Numerous photo-responsive molecules known as photosensitizers activate molecular oxygen to generate highly reactive singlet oxygen, 1 O2 (Scheme 5A). 1 O2, which has a lifespan of only microseconds in water and limited diffusion, leads to oxidation reactions in close proximity to the photosensitizer. Histidine residues are primary targets for 1 O2induced oxidation, undergoing Diels-Alder additions that form reactive endoperoxide intermediates on the imidazole rings.