Nanoscopic evaluation on mitochondrial ultrastructures by regulating reactive oxygen species productivity within terpyridyl Zn(ii) complexes with different alkyl chain lengths

Mitochondria targeting complexes are widely utilized as photosensitizers in photodynamic therapy. However, the mechanisms by which they regulate reactive oxygen species (ROS) production at the molecular level and their influence on intracellular mitochondrial signaling and ultrastructures remain rarely studied. Herein, we present two terpyridyl Zn(ii) complexes with different side alkyl chain lengths (Zn-2C and Zn-6C) that lead to low and high ROS productivities in vitro, respectively. Both complexes could enter live cells effectively with minimal dark toxicity and accumulate preferably in the mitochondria. We also demonstrated that Zn-6C, with more efficient ROS productivity, could significantly downregulate the caspase signaling pathway but showed no evident influence on mitochondrial membrane proteins. We also highlighted and compared the mitochondrial ultrastructural variations during such a process by stimulated emission depletion (STED) super-resolution nanoscopy.

Automated summary

This study investigated the mechanisms of two terpyridyl Zn(ii) complexes with different alkyl chain lengths in regulating ROS production, mitochondrial signaling, and ultrastructural variations. The results showed that both complexes could enter live cells and accumulate in mitochondria, and the complex with higher ROS productivity could downregulate the caspase signaling pathway.