Carboranes BNCT applications

Thomas and Hawthorne have synthesized unimolecular, nanospherical boron-rich dodeca(carboranyl)-substituted closomers (122) (Fig. 71) for their potential application as drug-delivery platforms for BNCT.148 The substituted closomers were synthesized by reacting carborane acid chloride with the dodecahydroxy dodecaborate closomer in methylene chloride by utilizing a threefold excess of the former in triethylamine. The twelve pendant closo-1,2-carborane units in the closomer could... 

The research field of ortho-carborane chemistry continues to expand rapidly mainly due to the commercial availability of ort/fo-carborane itself and the recent interest of these derivatives as agents for BNCT and other applications. Synthesis of these carboranes is still dominated by reactions of decaborane with various alkynes as shown in Table 19 (Figure 2). 3-Substituted derivatives are made by capping the /[Pg.71]

For compounds to be useful in BNCT, they must allow administration to a patient (usually through the blood stream), accumulate or be retained in the tumor, be of low toxicity, and on the basis of the required accumulation, carry as many boron atoms as possible. To achieve the latter, boron clusters are of great value. In this chapter, the chemistry of some clusters is described that have found application in BNCT (see Scheme 2.2-1). The focus is on the o-carborane system dicarba-doso-dodecaborane, C2B1oH12, and its degradation product nido-carborate,... 

The rapid development of carborane chemistry is mainly due to their practical applications. For instance, the potential utility of carborane polymers as gaskets, O-rings, and electrical connector inserts has been reported. Their functionality for solvent extraction of radionuchdes as well as the potential medicinal value of the isoelectronic and isostructural boron analogues of biologically important molecules has been the subject of many review articles. For example, a number of boron compounds have been found to possess anti-inflammatory and antiarthritic activity in animal model studies. Boron compounds have also been implicated in studies designed to probe the importance of the so-called anionic subsite of acetylcholine esterase and Ach receptors. But, by far the most interesting practical apphcations of carboranes are in areas of boron neutron capture therapy (BNCT) and supramolecular assembly. 

In 1999, Komagata et al. described the synthesis of bisphosphonic acids and esters linked through an alkyl spacer to ort/to-carborane (39-41) in a patent application. These boron-containing phosphonates were proposed for use as BNCT agents in the treatment of bone tumors. However, no data concerning the biological activity of these compounds were given. 

Boranes, boron clusters, and in particular, carboranes are of special interest due to their unique properties that cannot be found in organic counterparts. These uniqne properties are based either on the element boron, due to its electron deficiency, or on the structnral featnre of the cluster compound. Borane clusters as a class of materials have a wide range of potential applications. This is not only due to their unique electronic and nuclear features the fields of application, to name but a few, range from materials science through medical applications to catalysis, which will be described in more detail below [13]. Carboranes can be applied as liquid crystals in electro-optical displays [14], non-linear optics [15], and ion-selective electrodes [16] in the materials science arena. If carboranes are vaporized and fired at high temperatures they create boron films that are applied in Tokamak reactors for nuclear fusion [17]. Boranes have furthermore found application in airbag propellant systems in cars [18], as the stationary phase in gas chromatography [19] and in metal ion extraction systems, for example, for nuclear waste [20]. In medical applications, boron neutron capture therapy (BNCT), a special field of anti-cancer therapy, is noteworthy. 

Figure 11.10. Two Zn(ll)-porphyrin molecules bearing four carborane units for applications in BNCT.

---