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

Area of Science:

• Inorganic Chemistry
• Materials Science
• Medicinal Chemistry

Background:

• Polyhedral carboranes are known for biological stability and low toxicity.
• While typically anionic or neutral, positively charged carboranes are a recent discovery.
• Research is exploring novel carborane derivatives for therapeutic applications.

Purpose of the Study:

• To evaluate the in vitro antiproliferative effects of selected carboranes against human cancer cell lines.
• To assess off-target toxicity of these carboranes in normal cell lines.
• To synthesize and characterize novel dicationic polyhedral boranes for potential enhanced efficacy.

Main Methods:

• In vitro antiproliferative assays using a panel of human cancer cell lines.
• Off-target toxicity evaluation on normal cell lines.
• Synthesis and characterization of novel dicationic polyhedral boranes.
• Investigation of reversible cage-opening mechanisms triggered by base or H2/base and reversed by acid.

Main Results:

• Monocationic carborane o-2a demonstrated significant anticancer activity, surpassing doxorubicin and cisplatin with a favorable resistance factor (RF ≈ 1).
• The first dicationic polyhedral boranes were successfully synthesized and found to be water-stable.
• These dications exhibit reversible closo-/nido- cage opening triggered by specific chemical conditions (DMAP or Et3N/H2) and reversible by acid.
• One cage-opening mechanism involves a proton-coupled electron transfer process.

Conclusions:

• Positively charged carboranes, particularly monocationic o-2a, show promising anticancer potential.
• Novel dicationic polyhedral boranes represent a new class of compounds with unique reactivity.
• The reversible cage-opening property offers potential for controlled release or activation mechanisms in future applications.