Unraveling the Correlation between Biological Effects and Halogen Substituents in Cobalt bis(dicarbollide)

Over the past decade, considerable scientific attention has been given to adapting cobalt bis(dicarbollides) as innovative agents with various biomedical applications. Although the studied compounds show great potential in this field, only a few reports have explored broad, well-thought-out libraries of derivatives to correlate their structure with biological activity. In this study, we investigate a panel of [CoSAN]^- derivatives substituted with fluorine, chlorine, bromine, and iodine in order to elucidate the impact of the halogen presence on antimicrobial action and selectivity over mammalian cells. We present the first evidence that increasing the atomic mass of a substituent improves the biological activity of a derivative. Our results demonstrate that the addition of a single iodine atom to the [CoSAN]^- core results in the most selective antibacterial outcome,especially toward Staphylococcus aureus ATCC 6538. The described correlation between the lipophilicity parameter and the activity of the compounds toward both bacteria and human cell lines highlights the importance of a conscious design method to obtain the most desirable [CoSAN]--based derivatives.