Copper-doped metal-organic frameworks for the controlled generation of nitric oxide from endogenous S-nitrosothiols

Nitric oxide (NO) is an essential signaling molecule with a number of biological functions and holds great promise in biomedical applications. However, NO delivery technologies have been complicated due to the inherent properties of NO which include short half-life and limited transport distance in human tissues. In addition, the biofunctionality of NO is strongly dependent on its concentrations and locations where it is delivered. To achieve controlled NO delivery, many studies have focused on encapsulating NO donors into macromolecular scaffolds or using catalysts to realize in situ NO generation from NO prodrugs. Successful applications have been shown, however NO donor-loaded platforms experience the limitation of finite NO storage capacity. The present study reports the synthesis of a catalyst, copper-doped zeolitic imidazolate framework ZIF-8 (Cu²⁺/ZIF-8), that is designed to generate NO from naturally occurring endogenous NO donors. By tuning the copper doping percentages, we achieved controlled NO generation from S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). Cu²⁺/ZIF-8 particles retained their catalytic potency after 5 NO generation cycles and we showed that our copper-doped ZIF-8 catalyst produced a 10-fold increased amount of NO compared with previous reports. As a proof-of-concept study, we demonstrated the ability of copper-doped ZIF-8 to disperse bacterial biofilms in the presence of GSNO.