SPION nanoparticles for delivery of dopaminergic isoquinoline and benzazepine derivatives

Abstract

Superparamagnetic iron nanoparticles (SPIONs) have become one of the most useful colloidal systems in nanomedicine. We report here the preparation of new hybrid core@shell systems based on SPION nanoparticles coated with a SiO₂ shell (SPION@SiO₂) and functionalized with carboxyl groups (SPION@SiO₂-COOH). A series of new N-alkylamino- and N-alkylamido-terminated 1-phenyl- tetrahydroisoquinolines (THIQs) and 3-tetrahydrobenzazepines (THBs) derivatives presenting -SMe and -Cl groups, respectively, with potential dopaminergic activity, are synthesized and incorporated to the hybrid system. We include the synthetic details for THIQs and THBs derivatives preparation and investigate the influence of the terminal-functional group as well as the number of carbon atoms linked to THIQ and THB molecules during the coupling to the SPION@SiO₂-COOH. Nuclear magnetic resonance (NMR) and electron ionization mass spectrometry (EI-MS) are used to characterize the synthesized THIQs and THBs. High-angle annular dark-field transmission electron microscopy (HAADF-TEM), energy dispersive X-ray transmission electron microscopy (EDX-TEM), and proton high-resolution magic angle spinning NMR spectroscopy¹H HRMAS-NMR) are used to confirm the presence of THB and THIQ molecules onto the surface of the nanoparticles. The hybrid SPION@SiO₂-THIQ and THB systems show significant activity toward the D₂ receptor, reaching Ki values of about 20 nM, thus having potential application in the treatment of central nervous system (CNS) diseases.

Keywords: Benzazepine; Dopamine receptors; Dopaminergic activity; Isoquinoline; SPIONs; SiO(2) shell; Surface functionalization.