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

Abstract

Hydrogen sulfide (H 2 S) 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, H 2 S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H 2 S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H 2 S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H 2 S release from metal−organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H 2 S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg 2 (dobdc) (dobdc 4− = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H 2 S delivery due to its strong yet reversible binding of H 2 S, 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 H 2 S-dosed Mg 2 (dobdc) supports that the high H 2 S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H 2 S from Mg 2 (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 H 2 S gas. Overall, H 2 S-loaded Mg 2 (dobdc) is an easily accessible, solid-state source of H 2 S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.