In Vitro Characterization of a Threonine-Ligated Molybdenyl-Sulfide Cluster as a Putative Cyanide Poisoning Antidote: Intracellular Distribution, Effects on Organic Osmolyte Homeostasis, and Induction of Cell Death

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Binuclear molybdenum sulfur complexes are effective for the catalytic conversion of cyanide into thiocyanate. The complexes themselves exhibit low toxicity and high aqueous solubility, which render them suitable as antidotes for cyanide poisoning. The binuclear molybdenum sulfur complex [(thr)Mo2O2(μ-S)2(S2)]- (thr - threonine) was subjected to biological studies to evaluate its cellular accumulation and mechanism of action. The cellular uptake and intracellular distribution in human alveolar (A549) cells, quantified by inductively coupled plasma mass spectrometry (ICP-MS) and cell fractionation methods, revealed the presence of the compound in cytosol, nucleus, and mitochondria. The complex exhibited limited binding to DNA, and using the expression of specific protein markers for cell fate indicated no effect on the expression of stress-sensitive channel components involved in cell volume regulation, weak inhibition of cell proliferation, no increase in apoptosis, and even a reduction in autophagy. The complex is anionic, and the sodium complex had higher solubility compared to the potassium. As the molybdenum complex possibly enters the mitochondria, it is considered as a promising remedy to limit mitochondrial cyanide poisoning following, e.g., smoke inhalation injuries.

TidsskriftACS Pharmacology and Translational Science
Udgave nummer10
Sider (fra-til)907–918
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Funding from the Icelandic Centre of Research grant no. 195726 is gratefully acknowledged. This contribution is based upon collaboration from COST Action CA18202, NECTAR─Network for Equilibria and Chemical Thermodynamics Advanced Research, supported by COST (European Cooperation in Science and Technology). Thiago Oliveira is thanked for the determination of the aqueous solubility of 1 and 2 . Technician Dorthe Nielsen is thanked for skilled technical assistance on the many cell experiments.

Publisher Copyright:
© 2022 American Chemical Society.

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