‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

نویسندگان

چکیده

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in chemistry and biomedicine. CORMs kill bacteria culture animal models, but reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely commercially available CORM, displays numerous pharmacological, biochemical microbiological activities, generally attributed CO release. Here, we investigate basis of its potent antibacterial activity against Escherichia coli demonstrate, using three globin sensors, that releases negligible (<0.1 mol per CORM-2). A strong negative correlation between viability cellular ruthenium accumulation implies toxicity underlies biocidal activity. Exogenous amino acids thiols (especially cysteine, glutathione N-acetyl cysteine) protected inhibition growth by CORM-2. Bacteria treated with 30 ?M CORM-2, added cysteine histidine, exhibited no significant loss viability, were killed absence these acids. Their prevention correlates their CORM-2-binding affinities (Cys, Kd 3 ?M; His, 130 ?M) as determined 1H-NMR. Glutathione is proposed be an important intracellular target having much higher affinity for reduced (GSH) than oxidised (GSSG) (GSH, 2 GSSG, 25,000 ?M). The low, potent, levels (15 was accompanied cell lysis, judged release cytoplasmic ATP pools. effects related CORMs, design experiments, must re-examined light data.

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ژورنال

عنوان ژورنال: Antioxidants

سال: 2021

ISSN: ['2076-3921']

DOI: https://doi.org/10.3390/antiox10060915