Study of the Mode and Efficiency of DNA Binding in the Damage Induced by Photoactivated Water Soluble Porphyrins

We have investigated the DNA binding interactions and in vitro photoactivated DNA damage induced by a neutral water soluble porphyrin derivative 5,10,15,20‐tetrakis(2,4,6‐trihydroxyphenyl)porphyrin (TTHPP) and its zinc derivative 5,10,15,20‐tetrakis(2,4,6‐trihydroxyphenyl)porphyrinato zinc(II) (Zn‐TTHPP) upon visible light irradiation through various spectroscopic techniques and employing repair endonucleases. These porphyrin derivatives exhibited high affinity toward DNA through groove binding interactions as evidenced through the UV–vis absorption, emission, circular dichroism spectral and viscosity changes. Interestingly, the free base porphyrin derivative, TTHPP generated efficient singlet oxygen mediated DNA damage sensitive to formamidopyrimidine‐DNA glycosylase (Fpg protein), when compared with its metal derivative and to the well‐known photosensitizer, hematoporphyrin. These results provide direct evidence for the role of DNA binding mode as well as extent of interactions with DNA in the efficiency of photoactivated DNA damage induced by the neutral porphyrins, which are believed to be the ideal candidates for photodynamic therapeutic applications. We describe interactions of neutral and water soluble porphyrins with DNA and their efficiency of photoinduced DNA damage. Uniquely these systems exhibited high affinity for DNA and efficient singlet oxygen mediated DNA damage sensitive to formamidopyrimidine‐DNA glycosylase (Fpg protein), when compared with the well‐known photosensitizer, hematoporphyrin. These results demonstrate the direct evidence for the role of the DNA binding mode and extent of interactions with DNA in the efficiency of the photoactivated DNA damage caused by the neutral porphyrins, which are believed to be the ideal candidates for photodynamic therapeutic applications.