Asymmetric ZnPc-TEG photosensitizers: the effect of Pc substitution on phototoxicity

作者：Muli Dominic K; Rajaputra Pallavi; You Youngjae^*; McGrath Dominic V

来源：Tetrahedron Letters, 2015, 56(45): 6236-6239.

DOI：10.1016/j.tetlet.2015.09.101

• Peripheral and non-peripheral substitution
• Asymmetric ZnPc
• Water solubility
• Photodynamic therapy
• Phthalocyanine

Asymmetric zinc phthalocyanine (ZnPc) isomers with triethylene glycol (TEG) moieties in the peripheral (1a) and non-peripheral (1b) substitution were designed, synthesized, characterized, and their phototoxicity on colon-26 cells evaluated. TEG moieties as water solubilizing groups were incorporated at peripheral or non-peripheral positions to investigate the effect of their position on the Pc on the photodynamic activity. UV/vis analyses indicated a small red-shifting of the Q band of the non-peripheral ZnPc-TEG 1b (ca. 4 nm) relative to la in dichloromethane and THF. n-Octanol/pH 7.4 buffer partition coefficients revealed that 1b was marginally more hydrophilic than 1a with log D-7.4 values of 2.44 and 2.46, respectively. Fluorescence emission aggregation studies indicate that 1b is ca. 61% (DMSO) and 32% (phosphate buffer) less aggregated than the peripherally substituted ZnPc la suggesting that non-peripheral substitution decreased overall aggregation of the photosensitizers. Singlet oxygen generation studies are reported. Both ZnPc-TEGs showed negligible dark toxicity on colon 26 cells with 10 mu M la and 1b. Irradiation (690 nm, 45 J/cm(2)) of the cells produced an IC50 value >25 mu M for la and an IC50 value between 1 and 5 mu M for lb. Overall, the non-peripheral isomer lb was found to be more photodynamically active.

• 出版日期2015-11-4