Fluorinated [2]rotaxanes as sensitive19 F MRI agents: Threading for higher sensitivity

As a promising imaging technology, the low sensitivity of fluorine-19 magnetic resonance imaging (19 F MRI) severely hinders its biomedical applications. Herein, we have developed an unprecedented rotaxane- based strategy to improve the sensitivity of19 F MRI agents. By threading the fluorinated macrocycle into 2-blade pinwheel [2]rotaxanes, the19 F longitudinal relaxation rate R1 was dramatically increased, result- ing in a significant19 F MRI signal intensity enhancement of up to 79%. Through comparative molecular dynamics studies using a series of solution and solid-state1 H/19 F nuclear magnetic resonance (1 H/19 F NMR) and molecular dynamics simulations, it was found that the formation of mechanical bonds dramat- ically restricts the motion of the wheel fluorines and thus increasing the R1 for higher19 F MRI sensitivity. Besides a novel strategy for improving19 F MRI sensitivity, this study has established19 F NMR/MRI as a valuable technology for monitoring the molecular dynamics of rotaxanes, which may shed new light on high-performance19 F MRI agents and molecular devices.