Imaging Single-Chain Nanoparticle Folding via High-Resolution Mass Spectrometry.

Herein, we introduce the first approach to map single-chain nanoparticle (SCNP) folding via high-resolution electrospray ionization mass spectrometry (ESI MS) coupled with size exclusion chromatography. For the first time, the successful collapse of polymeric chains into SCNPs is imaged by characteristic mass changes, providing detailed mechanistic information regarding the folding mechanism. As SCNP system we employed methyl methacrylate (MMA) statistically copolymerized with glycidyl methacrylate (GMA), resulting in p(MMA-stat-GMA), subsequently collapsed by using B(C6F5)3 as catalyst. Both the precursor polymer and the SCNPs can be well ionized via ESI MS, and the strong covalent cross-links are stable during ionization. Our high-resolution mass spectrometric approach can unambiguously differentiate between two mechanistic modes of chain collapse for every chain constituting the SCNP sample.