Polymeric architecture as a tool for controlling the reactivity of palladium (II) loaded nanoreactors

Self-assembled systems, like polymeric micelles, have become great facilitators for conducting organic reactions in aqueous media due to their broad potential applications in green chemistry, as well as biomedical applications. Massive strides have been taken to improve the reaction scope of such systems to the point of performing multistep synthesis of active pharmaceutical ingredients using micelles. Considering these important advancements, we sought to study the relationships between the architecture of the amphiphiles and the reactivity of their PdII loaded micellar nanoreactors in conducting depropargylation. Towards this goal, we designed and synthesized a series of isomeric polyethylene glycol (PEG)-dendron amphiphiles with different dendritic architectures but with identical degree of hydrophobicity and hydrophilic to lipophilic balance (HLB). We observed that the dendritic architecture, which serves as the main binding site for the PdII ions, has greater influence on the reactivity than the hydrophobicity of the dendron. These trends remained constant for two different propargyl containing substrates, highlighting the robustness of the obtained results. Density functional theory (DFT) calculations of simplified models of the dendritic blocks revealed the different binding modes of the various dendritic architectures to PdII ions, which could explain the difference in the reactivity of the nanoreactors in this study. Our results show how tuning the internal architecture of amphiphiles and the resulting orientation of the chelating moieties can play a major role in controlling the reactivity of the nanoreactors.