Investigations into the carbonic anhydrase inhibition of COS-releasing donor core motifs.

Carbonyl sulfide (COS) releasing scaffolds are gaining popularity as hydrogen sulfide (H2S) donors through exploitation of the carbonic anhydrase (CA)-mediated hydrolysis of COS to H2S. The majority of compounds in this emerging class of donors undergo triggerable decomposition (often referred to as self-immolation) to release COS, and a handful of different COS-releasing structures have been reported. One benefit of this donation strategy is that numerous caged COS-containing core motifs are possible and are poised for development into self-immolative COS/H2S donors. Because the intermediate release of COS en route to H2S donation requires CA, it is important that the COS donor motifs do not inhibit CA directly. In this work, we investigate the cytotoxicity and CA inhibition properties of different caged COS donor cores, as well as caged CO2 and CS2 motifs and non-self-immolative control compounds. None of the compounds investigated exhibited significant cytotoxicity or enhanced cell proliferation at concentrations up to 100 µM in A549 cells, but we identified four core structures that function as CA inhibitors, thus providing a roadmap for the future development of self-immolative COS/H2S donor motifs.

Spectroscopic investigation of the reaction of metallo-protoporphyrins with hydrogen sulfide.

Hydrogen sulfide (H2S) is the most recently discovered gasotransmitter molecule joining nitric oxide and carbon monoxide. In addition to being biologically important gases, these gasotransmitters also provide distinct modes of reactivity with biomimetic metal complexes. The majority of previous investigations on the reactivity of H2S with bioinorganic models have focused on Fe-based porphyrin systems, whereas investigations with other metals remains underinvestigated. To address this gap, we report here an examination of the reactions of H2S, HS-, and S8 with MgII, CuII, CoII, ZnII, CrII, SnIV, and MnII/III protoporphyrins.