Micellar "Click" Nanoreactors: Spiking Pluronic-Based Micelles with Polymeric Ligands

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