Comparison of thermoresponsive Diels-Alder linkers for the release of payloads from magnetic nanoparticles via hysteretic heating

Abstract

Investigation into the use of thermally reversible Diels-Alder chemistry coupled with magnetic iron oxide nanoparticles has grown over the last decade. This technology has been used for a variety of applications such as thermoresponsive materials, catalytic chemistry, and drug delivery systems. In this study, we evaluate two distinct thermally labile Diels-Alder linkers for the release of payloads from the surface of magnetic iron oxide nanoparticles. Density functional theory (DFT) computational predictions of the Gibbs free energy and enthalpy reaction barriers were performed and revealed a dramatic difference in reverse energy barriers between the two linkers. These thiophene-based cycloadducts were then synthesized, conjugated to the surface of iron oxide nanoparticles, and characterized by NMR and ESI-MS. The results of the modeling were confirmed when the functionalized nanoparticles were subjected to immersion heating and the payload release rates observed were in agreement with the DFT calculations. Similarly, AMF-RF hysteretic heating of the functionalized nanoparticles revealed payload release rates that correlated with the DFT calculations and the data from the heat immersion studies. Together, these results indicate that these distinct thermally labile Diels-Alder linkers can be used to fine-tune the kinetics of payload release from nanoparticles.

Keywords

• Diels-alder
• Click chemistry
• Alternating magnetic field
• Controlled release
• Iron oxide
• Magnetic nanoparticles