Self-Sorting and Coassembly of Fluorinated, Hydrogenated, and Hybrid Janus Dendrimers into Dendrimersomes

The modular synthesis of a library containing seven self-assembling amphiphilic Janus dendrimers is reported. Three of these molecules contain environmentally friendly chiral-racemic fluorinated dendrons in their hydrophobic part (R_F), one contains achiral hydrogenated dendrons (R_H), while one denoted hybrid Janus dendrimer, contains a combination of chiral-racemic fluorinated and achiral hydrogenated dendrons (R_HF) in its hydrophobic part. Two Janus dendrimers contain either chiral-racemic fluorinated dendrons and a green fluorescent dye conjugated to its hydrophilic part (R_F-NBD) or achiral hydrogenated and a red fluorescent dye in its hydrophilic part (R_H-RhB). These R_F, R_H, and R_HF Janus dendrimers self-assembled into unilamellar or onion-like soft vesicular dendrimersomes (DSs), with similar thicknesses to biological membranes by simple injection from ethanol solution into water or buffer. Since R_F and R_H dendrons are not miscible, R_F-NBD and R_H-RhB were employed to investigate by fluorescence microscopy the self-sorting and coassembly of R_F and R_H as well as of phospholipids into hybrid DSs mediated by the hybrid hydrogenated-fluorinated R_HF Janus dendrimer. The hybrid R_HF Janus dendrimer coassembled with both R_F and R_H. Three-component hybrid DSs containing R_H, R_F, and R_HF were formed when the proportion of R_HF was higher than 40%. With low concentration of R_HF and in its absence, R_H and R_F self-sorted into individual R_H or R_F DSs. Phospholipids were also coassembled with hybrid R_HF Janus dendrimers. The simple synthesis and self-assembly of DSs and hybrid DSs, their similar thickness with biological membranes and their imaging by fluorescence and ¹⁹F-MRI make them important tools for synthetic biology.