Photoactivatable aryl amide substituted fatty acid protonophores

Aryl amide substituted fatty acids facilitate transmembrane proton transport and uncouple mitochondrial oxidative phosphorylation in cells, leading to cell death. Photocaging is a potential strategy to enable light-controlled activation of mitochondrial uncouplers with spatio-temporal control. In this work, aryl amide substituted fatty acid protonophores were photocaged with ortho-nitrobenzyl and 4,5-dimethoxy-2-nitrobenzyl groups. The caged protonophores could be activated by irradiation with UV light, demonstrated in vesicular transport assays and in vitro against MDA-MB-231 breast cancer cells.