Polyhedral boranes BNCT

Since the a particles travel only 10 tim or less distance, the B nucleii-localized cancer cells are destroyed selectively. However, the estimated amount of B nucleii needed for tumor destruction is approximately 10 atoms or 10 30 tg B/g tumor. Therefore, the polyhedral borane and carborane-confaining biomolecules are found to be ideal for use in BNCT... 

The search for potential BNCT drugs has re-awakened interest in the organic chemistry of the 12-vertex polyhedral boranes.1 The most widely studied chemistry is of o-carborane, where two carbon atoms are available for a number of organic reactions.2 Most substituted carboranes are prepared either by interaction of alkynes with decaborane,3 cross-coupling of Li, Na, Mg-carboranes with electrophiles 4 or by the organic reactions on the side chains (Scheme 1). ... 

Carboranes - polyhedral boranes containing carbon in the framework - have been known for over 35 years, and their intrinsic stability, versatility, structural variety, and electronic properties have been put to use in a number of diverse areas, [1] for example in the synthesis of extraordinarily heat-stable polymers, in BNCT (boron neutron capture therapy), as ligands in metallacarborane catalysts, as com-plexing agents for extraction of metal ions, as precursors to ceramics, conducting polymers, and nonlinear optical materials, as anticancer... 

The polyhedral borane ion [n-B2oH,8] reacts with liquid ammonia in the presence of a suitable base to produce an apical-equatorial isomer of the [B2oH,7NH3] ion. This species undergoes acid-catalyzed rearrangement to an apical-apical isomer. The sodium salts of both isomers were encapsulated in unilamellar liposomes, composed of distearoyl phosphatidylcholine/cholesterol, and investigated as boron delivery agents for BNCT (Feakes et al. 1994 Shelly et al. 1992). 

Adams, L., S. N. Hosmane, J. E. Eklund, J. Wang, and N. S. Hosmane. 2002. Novel route to boron-10 enriched pentaborane(9) from boric acid and conversion to nido- °BioHi4 and anti- BigH22 Synthetic advance in polyhedral borane chemistry and in BNCT research. In Proceedings of the First International Boron Symposium, ed. K. Erarslan, pp. 129-133. Kiitahya, Turkey Dumlupinar University Press. 

Recently, some other boron carriers were used to deliver polyhedral boranes into tumor cells. One of the most interesting and new direction is developments in the BNCT driven by nanotechnology [142-147]. This subject will not be discussed here since a special chapter is planned in this book. Carboranylquinazolines [148], carboranyl aminoalcohols [149], carboranyl-a-acyloxy-amides [150], carboranyl glycophosphonates [151], conjugates of icosahedral dicarboranes with cobalt bis(dicarbollide) [152], and platinum complexes containing carborane [153] have been obtained as potential candidates for BNCT. 

Sulfhydryl derivatives of polyhedral borane anions have been of interest to BNCT researchers for many years because of the mercaptoundecahydro-c/o5t -dodecaborate dianion ([B,2H SH] , abbreviated borocaptate sodium (BSH) that has been used in a variety of preclinical and clinical BNCT trials (Hawthorne, 1993 Soloway et al., 1998 Hawthorne and Lee, 2003). Although only the free sodium salt of the [B,2H SHp has been used in the trials researchers have investigated the biodistribution of BSH encapsulated in liposomes (Shelly et al., 1992 Maruyama et al., 2004 Doi et al.. 

Radionuclide targeting using polyhedral borane anions as pendant groups can in many cases utilize compounds which have been developed for use as boron carriers in BNCT. Functional groups which enable boron hydride coupling with tumor-seeking molecules are amino acids (-CH(NH2)COOH), amines (-NH2), acids (-COOH), isocyanates (-NCO), and isothiocyanates (-NCS). A number of derivatives containing these functionalities were prepared and described above. 

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