Investigating the generation of hydrogen sulfide from the phosphonamidodithioate slow-release donor GYY4137Electronic supplementary information (ESI) available: (i) Experimental procedures and characterisation data for the hydrolysis pathway and compounds prepared. (ii) Experimental procedures for cell culture, H2S generation, cytotoxicity assays and LPS treatment of RAW264.7 cells. CCDC 1053548. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5md00170f

• Main Authors: Alexander, Benjamin E, Coles, Simon J, Fox, Bridget C, Khan, Tahmina F, Maliszewski, Joseph, Perry, Alexis, Pitak, Mateusz B, Whiteman, Matthew, Wood, Mark E
• Format: Journal Article
• Language: English
• Published: 02.09.2015
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c5md00170f

A combination of NMR spectroscopy, mass spectrometry and chemical synthesis was used to elucidate the two-step hydrolytic decomposition pathway of the slow-release hydrogen sulfide (H 2 S) donor GYY4137 and the key decomposition product was also prepared by an independent synthetic route. The (dichloromethane-free) sodium salt of the phosphonamidodithioate GYY4137 was also produced as a pharmaceutically more acceptable salt. In contrast with GYY4137 and its sodium salt, the decomposition product did not generate H 2 S or exert cytoprotective or anti-inflammatory effects in oxidatively stressed human Jurkat T-cells and LPS-treated murine RAW264.7 macrophages. The decomposition product represents a useful control compound for determining the biological and pharmacological effects of H 2 S generated from GYY4137. A two-step hydrolytic decomposition pathway has been elucidated for the slow-release hydrogen sulfide donor GYY4137.