Synthesis and tumor-uptake study of phosphate esters of polyhedral hydroxyboranes

The phosphorylations of B12H11OH2-,B12H10(OH)2-2-, and B20H17OH4-with POCl3 and (C6H5O)2POCl were investigated and the following derivatives were isolated: B12H11OPO3H3-,B12H11OPO3H2-2-,B12H11OPO(OC6H5)-2-2 minus, B12H11OPO(OC6H5)OH2 minus, b12h10(op2o6h2)2-4 minus, B12H10(OPO3H2)2-2 minus, B12Br10(OPO3H)2-4 minus, B12H10[O-PO(OC6H5)2]2-2 minus, B20H18OP2O6H2-4 minus, B20H18OPO3H2-3 minus. The B-O-P bonds proved very resistant to hydrolysis and the phosphates were administered in the for of Na+ salts at pH 7.2 to rats bearing subcutaneous glioma. The boron concentrations in tumors and the tumor/blood concentration ratios were compared with those of parent hydroxy derivatives. Except when the POH function was blocked by phenyl groups the phosphorylation invariably resulted in a greatly enhanced uptake of the borane into tumors and improved the tumor/blood boron ratio. The phopshate function appears to be one of the most effective handles for the incorporation of boron into brain tumors and the compounds show considerable promise for use in the neutron capture therapy of brain tumors.