The Far Side of Carboranes: Anticancer Active Monocations and Ambiently Stable Dications

ABSTRACT Polyhedral carboranes are highly biologically stable, non‐toxic clusters. Whereas they are typically encountered in anionic or neutral forms, positively charged species have only recently been discovered. The in vitro antiproliferative effects of selected carboranes were assessed using a panel of human cancer cell lines, and off‐target toxicity was evaluated at normal cell lines. The results demonstrated significant anticancer activity and a favorable resistance factor (RF ≈ 1) for monocationic carborane o ‐2a , surpassing the effects of doxorubicin and cisplatin . In pursuit of even more efficient substrates, the first dicationic polyhedral boranes were synthesized. These water‐stable dications exhibit a reversible closo‐ / nido‐ cage opening, triggered either by a strong base (DMAP) or by a combination of triethylamine and molecular hydrogen, and reversed upon the addition of acid. The former transformation proceeds without a redox change, while the latter involves a H 2 /2H + conversion in a proton‐coupled electron process.