There are two branches in boron medicinal chemistry: the first focuses on single boron atom compounds, and the second utilizes boron clusters. Boron clusters and their heteroatom counterparts belong to the family of cage compounds. A subset of this extensive class of compounds includes dicarbadodecaboranes, which have the general formula C2B10H12, and their metal biscarboranyl complexes, metallacarboranes, with the formula [M(C2B10H12)2(-2)]. The unique properties of boron clusters have resulted in their utilization in applications such as in pharmacophores, as scaffolds in molecular construction, and as modulators of bioactive compounds. This Perspective presents an overview of the properties of boron clusters that are pertinent for drug discovery, recent applications in the design of various classes of drugs, and the potential use of boron clusters in the construction of new pharmaceuticals.

Boron clusters are polyhedral boron hydrides with unique properties, and they are becoming increasingly widely used in biology and medicine, including for boron neutron capture therapy (BNCT) of cancers and in the design of novel bioactive molecules and potential drugs. Among boron cluster types, icosahedral boranes, carboranes, and metallacarboranes are particularly interesting, and there is a need for basic studies on their interaction with biologically important molecules, such as proteins. Herein, we report studies on the interaction of selected boron clusters and their derivatives with serum albumin, the most abundant protein in mammalian blood. The interaction of boron clusters with albumin was examined by fluorescence quenching, circular dichroism, dynamic and static light scattering measurements and MALDI-TOF mass spectrometry. Our results showed that metallacarboranes have the strongest interaction with albumin among the tested clusters. The observed strength of boron cluster interactions with albumin decreases in order: metallacarboranes [M(C2B9H11)2]− > carboranes (C2B10H12) >> dodecaborate anion [B12H12]2−. Metallacarboranes first specifically interact with the binding cavity of albumin and then, with increasing compound concentrations, interact non-specifically with the protein surface. These findings can be of importance and are useful in the development of new bioactive compounds that contain boron clusters.

Carboranes (dicarba-closo-dodecaboranes) are a class of carbon-containing polyhedral boron-cluster compounds showing remarkable hydrophobic character, chemical and thermal stability, and resistance to catabolism in biological environment. These features allow application of boron clusters as new hydrophobic core structure in biologically active molecules that interact hydrophobically with proteins, thus facilitating new drug design. A review with 45 references.