Labeled Undecahydro-closo-dodecaborates Based on Azo Dyes for Boron Neutron Capture Therapy: Synthesis, Characterization, and Visualization in Cells.

A general approach to the synthesis of novel boronated azo dyes derived from undecahydro-closo-dodecaborates as a convenient preparation of dye labeled for boron neutron capture therapy (BNCT) is described. The method focused on the synthesis of two classes of dye-labeled dodecaborate anions. One is the reaction of (CH3)4NB12H11NH3- with NaNO2 in acetonitrile/water to give its diazonium salt which consequently reacted with substituted phenols to produce boronated azo-dyes (B12H11-N=N-Ar-, Ar = 4-HOC6H5, 1-naphthol, 2-naphthol, 2,3-(HO)2C6H4, 3-MeO-4-HOC6H4, 2-HO-5-MeOC6H4, and 4-Me2N-C6H4). The second is the reaction of aryldiazonium salt as couplers with disodium salt of dodecaborates (B12H11X2-, X = SH or OH) to yield substituted dodecaborate azo-dyes (HXB12H10-N=N-Ar-, Ar = para-bromo, para-nitro, para-carboxy, meta-carboxy, para-sulfonamide, and para-sulfonic acid). The results show the expected effect of the various substituents on the efficiency of the coupling reactions. Extension of similar strategies to tyrosine and 5-(para-aminophenyl)-10,15,20-triphenylporphyrin diazonium salt, we succeeded to get dodecaborate anion containing amino acid or porphyrin as candidates for BNCT, respectively. Dye-labeled dodecaborates were obtained in acceptable yields. The proposed methodology provides not only a convenient way to synthesize libraries of boron cluster modified azo dyes for various applications but also for the visualization of boron clusters in cells.