Presentation Information
[P03-341]Synthesis of platinum porphyrin conjugated with a physical quencher of singlet oxygen for low-phototoxic intracellular oxygen concentration imaging
○Kohei Miura1, Shunsuke Odai1, Hidehiro Ito1, Toshiaki Kamachi1 (1. Department of Life Science and Technology, Institute of Science Tokyo (Japan))
Keywords:
Intracellular oxygen imaging,Phosphorescence,Platinum porphyrin,Dendrimer,Singlet oxygen quencher
Oxygen is essential for aerobic organisms, and various methods have been developed to measure tissue and cellular oxygen levels. Optical techniques based on phosphorescence quenching by oxygen are suitable for intracellular oxygen concentration imaging because they allow sequential monitoring and non-invasive measurements. Pt(II) meso-tetrakis(4-carboxyphenyl)porphyrin (PtTCPP) has been used as a phosphorescent dye for intracellular oxygen concentration imaging. However, singlet oxygen generated during phosphorescence quenching of PtTCPP or other phosphorescent dyes can cause cellular damage. Therefore, phosphorescent dyes with reduced phototoxicity are required.
Singlet oxygen can be quenched by various antioxidant compounds. Chemical quenchers are generally unsuitable for deactivating singlet oxygen because they react with it and may produce harmful oxidation products. In contrast, physical quenchers form a charge-transfer complex with singlet oxygen and subsequently release the ground state oxygen without undergoing oxidation or being consumed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) is known to be highly effective among physical quenchers of singlet oxygen. This bicyclic amine possesses two pKa values (3.0 and 8.8), allowing one amine to be unprotonated at neutral pH, which enables efficient physical quenching in biological media.
The addition of large amounts of singlet oxygen quenchers could suppress cellular damage. However, this approach may interfere with intracellular signal transduction, as singlet oxygen also plays a role in cellular signaling pathways. Therefore, it is ideal to position the quencher close to the dye molecule. Based on this concept, we designed a porphyrin–DABCO conjugate using porphyrin-cored dendrimers as scaffolds. These structures consist of poly(L-lysine) dendrons as building blocks and surface units, which enhance the water solubility of the dye molecule.
In this study, we synthesized a platinum porphyrin–DABCO conjugate to suppress cellular damage caused by singlet oxygen. In this conjugate, the singlet oxygen generated by phosphorescence quenching can be deactivated by DABCO. The conjugate showed oxygen-responsive phosphorescence and suppressed singlet oxygen generation. Furthermore, the conjugate accumulated in the cells and successfully stained them.
Singlet oxygen can be quenched by various antioxidant compounds. Chemical quenchers are generally unsuitable for deactivating singlet oxygen because they react with it and may produce harmful oxidation products. In contrast, physical quenchers form a charge-transfer complex with singlet oxygen and subsequently release the ground state oxygen without undergoing oxidation or being consumed. 1,4-Diazabicyclo[2.2.2]octane (DABCO) is known to be highly effective among physical quenchers of singlet oxygen. This bicyclic amine possesses two pKa values (3.0 and 8.8), allowing one amine to be unprotonated at neutral pH, which enables efficient physical quenching in biological media.
The addition of large amounts of singlet oxygen quenchers could suppress cellular damage. However, this approach may interfere with intracellular signal transduction, as singlet oxygen also plays a role in cellular signaling pathways. Therefore, it is ideal to position the quencher close to the dye molecule. Based on this concept, we designed a porphyrin–DABCO conjugate using porphyrin-cored dendrimers as scaffolds. These structures consist of poly(L-lysine) dendrons as building blocks and surface units, which enhance the water solubility of the dye molecule.
In this study, we synthesized a platinum porphyrin–DABCO conjugate to suppress cellular damage caused by singlet oxygen. In this conjugate, the singlet oxygen generated by phosphorescence quenching can be deactivated by DABCO. The conjugate showed oxygen-responsive phosphorescence and suppressed singlet oxygen generation. Furthermore, the conjugate accumulated in the cells and successfully stained them.
Comment
To browse or post comments, you must log in.Log in