Ph-controlled Photodynamic Therapy

Reversible on-off switching of singlet oxygen generation, the key therapeutic property of photodynamic therapy cancer treatment, has been demonstrated by Donal O'Shea and coworkers of University College Dublin, in Ireland (J. Am. Chem. Soc. 2005, 127, 16360). Photodynamic therapy utilizes a chemical reagent that targets a tumor and is activated to generate cell-killing singlet oxygen molecules by irradiating a site with red light. O'Shea's group realized that attaching an amine-containing group to photosensitive BF₂-chelated azadipyrromethenes (shown) would allow a new level of selectivity for singlet oxygen generation by taking advantage of the slightly acidic pH inherent to tumor tissues: The protonated amine allows formation of singlet oxygen, whereas the deprotonated version doesn't. When R is –C₆H₄CH₂N(CH₂CH₃)₂ and R' is –C₆H₅, for example, singlet oxygen generation when the amine is protonated is 8.5 times greater than at neutral pH. The amine-containing reagents efficiently induce cell death in fibroblast cells, the researchers note. Optimizing the reagents could lead to their clinical use, they add.