Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with untapped potential as a therapeutic in the treatment of various diseases and disorders, such as Parkinson's disease, inflammation, cancer, and ischemia-reperfusion injury. Due to the inherent dangers of working directly with this toxic, flammable, corrosive gas, research in the area of therapeutic H2S delivery has traditionally been limited to the design of small molecule H2S donors. However, these H2S donor molecules often generate unwanted reactive side products in addition to the gas, leading to undesirable side effects. Here, we demonstrate that H2S release from metal-organic frameworks (MOFs) is a more promising alternative for controlled delivery of gaseous H2S under physiological conditions. In particular, we evaluate the stability of a range of MOFs toward H2S and determine their cytotoxicity toward HeLa cells. From gas adsorption measurements and powder X-ray diffraction studies we demonstrate that H2S binds strongly and reversibly in these MOFs and can be quantifiably delivered in solution with a kinetics assay monitored via gas chromatography. Last, we demonstrate that the surface of these MOFs can be functionalized with various biocompatible coatings enabling controlled, targeted H2S delivery. From our findings, we conclude that H2S-loaded MOFs are easily accessible, solid-state sources of H2S, enabling safe storage and delivery of the gas for use as a therapeutic agent.

Surface functionalization of biocompatible metal-organic frameworks for the storage and therapeutic delivery of hydrogen sulfide

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.