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 (<b>R</b><sub><b>F</b></sub>), one contains achiral hydrogenated dendrons (<b>R</b><sub><b>H</b></sub>), while one denoted hybrid Janus dendrimer, contains a combination of chiral-racemic fluorinated and achiral hydrogenated dendrons (<b>R</b><sub><b>HF</b></sub>) in its hydrophobic part. Two Janus dendrimers contain either chiral-racemic fluorinated dendrons and a green fluorescent dye conjugated to its hydrophilic part (<b>R</b><sub><b>F</b></sub><b>-NBD</b>) or achiral hydrogenated and a red fluorescent dye in its hydrophilic part (<b>R</b><sub><b>H</b></sub><b>-RhB</b>). These <b>R</b><sub><b>F</b></sub>, <b>R</b><sub><b>H</b></sub>, and <b>R</b><sub><b>H</b>F</sub> 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 <b>R</b><sub><b>F</b></sub> and <b>R</b><sub><b>H</b></sub> dendrons are not miscible, <b>R</b><sub><b>F</b></sub><b>-NBD</b> and <b>R</b><sub><b>H</b></sub><b>-RhB</b> were employed to investigate by fluorescence microscopy the self-sorting and coassembly of <b>R</b><sub><b>F</b></sub> and <b>R</b><sub><b>H</b></sub> as well as of phospholipids into hybrid DSs mediated by the hybrid hydrogenated-fluorinated <b>R</b><sub><b>HF</b></sub> Janus dendrimer. The hybrid <b>R</b><sub><b>HF</b></sub> Janus dendrimer coassembled with both <b>R</b><sub><b>F</b></sub> and <b>R</b><sub><b>H</b></sub>. Three-component hybrid DSs containing <b>R</b><sub><b>H</b></sub>, <b>R</b><sub><b>F</b></sub>, and <b>R</b><sub><b>HF</b></sub> were formed when the proportion of <b>R</b><sub><b>HF</b></sub> was higher than 40%. With low concentration of <b>R</b><sub><b>HF</b></sub> and in its absence, <b>R</b><sub><b>H</b></sub> and <b>R</b><sub><b>F</b></sub> self-sorted into individual <b>R</b><sub><b>H</b></sub> or <b>R</b><sub><b>F</b></sub> DSs. Phospholipids were also coassembled with hybrid <b>R</b><sub><b>HF</b></sub> 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 <sup>19</sup>F-MRI make them important tools for synthetic biology.