Intramolecular Sensitization of Photocleavage of the Photolabile 2-(2-Nitrophenyl)propoxycarbonyl (NPPOC) Protecting Group: Photoproducts and Photokinetics of the Release of Nucleosides

Novel photolabile protecting groups based on the 2‐(2‐nitrophenyl)propoxycarbonyl (NPPOC) group with a covalently linked thioxanthone as an intramolecular triplet sensitizer exhibit significantly enhanced light sensitivity under continuous illumination. Herein we present a detailed study of the photokinetics and photoproducts of nucleosides caged with these new protecting groups. Relative to the parent NPPOC group, the light sensitivity of the new photolabile protecting groups is enhanced by up to a factor of 21 at 366 nm and is still quite high at 405 nm, the wavelength at which the sensitivity of the parent compound is practically zero. A new pathway for deprotection of the NPPOC group proceeding through a nitroso benzylalcohol intermediate has been discovered to complement the main mechanism, which involves β elimination. Under standard conditions of lithographic DNA‐chip synthesis, some of the new compounds, while maintaining the same chip quality, react ten times faster than the unmodified NPPOC‐protected nucleosides. Higher efficiency at longer wavelength: Photostationary kinetic experiments in solution and tests on oligonucleotide chips demonstrate large increases in the light efficiency of the photolabile 2‐(2‐nitrophenyl)propoxycarbonyl (NPPOC) protecting group due to intramolecular sensitization at wavelengths longer than 350 nm (see figure).