Stability and compatibility of resorcin[4]arene hexamer cages with amphiphilic random copolymers in organic solvents.

The structural integrity and guest-hosting capabilities of resorcin[4]arene-based hexamer cages ([Rs4]6 and [Rs11]6) bearing different side chains (-C4H9, butyl or -C11H23, undecyl) is explored using water-soluble copolymers mapped in different solvents (CHCl3, CH2Cl2, toluene and THF). We here identify significant differences between the length of the macrocycle's "footing" chains (-C4H9 or -C11H23) and their intrinsic stability. NMR and DLS size analyses reveal that while both cages are stable in chloroform, the undecyl-footed [Rs11]6 cage demonstrates superior intrinsic stability in toluene and dichloromethane, self-assembling into discrete hexamers (D h = 3.6 nm) even in the absence of embedded guests. In contrast, the butyl-footed [Rs4]6 cage requires an alkylammonium salt template to avoid formation of large and unstable aggregates. When mixed with amphiphilic random copolymers, the cage [Rs11]6 maintains high encapsulation efficiencies at molar ratios of up to 1 : 6 (cage : copolymer), regardless of the copolymer's philicity, displaying either aliphatic or fluorinated sidechains. A competitive interaction between the copolymers' polyethylene glycol (PEG) side chains and structural water molecules is proposed, establishing the cage [Rs11]6 as a robust and versatile scaffold for the development of complex, water-soluble nano-assemblies. This now offers a resilient platform for biomimetic carrier and catalytic applications.