Three-Dimensional Hydrazone-Functionalized Covalent Organic Frameworks as pH-Triggered Rotary Switches

The property expansion of three-dimensional (3D) functionalized covalent organic frameworks (COFs) is important for developing their potential applications. Herein, we report the first case of 3D hydrazone-decorated COFs as pH-triggered molecular switches, and explore their application in the stimuli-responsive drug delivery system. These functionalized COFs with hydrazone groups on the channel walls were obtained via a multi-component bottom-up synthesis strategy. They exhibit a reversible E/Z isomerization at various pH values, confirmed by UV-vis absorption spectroscopy and proton conduction. Remarkably, after loading cytarabine (Ara-C) as a model drug molecule, these pH-responsive COFs showed an excellent and intelligent sustained-release effect with an almost 4-fold increase in the Ara-C release at pH = 4.8 than at pH = 7.4, which will effectively improve drug-targeting and reduce drug side effects. Thus, these results open a way toward designing 3D stimuli-responsive functionalized COF materials and promote their potential application as drug carriers in the field of disease treatment.