Pundlik, Raul Kusaji

Turning an Antioxidant into a Prooxidant : Light-induced Mitochondrial Apoptosis in Mammalian Cells by an Ergothioneine-based Neutral Small Molecule / - Bangalore : Indian Institute of Science, 2025 - viii, 201 p. : col. ill. ; e-Thesis 18.98 Mb

Includes references

PhD ; 2025 ; Inorganic and Physical Chemistry (IPC)

Mitochondria-targeted compounds gained significant interest due to their applications in fundamental research, diagnostics, and therapeutics. In this work, we present a detailed investigation of the ergothioneine-based mitochondria-targeted neutral molecule, which is an antioxidant in the dark and turns prooxidant in light inside mammalian cells. This molecule was designed using a fragment-based approach for simultaneous mitochondrial imaging and targeted antioxidant activity. However, it forms a charge-separated state within 10 picoseconds under visible light, leading to triplet-state formation upon charge recombination. Mitochondrial biomolecules first reduce this redox-active triplet state to its one-electron reduced form, which reduces molecular oxygen via one-electron transfer to form superoxide radicals selectively inside mitochondria. This leads to mitochondrial lipid peroxidation, increased mitochondrial membrane permeability transition pore formation, mitochondrial depolarization, and eventually, apoptotic cell death.


Mitochondria targeting
Mitochondria
Antioxidant
Photoredox
Phototoxicity
Triplet state
Chemical Biology

616.01816 / PUN