Issue 22, 2021

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

Abstract

Hydrogen sulfide (H2S) is an endogenous gasotransmitter with potential therapeutic value for treating a range of disorders, such as ischemia-reperfusion injury resulting from a myocardial infarction or stroke. However, the medicinal delivery of H2S is hindered by its corrosive and toxic nature. In addition, small molecule H2S donors often generate other reactive and sulfur-containing species upon H2S release, leading to unwanted side effects. Here, we demonstrate that H2S release from biocompatible porous solids, namely metal–organic frameworks (MOFs), is a promising alternative strategy for H2S delivery under physiologically relevant conditions. In particular, through gas adsorption measurements and density functional theory calculations we establish that H2S binds strongly and reversibly within the tetrahedral pockets of the fumaric acid-derived framework MOF-801 and the mesaconic acid-derived framework Zr-mes, as well as the new itaconic acid-derived framework CORN-MOF-2. These features make all three frameworks among the best materials identified to date for the capture, storage, and delivery of H2S. In addition, these frameworks are non-toxic to HeLa cells and capable of releasing H2S under aqueous conditions, as confirmed by fluorescence assays. Last, a cellular ischemia-reperfusion injury model using H9c2 rat cardiomyoblast cells corroborates that H2S-loaded MOF-801 is capable of mitigating hypoxia-reoxygenation injury, likely due to the release of H2S. Overall, our findings suggest that H2S-loaded MOFs represent a new family of easily-handled solid sources of H2S that merit further investigation as therapeutic agents. In addition, our findings add Zr-mes and CORN-MOF-2 to the growing lexicon of biocompatible MOFs suitable for drug delivery.

Graphical abstract: Biocompatible metal–organic frameworks for the storage and therapeutic delivery of hydrogen sulfide

Supplementary files

Article information

Article type
Edge Article
Submitted
03 Febr. 2021
Accepted
24 Apr. 2021
First published
30 Apr. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2021,12, 7848-7857

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

F. E. Chen, R. M. Mandel, J. J. Woods, J. Lee, J. Kim, J. H. Hsu, J. J. Fuentes-Rivera, J. J. Wilson and P. J. Milner, Chem. Sci., 2021, 12, 7848 DOI: 10.1039/D1SC00691F

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