Water aids in the surprising and rapid synthesis of collagen-like synthetic poly-L-proline.

A team led by Prof. Hua Lu from Peking University’s College of Chemistry and Molecular Engineering announced a startling finding in a paper published recently online in the National Science Review. The scientists discovered rapid and controlled polymerization in aqueous solutions while examining the ROP of ProNCA, a sort of reaction that would traditionally have been performed in a dry box.

The ProNCA monomer is highly hydrolyzable, while the resultant PLP is very poorly soluble in organic solvents. Because of this conundrum, the ROP of ProNCA in dry organic solvents often took up to a week, giving oligomers with little control over molecular weight and dispersion. The novel approach simply replaces the anhydrous organic solvent with a mixed water-acetonitrile solvent, and the polymerization reaction can be finished in 30 seconds to generate an oligoproline with a degree of polymerization (DP) of 20, or a PLP with a DP of up to 200 in 5 minutes.

Because the polymerization rate is exceedingly fast, greatly exceeding the rate of side reactions such as monomer hydrolysis, the ROP is well regulated, as evidenced by high end group fidelity, chain growth kinetic pattern, predictable molecular weight, narrow dispersion, and broad initiator scope. Mechanistic experiments and density functional theory (DFT) calculations suggest that water acts as a proton shuttle during polymerization, assisting proton transfer in the rate-determining step and lowering the reaction energy barrier by up to 7.1 kcal/mol, dramatically accelerating polymerization.

The researchers also generated asparaginase-PLP conjugates utilizing asparaginase, an anticancer medication, as an initiator due to the mild reaction conditions, simple operation, and ease of purification. In collaboration with Professor Song Yuqin’s team from Peking University Cancer Hospital, the researchers discovered that the asparaginase-PLP conjugate can significantly prolong the blood circulation time of asparaginase, improve antitumor efficacy in vivo, and reduce immunogenicity when compared to the wild-type drug protein. The two research teams are eager to work further to perform more in-depth preclinical research in the future, with the goal of benefiting patients with acute lymphoblastic leukemia and NK/T cell lymphoma. Prof. Lu also feels that PLP has the potential to be useful in the food industry, cosmetics, and a variety of other material uses.

ProNCA’s real-time ROP When the researchers introduced the initiator solution to the dissolved monomers in a mixed water-acetonitrile solvent, the polymerization reaction started promptly and emitted a substantial amount of carbon dioxide, and the reaction was finished in one minute. Scientific China Press is credited.

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