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

Kazutaka Hirakawa; Syunsuke Takai; Hiroaki Horiuchi; Shigetoshi Okazaki

doi:10.1021/acsomega.0c04303

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

ACS Omega. 2020 Oct 12;5(42):27702-27708. doi: 10.1021/acsomega.0c04303. eCollection 2020 Oct 27.

Authors

Kazutaka Hirakawa^{1

2}, Syunsuke Takai¹, Hiroaki Horiuchi³, Shigetoshi Okazaki⁴

Affiliations

¹ Applied Chemistry and Biochemical Engineering Course, Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University, Johoku 3-5-1, Naka-ku, Hamamatsu 432-8561, Japan.
² Department of Optoelectronics and Nanostructure Science, Graduate School of Science and Technology, Shizuoka University, Johoku 3-5-1, Naka-ku, Hamamatsu 432-8561, Japan.
³ Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Tenjin-cho 1-5-1, Kiryu 376-8515, Japan.
⁴ Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Handayama 1-20-1, Higashi-ku, Hamamatsu 431-3192, Japan.

Abstract

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.