Ultrasmall Nanogels from Intramolecular Cross-Linking of (Hyper)Branched Cyclic Polyglycerols with Diboronic Acids

We report the synthesis of ultrasmall nanogels (Rg < 6 nm) from branched and hyperbranched cyclic polyglycerols (Mn = 3–200 kg/mol) via intramolecular cross-linking with diboronic acids (benzene-1,4-diboronic acid, Bz-2B, and [(1,2-diphenylethene-1,2-diyl)bis(4,1-phenylene)] diboronic acid, TPE-2B) through dynamic covalent bonding. Structural analysis by small-angle X-ray scattering revealed a clear architecture–conformation relationship: high-molecular-weight hyperbranched cyclic polyglycerols formed compact, spherical structures, whereas low-molecular-weight branched analogues displayed open, fractal-like structures. Cross-linking preserved the overall size and conformation of the precursors, providing strong evidence of predominantly intramolecular nanogel formation with negligible aggregation, as indicated by the minimal low-Q scattering contribution. Incorporation of TPE-2B enabled fluorescence probing of nanogel structuring, revealing architecture-dependent localization of the fluorogen at the polymer periphery or within the interior. Enhanced emission arose from restricted intramolecular rotation of the phenyl rotors and was governed by the molecular weight of the polymer scaffold and the degree of fluorogen confinement. Nanogels formed with Bz-2B were able to physically entrap rhodamine B within their interstitial spaces, exhibiting a release behavior modulated by cross-linking density and molecular weight. These findings establish an architecture-dependent class of ultrasmall nanogels and demonstrate how dynamic covalent cross-linking, combined with fluorescence probing and scattering analysis, provides detailed insight into structure–property relationships in confined polymer nanostructures.