Biocompatible metal-organic frameworks for the storage and therapeutic delivery of hydrogen sulfide

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter with untapped potential as a therapeutic in the treatment of various diseases and disorders, such as ischemia-reperfusion injury as a result of myocardial infarction or stroke. Due to its highly toxic and corrosive nature, delivery of the gas in a medicinal setting has traditionally been difficult and dangerous. Current small molecule H₂S donors being investigated for their therapeutic potential often generate unwanted sulfur-containing and/or reactive side products in addition to the gas, leading to undesirable side effects. Here, we demonstrate that H₂S release from biocompatible metal-organic frameworks (MOFs) is a more promising alternative for H₂S delivery under physiological conditions. The three frameworks presented herein, namely the fumaric acid-based MOF-801, mesaconic acid-based Zr-mes, and the new itaconic acid-based CORN-MOF-2, exhibit strong, reversible binding of H₂S as determined from gas adsorption measurements and density functional theory calculations. In addition, these sustainably-derived, biocompatible frameworks are non-toxic to HeLa cells and release H₂S in aqueous media via fluorescence monitoring using the probe 1,5-dansyl azide. Last, we demonstrate that H₂S-loaded MOF-801 is capable of alleviating reperfusion injury in H9c2 rat cardiomyoblast cells with an ischemia-reperfusion injury model. 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.