Synthesis and characterization of nido-carborane-cobalamin conjugates

Three vitamin B-12 (cyanocobalamin) conjugates bearing one nido-carborane m olecule or two nido-carborane molecules linked to the propionamide side cha ins via a four carbon linker have been synthesized. Reaction of o-carborano ylchloride with 1,4-diaminobutane in pyridine produced nido-carboranoyl(4-a midobutyl)amine, which was linked to the b- and d-monocarboxylic acids and the b,d-dicarboxylic acid of cyanocobalamin. Mass spectrometry analysis as well as B-11 nuclear magnetic resonance demonstrated that during the reacti on of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin-nido-carbora ne conjugates was assessed by the unsaturated vitamin B-12 binding capacity assay. When compared with Co-57 cyanocobalamin, the biological activity of cyanocobalamin-b-nido-carborane, cyanocobalamin-d-nido-carboranct, and cya nocobalamin-b-d-bis-nido-carborane conjugates were 92.93%, 35.75%, and 37.0 2%, respectively. These findings suggest that the B-10 cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture th erapy. NUCL MED BIOL 27;1:89-92, 2000. (C) 2000 Elsevier Science Inc. All r ights reserved.