show that water molecules play the role of proton carriers during the polymerization process, which helps to transfer protons in the rate control step, thereby reducing the reaction energy barrier of up to 7.1kcal/mol and greatly accelerating the polymerization reaction process.
Water molecules play the role of proton carriers in the polymerization process | Flickr, Allan Foster / CC BY-NC-ND 2.0（https://creativecommons.org/licenses/by-nc-nd/2.0/）
Because the reaction conditions are mild, simple to operate, and easy to purify, the researchers also synthesized asparaginase-polyproline conjugates using the anti-cancer drug asparaginase as a initiator. The researchers found that asparaginase-polyproline conjugates significantly prolonged the blood circulation time of asparaginase compared to natural drug proteins, improved anti-tumor effects in vivo, and reduced immunogenicity.
Next, Professor Lu will continue to collaborate with the team of Professor Song Yuqin of Peking University Cancer Hospital to do more in-depth preclinical research and strive to benefit patients with acute lymphoid leukemia and NK/T cell lymphoma. In addition, Professor Lu believes that polyproline itself has a wide range of potential uses in the food industry, cosmetics and many other material applications.
bibliography
[1] Yali Hu, Zi-You Tian, Wei Xiong, Dedao Wang, Ruichi Zhao, Yan Xie, Yu-Qin Song, Jun Zhu, Hua Lu, Water-Assisted and Protein-Initiated Fast and Controlled Ring-Opening Polymerization of Proline N-Carboxyanhydride, National Science Review, 2022;, nwac033, https://doi.org/10.1093/nsr/nwac033
[2] https://phys.org/news/2022-04-unexpected-ultrafast-synthesis-collagen-like-synthetic.html
Compiler: Yin Chen
Edit: Four seven
Typography: Yin Ningliu
Image source: Flickr
Research team
Corresponding author Lu Hua: Graduated from the School of Chemistry and Molecular Engineering of Peking University, and received his Ph.D. from the Department of Materials Science at the University of Illinois at Urbana-Champaign. He is currently a professor at the School of Chemistry and Molecular Engineering at Peking University, a doctoral supervisor, and an associate editor of biomacromolecules, a journal of the American Chemical Society. His research interests include polymer chemistry, biodegradable biomedical polymer materials, biocoupling and biomedical engineering.
Https://www.chem.pku.edu.cn/luhua/ of the research group website
Thesis information
Published in the National Science Review
Published on February 24, 2022
论文标题Water-Assisted and Protein-Initiated Fast and Controlled Ring-Opening Polymerization of Proline N-Carboxyanhydride（ DOI：10.1093/nsr/nwac033）