Half- and Mixed-Sandwich Transition Metal Dicarbollides andnido-Carboranes(-1) for Medicinal Applications

Abstract

Today, medicinal chemistry is still clearly dominated by organic chemistry, and most of the marketed drugs are purely organic molecules that can incorporate nitrogen, oxygen, and halogens besides carbon and hydrogen. On the other hand, commercial boron‐ based drugs are still rare [1]. Besides bortezomib, tavaborole (AN2690), crisaborole (AN2728), epetraborole (AN3365), and SCYX‐7158 (AN5568) [2], l‐4‐(dihydroxybo­ ryl)phenylalanine (BPA) and sodium mercapto‐undecahydro‐closo‐dodecaborate (BSH) are used as drugs in boron neutron capture therapy (BNCT) [3–5]. Like carbon, boron readily forms compounds with covalent boron–hydrogen bonds and also boron–boron interactions. However, in contrast to hydrocarbons, boranes prefer the formation of polyhedral clusters with fascinating globular architectures [6]. Most boranes are unstable in aqueous environment; an exception is closo‐B12H12. In contrast, polyhedral carboranes, in which two BH– units of closo‐B12H12 are replaced by two CH vertices (closo‐C2B10H12, dicarba‐closo‐dodecaborane(12), carborane or carbaborane), have remarkable biological stability. Furthermore, the two carbon atoms are versatile starting points for various organic modifications. Carboranes are of special interest due to their unique properties that cannot be found in organic counterparts. These unique properties are based on the element boron, due to its inherent electron deficiency, lower electronegativity, and smaller orbital size compared to carbon. Of the borane clusters and heteroboranes, the three dicarba‐closo‐dodecaborane(12) isomers (ortho (1,2‐), meta (1,7‐), and para (1,12‐dicarba‐closo‐dodecaborane(12)), each of which has specific electronic properties, have attracted much interest. Besides the use Half‐ and Mixed‐Sandwich Transition Metal Dicarbollides and nido‐Carboranes(–1) for Medicinal Applications Benedikt Schwarze, Marta Gozzi, and Evamarie Hey‐Hawkins*