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A Dinuclear Persulfide-Bridged Ruthenium Compound is a Hypoxia-Selective Hydrogen Sulfide (H₂ S) Donor.

ABSTRACT: Hydrogen sulfide (H₂ S) is a gaseous molecule that has received attention for its role in biological processes and therapeutic potential in diseases, such as ischemic reperfusion injury. Despite its clinical relevance, delivery of H₂ S to biological systems is hampered by its toxicity at high concentrations. Herein, we report the first metal-based H₂ S donor that delivers this gas selectively to hypoxic cells. We further show that H₂ S release from this compound protects H9c2 rat cardiomyoblasts from an in vitro model of ischemic reperfusion injury. These results validate the utility of redox-activated metal complexes as hypoxia-selective H₂ S-releasing agents for use as tools to study the role of this gaseous molecule in complex biological systems.

SUBMITTER: Woods JJ

PROVIDER: S-EPMC7855780 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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A Dinuclear Persulfide-Bridged Ruthenium Compound is a Hypoxia-Selective Hydrogen Sulfide (H2 S) Donor.

Woods Joshua J JJ Wilson Justin J JJ

Angewandte Chemie (International ed. in English) 20201116 3

Hydrogen sulfide (H2 S) is a gaseous molecule that has received attention for its role in biological processes and therapeutic potential in diseases, such as ischemic reperfusion injury. Despite its clinical relevance, delivery of H2 S to biological systems is hampered by its toxicity at high concentrations. Herein, we report the first metal-based H2 S donor that delivers this gas selectively to hypoxic cells. We further show that H2 S release from thi ...[more]

PMID: 33022823

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Project description:The antibacterial activity of 22 thiolato-bridged dinuclear ruthenium(II)-arene compounds was assessed in vitro against Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus. None of the compounds efficiently inhibited the growth of the three E. coli strains tested, and only compound 5 exhibited a medium activity against this bacterium [MIC (minimum inhibitory concentration) of 25 µM]. However, a significant antibacterial activity was observed against S. pneumoniae, with MIC values ranging from 1.3 to 2.6 µM for compounds 1-3, 5, and 6. Similarly, compounds 2, 5-7, and 20-22 had MIC values ranging from 2.5 to 5 µM against S. aureus. The tested diruthenium compounds have a bactericidal effect significantly faster than that of penicillin. Fluorescence microscopy assays performed on S. aureus using the BODIPY-tagged diruthenium complex 15 showed that this type of metal compound enters the bacteria and does not accumulate in the cell wall of gram-positive bacteria. Cellular internalization was further confirmed by inductively coupled plasma mass spectrometry experiments. The nature of the substituents anchored on the bridging thiols and the compounds molecular weight appears to significantly influence the antibacterial activity. Thus, if overall a decrease of the bactericidal effect with the increase of compounds' molecular weight is observed, however, the complexes bearing larger benzo-fused lactam substituents had low MIC values. This first antibacterial activity screening demonstrated that the thiolato-diruthenium compounds exhibit promising activity against S. aureus and S. pneumoniae and deserve to be considered for further studies. IMPORTANCE The in vitro assessment of diruthenium(II)-arene compounds against Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus showed a significant antibacterial activity of some compounds against S. pneumoniae, with minimum inhibitory concentration (MIC) values ranging from 1.3 to 2.6 µM, and a medium activity against E. coli, with MIC of 25 µM. The nature of the substituents anchored on the bridging thiols and the compounds molecular weight appear to significantly influence the antibacterial activity. Fluorescence microscopy showed that these ruthenium compounds enter the bacteria and do not accumulate in the cell wall of gram-positive bacteria. These diruthenium(II)-arene compounds exhibit promising activity against S. aureus and S. pneumoniae and deserve to be considered for further studies, especially the compounds bearing larger benzo-fused lactam substituents.

Dataset Information

A Dinuclear Persulfide-Bridged Ruthenium Compound is a Hypoxia-Selective Hydrogen Sulfide (H₂ S) Donor.

Publications

A Dinuclear Persulfide-Bridged Ruthenium Compound is a Hypoxia-Selective Hydrogen Sulfide (H<sub>2</sub> S) Donor.

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