Synthesis and characterization of nido-carborane-cobalamin conjugates

Abstract Three vitamin B 12 (cyanocobalamin) conjugates bearing one nido -carborane molecule or two nido -carborane molecules linked to the propionamide side chains via a four carbon linker have been synthesized. Reaction of o-carboranoylchloride with 1,4-diaminobutane in pyridine produced nido -carboranoyl(4-amidobutyl)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 11 B nuclear magnetic resonance demonstrated that during the reaction of o-carboranonylchloride with diaminobutane one of the boron atoms was eliminated. In vitro biological activity of the cyanocobalamin- nido -carborane conjugates was assessed by the unsaturated vitamin B 12 binding capacity assay. When compared with 57 Co cyanocobalamin, the biological activity of cyanocobalamin-b- nido -carborane, cyanocobalamin-d- nido -carborane, and cyanocobalamin-b-d-bis- nido -carborane conjugates were 92.93%, 35.75%, and 37.02%, respectively. These findings suggest that the 10 B cobalamin conjugates might be useful agents in treating malignant tumors via neutron capture therapy.