Photooxidation Activity Control of Dimethylaminophenyl-tris-(N-methyl-4-pridinio)porphyrin by pH

To control the activity of photodynamic agents by pH, an electron donor-connecting cationic porphyrin, meso-(N',N'-dimethyl-4-aminophenyl)-tris(N-methyl-p-pyridinio)porphyrin (DMATMPyP), was designed and synthesized. The photoexcited state (singlet excited state) of DMATMPyP was deactivated through intramolecular electron transfer under a neutral condition. The pK _a of the protonated DMATMPyP was 4.5, and the fluorescence intensity and singlet oxygen-generating activity increased under an acidic condition. Furthermore, the protonation of DMATMPyP enhanced the biomolecule photooxidative activity through electron extraction. Photodamage of human serum albumin (HSA) was observed under a neutral condition because a hydrophobic HSA environment can reverse the deactivation of photoexcited DMATMPyP. However, an HSA-damaging mechanism of DMATMPyP under a neutral condition was explained by singlet oxygen production. Therefore, it is indicated that the protein photodamaging activity of DMATMPyP goes into an OFF state under a neutral hypoxic condition. Under an acidic condition, the HSA photodamaging quantum yield by DMATMPyP through electron extraction could be preserved in the presence of a singlet oxygen quencher. Photooxidation of nicotinamide adenine dinucleotide by DMATMPyP was also enhanced under an acidic condition. This study demonstrated the concept of using pH to control photosensitizer activity via inhibition of the intramolecular electron transfer deactivation and enhancement of the oxidative activity through the electron extraction mechanism. Specifically, biomolecule oxidation through electron extraction may play an important role in photodynamic therapy to treat tumors under a hypoxic condition.