Isomeric Ir(III) complexes for tracking mitochondrial pH fluctuation and inducing mitochondria disfunction during photodynamic therapy

Mitochondrial pH is known to be alkaline (near 8.0) and has emerged as a potential factor for mitochondrial function and disorder. Here we investigate two pairs of isomeric phosphorescent Ir(III) complexes (1-4) with mitochondrial pH-responsive property and mitochondria disfunction during photodynamic therapy. These complexes are designed to function by controlling protonation of the benzimidazole and carboxyl groups. 1 and 2 exhibit enhancement of emission intensity and blue-shift emission change in response to pH alterations from 6.0 to 8.0. They have ideal pKa values (7.49 for 1, 7.41 for 2) and show specific phosphorescence staining of mitochondria in situ, thereby allowing monitoring mitochondrial pH in live cells. 3 and 4 produce abundant intracellular ROS and exhibit highly phototoxicities against cancer cells. Interestingly, these pH-responsive probes can be utilized to monitor the change of mitochondrial pH and mitochondrial damage upon photodynamic therapy (PDT), which provides a convenient method for in-situ monitoring of therapeutic effect and assessment of treatment outcome.