Controlled radical release from iron oxide nanoparticles grafted with thermosensitive alkoxyamine triggered by external stimuli†

Abstract

We report an investigation of a controlled radical release produced by iron oxide nanoparticles (IONPs) of ca. 25 nm covalently grafted through phosphonic groups with a thermosensitive alkoxyamine, (6-(4-(1-((di-tert-butylamino)oxy)ethyl)benzamido)hexyl)phosphonate, having a relatively low homolysis temperature (k_d = 6.4 × 10⁻⁴ s⁻¹ at 77 °C, E_a = 117.8 kJ mol⁻¹). Action of an alternating current magnetic field (AMF) or light irradiation at 808 nm produces a rapid heating of the nanoparticles’ surface, which induces the homolysis of the C–ON bond of alkoxyamines facilitating the efficient formation of free radicals. We demonstrated based on homolysis kinetics investigated by electron paramagnetic resonance (EPR) spectroscopy that light irradiation at 808 nm (2.6 W cm⁻²) enables efficient radical release from grafted nanoparticles at 44 °C (t_1/2 = 23.6 min), whereas the free molecules required 20 h to show the same release at this temperature. AMF exposure accelerates the homolysis of alkoxyamine-grafted nanoparticles (16 kA m⁻¹, 2.9 mg mL⁻¹) twofold compared to the free alkoxyamine at 77 °C (t_1/2 = 7.9 min vs. 18 min). These findings underscore the critical importance of localized nanoscale effects, demonstrating that the homolysis rate on the nanoparticle surface under external stimuli is significantly higher compared to that under external solution heating, with this enhancement being even more pronounced under light irradiation.