Octachloro-fluorescein: Synthesis and photosensitizer performance evaluation

Abstract Fluorescence image-guided photodynamic therapy (PDT) receives great attention since it provides both the diagnostic and therapeutic information. Theoretically, fluorescence and the photodynamic performance (singlet oxygen) can be traced back to the same origin, namely the Jablonski energy diagram. Therefore, designing photosensitizers with balanced fluorescence and singlet oxygen generation is essentially important. Heavy atom effect (HAE) is an effective approach for designing highly efficient photosensitizers, but at the sacrifice of fluorescence. Herein, through analysis of the well-known fluorophore fluorescein and the photosensitizer Rose Bengal (RB), a new kind of photosensitizer, octachloro-fluorescein (OCF), was designed and synthesized. Structurally, OCF was obtained through anchoring chlorine atoms (heavier than H but lighter than I) onto all the existing open sites of fluorescein, resting in a 5-fold singlet oxygen quantum yield increase over fluorescein, but a much higher fluorescence quantum yield (Φfl = 0.628) over RB. The photodynamic performance of OCF was characterized both photophysically and photochemically. Besides, the image-guided PDT performance of OCF was further evaluated with HeLa cells, demonstrating that elegant heavy atom substitution of fluorescein may provide an effective way of balancing the fluorescence and singlet oxygen generation.