Micellar “Click” Nanoreactors: Spiking\nPluronic-Based Micelles with Polymeric Ligands

In recent years,\nthe development of nanoreactors, such as micellar\nnanoreactors (MNRs) for catalytic transformations, has gained significant\nattention due to their potential in enhancing reaction rates, selectivity,\nefficiency, and, as importantly, the ability to conduct organic chemistry\nin aqueous solutions. Among these, the copper(I)-catalyzed azide–alkyne\ncycloaddition (CuAAC) reaction represents a pivotal transformation\nand is widely used in the synthesis of bioconjugates, pharmaceuticals,\nand advanced materials. This study aims toward advancing our understanding\nof the design and utilization of polymeric amphiphiles containing\ntris-triazole ligands as an integral element for CuAAC reactions within\nMNRs. Specifically, our investigation delves into three critical factors\nthat influence the reaction rate within MNRs: hydrophobicity, architectural\nconfiguration of the polymeric ligands, and their concentration. Utilizing\nthe high molecular precision of dendritic amphiphiles, we synthesized\npolymeric ligands with two distinct architectures, namely, PEG-ditris-triazole\namphiphile (DTA) and PEG-monotris-triazole amphiphile (MTA), and explored\ntheir CuAAC reactivity through coassembly with commercially available\nPluronic P123 amphiphiles. The results indicate that the architecture\nand the concentration of the polymeric ligands play more dominant\nroles in influencing the reaction rate than the hydrophobicity of\nthe dendritic blocks. Notably, while MNRs assembled from solely DTA\nshowed a dampened reaction rate, spiking P123 micelles with DTA yielded\nan MNR with significantly faster rates. Moreover, P123 MNRs spiked\nwith the synthesized MTA demonstrated increased CuAAC reaction rates\ncompared to those spiked with the DTA, and they even outperformed\nthe widely used Tris(benzyltriazolylmethyl)amine ligand. These findings\nprovide valuable insights into the design principles of polymer-based\nligands for constructing reactive MNRs and other types of nanoreactors\nfor efficient catalytic transformations.