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

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