Molybdenum(II) allyl dicarbonyl complexes with 3-(2-pyridyl)pyrazole as potential CO-releasing molecules, antibacterial and antitumoral agents

Molybdenum-based CO-releasing molecules (CORMs) are attracting interest for biological and therapeutic applications. In this work two new complexes, [Mo(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)X(CO)<sub>2</sub>(Hpypz)] [X = Cl (1), Br (2); Hpypz = 3-(2-pyridyl)pyrazole] have been synthesized, characterized, and evaluated for their CO-release capacity, as well as antimicrobial and anticancer potential. The evaluation of the CO-release properties by the deoxymyoglobin‑carbonmonoxymyoglobin assay showed that the two complexes are comparably slow CO releasers in aqueous systems, showing a half-life of several hours, and sustained CO release over the course of the assay (6 h). Studies of biological activity were performed with complex 1 due to its better aqueous solubility. The antibacterial activity was investigated by determination of the minimum inhibitory and minimum bactericidal concentrations with the microdilution assay for gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative Escherichia coli strains. Complex 1 displayed appreciable concentration-dependent bactericidal activity against both strains. The cytotoxicity of complex 1 was evaluated on human melanoma cells (A375) and immortalized nontumorigenic keratinocytes (HaCaT). Complex 1 exhibited selective cytotoxicity, significantly reducing the cell viability of A375 cells in a dose-dependent manner while having a lower effect on HaCaT cells, suggesting its antitumor potential against melanoma. In contrast, the precursor complex [Mo(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)Cl(CO)<sub>2</sub>(CH<sub>3</sub>CN)<sub>2</sub>] showed reduced activity against A375 cells and higher toxicity toward HaCaT cells, highlighting the beneficial impact of the bidentate 3-(2-pyridyl)pyrazole ligand.

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Journal
Journal of Inorganic Biochemistry
Published
2026-01-28
DOI
https://doi.org/10.1016/j.jinorgbio.2026.113244
Primary Topic
Heme Oxygenase-1 and Carbon Monoxide
Type
article
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article

Molybdenum(II) allyl dicarbonyl complexes with 3-(2-pyridyl)pyrazole as potential CO-releasing molecules, antibacterial and antitumoral agents

Martyn Pillinger, Ana C. Gomes, Isabel B. Calhau, Isabel S. Gonçalves et al.
Journal of Inorganic Biochemistry
Heme Oxygenase-1 and Carbon Monoxide
article

Molybdenum(II) allyl dicarbonyl complexes with 3-(2-pyridyl)pyrazole as potential CO-releasing molecules, antibacterial and antitumoral agents

Martyn Pillinger, Ana C. Gomes, Isabel B. Calhau, Isabel S. Gonçalves, Carla Pereira, Sofia M. Bruno, Laura Oliveira, Helena Oliveira, Adelaide Almeida, Fernanda Rosário
article en

Abstract

Molybdenum-based CO-releasing molecules (CORMs) are attracting interest for biological and therapeutic applications. In this work two new complexes, [Mo(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)X(CO)<sub>2</sub>(Hpypz)] [X = Cl (1), Br (2); Hpypz = 3-(2-pyridyl)pyrazole] have been synthesized, characterized, and evaluated for their CO-release capacity, as well as antimicrobial and anticancer potential. The evaluation of the CO-release properties by the deoxymyoglobin‑carbonmonoxymyoglobin assay showed that the two complexes are comparably slow CO releasers in aqueous systems, showing a half-life of several hours, and sustained CO release over the course of the assay (6 h). Studies of biological activity were performed with complex 1 due to its better aqueous solubility. The antibacterial activity was investigated by determination of the minimum inhibitory and minimum bactericidal concentrations with the microdilution assay for gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and gram-negative Escherichia coli strains. Complex 1 displayed appreciable concentration-dependent bactericidal activity against both strains. The cytotoxicity of complex 1 was evaluated on human melanoma cells (A375) and immortalized nontumorigenic keratinocytes (HaCaT). Complex 1 exhibited selective cytotoxicity, significantly reducing the cell viability of A375 cells in a dose-dependent manner while having a lower effect on HaCaT cells, suggesting its antitumor potential against melanoma. In contrast, the precursor complex [Mo(η<sup>3</sup>-C<sub>3</sub>H<sub>5</sub>)Cl(CO)<sub>2</sub>(CH<sub>3</sub>CN)<sub>2</sub>] showed reduced activity against A375 cells and higher toxicity toward HaCaT cells, highlighting the beneficial impact of the bidentate 3-(2-pyridyl)pyrazole ligand.

Journal of Inorganic BiochemistryVol. 278
University of Aveiro (PT)
Clean water and sanitation
Openalex Percentile: Top 75%
Heme Oxygenase-1 and Carbon Monoxide
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