Carborane Chemistry and Applications in Drug Design

Carboranes are three-dimensional carbon–boron clusters characterised by exceptional thermal and chemical stability and a unique cage-like architecture. Their delocalised bonding imparts aromaticity comparable to benzene, yet with a globular geometry that confers high lipophilicity and resistance to metabolic degradation. Three isomers of closo-carborane (ortho, meta and para) offer distinct electronic and steric profiles, enabling fine-tuning of drug-like properties. Functionalisation of individual boron vertices via catalytic cage B–H activation has become a powerful tool for introducing diverse substituents, thereby modulating target affinity, solubility and membrane permeability. In medicinal chemistry, carboranes serve as non-classical pharmacophores in small-molecule enzyme inhibitors, antitumour ligands and boron neutron capture therapy (BNCT) sensitizers. Their capacity to engage in hydrophobic and dihydrogen bonding interactions broadens the design space for selective binding to biomolecular targets. Emerging applications include multifunctional dual sensitizers for photodynamic and boron-based therapies, as well as inorganic membrane carriers that facilitate intracellular delivery of hydrophilic drugs and probes.

Research from Nature Portfolio

Recent studies have demonstrated that dodecaborate clusters can function as anionic inorganic carriers for a broad spectrum of hydrophilic bioactive molecules. The superchaotropic nature of [B12Br12]2– enables transport of peptides, neurotransmitters and antineoplastic agents across liposomal and cellular membranes without nonspecific lysis, offering a platform for delivery of otherwise impermeable therapeutics. Advances in site-selective functionalisation have been achieved through iridium-catalysed borylation of o-carborane cages, allowing precise installation of boronic ester handles on defined B–H sites. These synthetically versatile intermediates serve as entry points for further derivatisation into drug-like scaffolds. Fundamental investigations into the interaction of carboranes and metallacarboranes with serum albumin have revealed isomer-dependent binding affinities and modes, informing pharmacokinetic optimisation by highlighting how cage hydrophobicity and charge distribution influence plasma protein binding and biodistribution.

Carborane Chemistry and Applications in Drug Design publication trend

The graph below shows the total number of articles in carborane chemistry and applications in drug design across all publications each year (not limited to Nature Index journals).

Technical terms

Carborane: A polyhedral carbon–boron cluster exhibiting aromatic character and exceptional stability, used as a three-dimensional pharmacophore.

Pharmacophore: The ensemble of steric and electronic features necessary to ensure optimal interactions with a specific biological target and elicit a desired response.

Boron neutron capture therapy (BNCT): A cancer treatment modality in which boron-containing agents accumulate in tumour cells and, upon neutron irradiation, produce cytotoxic particles.

Superchaotropic cluster anion: A highly polarisable, weakly hydrated anion capable of facilitating membrane translocation of hydrophilic molecules without detergency.

Cage B–H activation: A catalytic method for selective functionalisation of boron–hydrogen vertices within the carborane cage, enabling the introduction of diverse substituents.

References

1. Boron clusters as broadband membrane carriers. Nature (2022).
2. Iridium-catalysed regioselective borylation of carboranes via direct B–H activation. Nature Communications (2017).
3. Interactions of Boron Clusters and their Derivatives with Serum Albumin. Scientific Reports (2017).
4. Carboranes as unique pharmacophores in antitumor medicinal chemistry. Molecular Therapy Oncology (2022).
5. The Boron Advantage: The Evolution and Diversification of Boron’s Applications in Medicinal Chemistry. Pharmaceuticals (2022).