Transdermal Hydrogen Sulfide Delivery Enabled by Open-Metal-Site Metal–Organic Frameworks

Abstract

Hydrogen sulfide (H₂S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, H₂S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H₂S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H₂S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H₂S release from metal–organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H₂S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg₂(dobdc) (dobdc^4– = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H₂S delivery due to its strong yet reversible binding of H₂S, high capacity (14.7 mmol/g at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H₂S-dosed Mg₂(dobdc) supports that the high H₂S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H₂S from Mg₂(dobdc) is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide but this represents the first example of controlled transdermal delivery of pure H₂S gas. Overall, H₂S-loaded Mg₂(dobdc) is an easily accessible, solid-state source of H₂S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.