Molecular‐Level Interactions of Nanodisc‐Forming Copolymers Dissected by EPR Spectroscopy

Abstract

AbstractThis study focuses on analyzing the noncovalent interaction patterns between three lipid‐nanodisc‐forming polymers and nitroxide radicals which are used as small organic tracer molecules. Besides the negatively charged polymers diisobutylene/maleic acid (DIBMA) and styrene/maleic acid (SMA) (2:1), the solvation behavior of a newly synthesized zwitterionic styrene/maleic amide sulfobetaine copolymer named SMA‐sulfobetaine (SB) is characterized. The applied spin probes vary in their respective chemical structure, allowing the report of different local micropolarities and nanoscopic regions by recording temperature‐dependent continuous‐wave electron paramagnetic resonance (CW EPR) spectra. In combination with light scattering experiments, a nanoscopic interpretation of the dominant polymer/guest molecule interaction patterns is provided. The results indicate that in SMA and DIBMA, ionic interactions dominate the interaction patterns with other molecules. In SMA‐SB, the zwitterionic side chains mainly induce a dynamic assembly with guest molecules due to weaker noncovalent interactions. Depending on the applied spin probe, temperature‐dependent CW EPR measurements reveal nanoscopic cloud points depending on the interaction patterns with SMA‐SB which can occur more than 20 °C below its macroscopically observed upper critical solution temperature. Finally, the detailed dissection of interaction patterns may provide a better understanding that may even allow tuning the polymers’ properties for use in lipid nanodisc formation.