title: Therapeutic Delivery of H2S via COS: Small Molecule and Polymeric Donors with Benign Byproducts.
abstract: Carbonyl sulfide (COS) is a gas that may play important roles in mammalian and bacterial biology, but its study is limited by a lack of suitable donor molecules. We report here the use of N-thiocarboxyanhydrides (NTAs) as COS donors that release the gas in a sustained manner under biologically relevant conditions with innocuous peptide byproducts. Carbonic anhydrase converts COS into H2S, allowing NTAs to serve as either COS or H2S donors, depending on the availability of the enzyme. Analysis of the pseudo-first-order H2S release rate under biologically relevant conditions revealed a release half-life of 75 min for the small molecule NTA under investigation. A polynorbornene bearing pendant NTAs made by ring-opening metathesis polymerization was also synthesized to generate a polymeric COS/H2S donor. A half-life of 280 min was measured for the polymeric donor. Endothelial cell proliferation studies revealed an enhanced rate of proliferation for cells treated with the NTA over untreated controls.
authors.affiliation: Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.|Macromolecules Innovation Institute, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Chadwick R
authors.initials: CR
authors.lastname: Powell
authors.affiliation: Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.|Macromolecules Innovation Institute, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Foster
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine , Duck Pond Drive, Blacksburg, Virginia 24061, United States.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Okyere
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine , Duck Pond Drive, Blacksburg, Virginia 24061, United States.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Theus
authors.affiliation: Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.|Macromolecules Innovation Institute, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: John B
authors.initials: JB
authors.lastname: Matson
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D055772:Green Chemistry Technology; D006834:Hydrazines / Q000737:chemistry; D006862:Hydrogen Sulfide / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013461:Sulfur Oxides / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D006834:Hydrazines; D011108:Polymers; D013461:Sulfur Oxides; C011368:thiocarbohydrazide; C010063:carbonyl sulfide; D006862:Hydrogen Sulfide