Carboranes hydrophilic

Oligonucleotides bearing nido-carborane have been synthesized as phospho-diesters using an automated DNA synthesizer (see Scheme 2.2-14) [39]. These oligophosphates are homogeneous, very hydrophilic and are readily taken up into cells. Fluorescein-labeled nido-carboranyl oligomeric phosphate diesters accumulate in the cell nucleus [40]. 

Figure 3 displays the synthesis of a hydrophilic carboracycle whose water-solubility is based upon the presence of eight sulfonate substituents and accompanying sodium cations. The properties of this system and other similar hydrophilic species are the subjects of ongoing research. Variables of interest are the size of the hydrophobic cavity, linker structure and the identity of the hydrophilic groups attached to the carborane cages. 

Lee et al. (2007) succeeded in the synthesis of the double-tailed boron cluster lipids, which have a B12H11S moiety as a hydrophilic function, by S-alkylation of B,2H SH with bromoacetyl and chloroacetocarbamate derivatives of diacylglycerols for a liposomal boron delivery system on BNCT. Altieri et al. (2009) reported on the use of some different examples of liposomes as carriers for BNCT active compounds. Two carborane derivatives, i.e., o-closocarboranyl P-lactoside and l-methyl-o-closocarboranyl-2-hexylthioporphyrazine, were loaded into liposomes. 

Consequently, the hydrophobicity of dicarbadodecaborane (C2B]oH,2) (1-3) isomers increases in the following order l,2-dicarba-cZo5 o-dodecaborane (ort/ o-carborane) (1) electrophilic boron atom in hydrophobic, neutral c/oio-carborane results in the formation of more hydrophilic, anionic n/tZo-carboranes (CjBpHfj). 

S. Fujii, K. Ohta, T. Goto, H. Kagechika, Y. Endo, Acidic heterocycles as novel hydrophilic pharmacophore of androgen receptor ligands with a carborane core structme, Bioorg. Med. Chem., 2009, 17, 344-350. 

In order to solve the problem of the significant toxicity of liposomes prepared from ntdo-carborane lipids 2 and 3, ctoo-dodecaborate has been focused on as an alternative hydrophilic function of boron lipids. BSH is known as a water-soluble divalent c/050-type anion cluster and significantly lowered toxicity (Haritz et al., 1994), and thus has been utilized for clinical treatment of BNCT. Nakamura and coworkers succeeded in the synthesis of double-tailed cZoso-dodecaborate lipids 4a-c and 5a-c, which have a B,2H S-moiety as a hydrophilic function with chirality similar to natural phospholipids, such as distearoylphosphatidylcholine (DSPC), in their lipophilic tails (Lee et al., 2007 Nakamura et al., 2007a). 

Due to the hydrophobicity of carborane, most carborane-contaming amino acids are not soluble in water. In order to increase solubility, some hydrophilic substituents were introduced or the carborane was transformed to the nido-iorm. Several amino acids based on anionic boron hydrides [78,106] and metallacarboranes [67] have been prepared (Figure 7). 

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