Improved Synthetic Method of Benzo[a]pheno-selenazinium Phototherapeutic Agents

Abstract Benzo[a]phenoselenazinium dyes are excellent photodynamic therapeutic agents that have a red absorption (660 nm), high singlet oxygen quantum yield (>0.8), and good water-solubility and liposolubility. Bis-(3-diethylaminophenyl) diselenide, the most important intermediate for the synthesis of benzo[a]phenoselenazinium dyes, is previously prepared in one pot through 3 steps, during which special care is needed for the preparation of Grinard reagent and toxic selenium vapor. In this work, we employed CuO nanopowder to directly couple haloaniline with selenium to obtain pure bis-(3-diethylaminophenyl) diselenide (one step) under a mild condition with a high reaction yield without the need of column chromatography. Four benzo[a]phenoselenazinium dyes, 5a-d, were easily prepared using the improved synthesis method; and their phototoxicity in living cells were investigated. The improved method could be employed in large-scale synthesis of benzo[a]phenoselenazinium dyes, thereby may stimulate the photodynamic study of this type of photosensitizer.