Mandel, Ruth M. Lotlikar, Piyusha S. Runcevski, Tomce Lee, Jung-Hoon Woods, Joshua J. Pitt, Tristan A. Wilson, Justin J. Milner, Phillip J. 2024-07-18T06:00:17Z 2024-07-18T06:00:17Z 2024-07-18 2024-07 0002-7863 https://pubs.kist.re.kr/handle/201004/150260 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 Mg-2(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 degrees C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H2S-dosed Mg-2(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 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 H2S gas. Overall, H2S-loaded Mg-2(dobdc) is an easily accessible, solid-state source of H2S, enabling safe storage and transdermal delivery of this therapeutically relevant gas. English American Chemical Society Transdermal Hydrogen Sulfide Delivery Enabled by Open-Metal-Site Metal-Organic Frameworks Article 10.1021/jacs.4c00674 1 Journal of the American Chemical Society, v.146, no.28, pp.18927 - 18937 Journal of the American Chemical Society 146 28 18927 18937 N scie scopus 001265707000001 2-s2.0-85198152865 Chemistry, Multidisciplinary Chemistry Article PROMOTES CELL-PROLIFERATION HIGHLY TOXIC H2S MAGNESIUM THIOLATE ADSORPTION GASOTRANSMITTER CHEMISTRY DONOR MN NI CO