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

Abstract

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 (Dh = 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.