Fluorinated rotaxanes as sensitive 19F MRI agents: Threading for higher sensitivity

Abstract

As a promising imaging technology, the low sensitivity of fluorine-19 magnetic resonance imaging (19F MRI) severely hinders its biomedical applications. Herein, we have developed an unprecedented rotaxane-based strategy to improve the sensitivity of 19F MRI agents. By threading the fluorinated macrocycle into 2-blade pinwheel [2]rotaxanes, the 19F longitudinal relaxation rate R1 was dramatically increased, resulting in a significant 19F MRI signal intensity enhancement of up to 79%. Through comparative molecular dynamics studies using a series of solution and solid-state 1H/19F nuclear magnetic resonance (1H/19F NMR) and molecular dynamics simulations, it was found that the formation of mechanical bonds dramatically restricts the motion of the wheel fluorines and thus increasing the R1 for higher 19F MRI sensitivity. Besides a novel strategy for improving 19F MRI sensitivity, this study has established 19F NMR/MRI as a valuable technology for monitoring the molecular dynamics of rotaxanes, which may shed new light on high-performance 19F MRI agents and molecular devices.