Probing the Structure and Thermoresponsive Behavior of Multicompartment Micelles by Combined Solution‐ and Solid‐State NMR Spectroscopy

Multicompartment micelles (MCMs) that are formed from thermoresponsive triblock copolymers offer an interesting option for drug delivery systems. However, structural rearrangements are challenging to characterize. Here, we combine solution‐ and solid‐state NMR spectroscopy with complementary techniques (DLS, DSC, PXRD) to investigate two potentially MCM‐forming copolymers: methoxy poly(ethylene glycol)‐ block ‐poly(butyl acrylate)‐ block ‐poly‌‌(N‐‍isopropylacrylamide) (PBuAN250) and methoxy poly(ethylene glycol)‐ block ‐poly(benzyl acrylate)‐ block ‐poly(N‐isopropylacrylamide) (PBzAN300). P‐fraction values were extracted from variable‐temperature 1 H NMR to quantify the lower critical solution temperature (LCST) transition of poly(N‐isopropylacrylamide) (PNIPAM), revealing how core rigidity affects the transition. This was complemented by T 2 relaxation time data to further probe dynamics of chains upon rearrangement. Nuclear Overhauser effect spectroscopy (NOESY) was used to reveal spatial proximities between different polymer blocks. As PNIPAM becomes undetectable in solution above the LCST, solid‐state NMR was used to fill that gap. 1 H T 1 relaxation time measurements were employed on thermally treated freeze‐dried micelles to show convergence of PNIPAM and butyl acrylate (BuA) block relaxation times consistent with PNIPAM relocating into the hydrophobic core. 1 H‐ 13 C heteronuclear correlation (HETCOR) spectra further revealed subtle local changes in chain arrangements, overall demonstrating how comprehensive NMR characterization captures structure‐dynamics relationships and paints a consistent molecular‐level picture difficult to access with other methods.