Design and Synthesis of BODIPY-Hetero[5]Helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer.

Design of heavy-atom-free triplet photosensitizers (PSs) is a challenge for efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) having efficient ISC which is proportional to their twisting angle. But difficult syntheses and weak absorption profile restrict their use as heavy-atom-free triplet PSs for PDT applications. Boron containing PAHs, BODIPYs are highly recognized for outstanding optical properties. But planar BODIPY dyes have low ISC and thus they are also not very effective as PDT agents. Herein, we designed BODIPY and hetero[5]helicene fused dyes, BODIPY-hetero[5]helicene with red shifted absorbances. All dyes have helical structures and their twisting angles are increased by substitutions at boron-center. The new dyes showed superior optical properties and high ISC with respect to [5]helicene. Interestingly their ISC efficiencies increase proportionally with their twisting angles. Theoretical calculations showed that energy gap of the S1 and T1 states decreases in BODIPY-hetero[5]helicene as compared to planar BODIPY. This enhances their ISC rate which is responsible for high singlet oxygen generation. Finally, their potential applications as PDT agents were investigated and one of the dyes showed efficient cancer cell killing on photo-exposure. This new design strategy will be very useful for future development of heavy-atom-free PDT agents.