Dicobalt(II) helices kill colon cancer cells via enantiomer-specific mechanisms; DNA damage or microtubule disruption. Song, H., Kostrhunova, H., Cervinka, J., Macpherson, J., Malina, J., Rajan, T., Phillips, R., Postings, M., Shepherd, S., Zhang, X., Brabec, V., Rogers, N. J., & Scott, P. CHEMICAL SCIENCE, 15(28):11029–11037, July, 2024.
doi  abstract   bibtex   
Highly diastereoselective self-assembly reactions give both enantiomers (Lambda and Delta) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution; the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Lambda enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Lambda enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s); while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Lambda enantiomer, Delta-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.
@article{song_dicobaltii_2024,
	title = {Dicobalt({II}) helices kill colon cancer cells via enantiomer-specific mechanisms; {DNA} damage or microtubule disruption},
	volume = {15},
	issn = {2041-6520},
	doi = {10.1039/d4sc02541e},
	abstract = {Highly diastereoselective self-assembly reactions give both enantiomers (Lambda and Delta) of anti-parallel triple-stranded bimetallic Co(ii) and Co(iii) cationic helices, without the need for resolution; the first such reaction for Co. The complexes are water soluble and stable, even in the case of Co(ii). Studies in a range of cancer and healthy cell lines indicate high activity and selectivity, and substantial differences between enantiomers. The oxidation state has little effect, and correspondingly, Co(iii) compounds are reduced to Co(ii) e.g. by glutathione. In HCT116 colon cancer cells the Lambda enantiomer induces dose-dependent G2-M arrest in the cell cycle and disrupts microtubule architectures. This Co(ii) Lambda enantiomer is ca. five times more potent than the isostructural Fe(ii) compound. Since the measured cellular uptakes are similar this implies a higher affinity of the Co system for the intracellular target(s); while the two systems are isostructural they have substantially different charge distributions as shown by calculated hydrophobicity maps. In contrast to the Lambda enantiomer, Delta-Co(ii) induces G1 arrest in HCT116 cells, efficiently inhibits the topoisomerase I-catalyzed relaxation of supercoiled plasmid DNA, and, unlike the isostructural Fe(ii) system, causes DNA damage. It thus seems very likely that redox chemistry plays a role in the latter.},
	number = {28},
	urldate = {2024-06-27},
	journal = {CHEMICAL SCIENCE},
	author = {Song, Hualong and Kostrhunova, Hana and Cervinka, Jakub and Macpherson, Julie and Malina, Jaroslav and Rajan, Teena and Phillips, Roger and Postings, Miles and Shepherd, Samantha and Zhang, Xuejian and Brabec, Viktor and Rogers, Nicola J. and Scott, Peter},
	month = jul,
	year = {2024},
	pages = {11029--11037},
}
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