Photolabile Protecting Groups for Nucleosides : Mechanistic Studies of the 2-(2-Nitrophenyl)ethyl Group

Abstract

The photochemistry of several 2-(2-nitrophenyl)ethyl-caged compounds including caged thymidine nucleosides was studied by nanosecond laser flash photolysis and stationary illumination experiments with quantitative HPLC analysis for quantum yields and product distribution. Effects of solvent basicity and acidity were investigated by varying the H2O content and HCl concentration, respectively, in MeCN/H2O mixtures. For all compounds 1 - 7 investigated, intramolecular H abstraction by the nitro group from the exocyclic α-position with respect to the aryl moiety was found to be the primary process. The protolytic dissociation equilibrium of the resulting aci-nitro compound was kinetically characterized in the 0.1 - 10 s time region. In general, two reaction channels compete for the aci-nitro compound and its anion: β-elimination of the caged compound occurs from the anion, while from the undissociated aci-nitro compound, a nitrosobenzene derivative is formed with no release of the caged compound. The yield ratio of these two reaction channels can be controlled through shifts in the protolytic dissociation equilibrium of the aci-nitro compound. In solutions with either low basicity (H2O-free MeCN) or high acidity (higher concentration of HCl in H2O/MeCN), two as yet unidentified products are formed, each one specifically for one of the mentioned conditions.