A Mild and Efficient Approach to Functional Single-Chain Polymeric Nanoparticles via Photoinduced Diels–Alder Ligation

We present a new ambient temperature synthetic approach for the preparation of single-chain polymeric nanoparticles (SCNPs) under mild conditions using a UV-light-triggered Diels–Alder (DA) reaction for the intramolecular cross-linking of single polymer chains. Well-defined random copolymers with varying contents of styrene (S) and 4-chloromethylstyrene (CMS) were synthesized employing a nitroxide-mediated radical polymerization (NMP) initiator functionalized with a terminal alkyne moiety. Postpolymerization modification with 4-hydroxy-2,5-dimethylbenzophenone (DMBP) and an <i>N</i>-maleimide (Mal) derivative led to the functional linear precursor copolymers. The intramolecular cross-linking was performed by activating the DMBP groups via irradiation with UV light of 320 nm for 30 min in diluted solution (<i>c</i>_Polymer = 0.017 mg mL^–1). The ensuing DA reaction between the activated DMBP and the Mal groups resulted in well-defined single-chain polymeric nanoparticles. To control the size of the SCNPs, random copolymers with varying CMS contents (i.e., different functional group densities (FGD)) were employed for the single-chain collapse. Additionally, monotethered nanoparticles were prepared via the copper-catalyzed azide–alkyne cycloaddition between the alkyne bearing copolymer with the highest FGD and an azide-terminated poly­(ethylene glycol) (PEG) prior to UV-induced cross-linking. The formation of SCNPs was followed by size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and atomic force microscopy (AFM)