Janus-Type Dendrimers Based on Highly Branched Fluorinated Chains with Tunable Self-Assembly and ¹⁹F Nuclear Magnetic Resonance Properties

Tuning the self-assembly of dendritic amphiphiles represents a major challenge for the design of advanced nanomaterials for biomimetic applications. The morphology of the final aggregates, in fact, critically depends on the primary structure of the dendritic building blocks as well as the environmental conditions. Here we report a new family of fluorinated Janus-type dendrimers (FJDs), based on a short-chain and branched fluorinated synthon with 27 magnetically equivalent fluorine atoms, linked to bis-MPA polyester dendrons of different generations. Increasing size, flexibility, and number of peripheral hydroxyl groups, we observed a peculiar self-assembly behavior in bulk and in aqueous media as a consequence of the subtle balance between their fluorinated and hydrophilic portions. The lowest generation FJDs formed spherical nanoparticles in water, e.g., micelles, showing a single 19F NMR peak with good signal-to-noise ratio and over time stability, making them promising as 19F-MRI traceable probes. The highest generation FJD, instead, presented an interesting morphological transition from multilamellar dendrimersomes to tubules as a consequence of a subtle balance of intra- and intermolecular forces that compete at the interface. Interestingly, a reduction of the local mobility of CF3 groups passing from dendrimersomes to tubules switches off the 19F NMR signal. The transition mechanism has been rationalized by coarse-grain simulations as well as demonstrated by using cosolvents of different nature (e.g., fluorinated) that promote conformational changes, ultimately reflected in the self-assembly behavior. Short and branched fluorinated chains have here been demonstrated as new moieties for the design of FJDs with tunable self-assembly behavior for potential applications as biocompatible 19F MRI probes in the construction of theranostic platforms.