Oxidation of ophthalmic drugs photopromoted by inorganic radicals

The rate constants of the reactions of the sulfate (SO4−) and hydrogen phosphate (HPO4−) radicals with the imidazoline derivatives naphazoline, tetrahydrozoline, oxymetazoline, xylometazoline, and the model compound 2-methyl-2-imidazoline (IZ), were measured by flash-photolysis. The experimental values of these rate constants are on the order of 108–109 M−1 s−1. The reactions with the sulfate radicals proceed by an initial attack on the aromatic rings, which leads to the formation of N-centered radicals of naphazoline and to phenoxyl radicals of the other substrates. The experimental absorption spectra of the intermediates were compared to those obtained from theoretical time-dependent density functional calculations with explicit account for bulk solvent effects.

► The imidazoline derivatives react with SO4− and HPO4−.
► The reactions with SO4− proceed by an initial attack on the aromatic rings.
► N-centered radicals of naphazoline are obtained.
► N-centered radicals and phenoxyl radicals are formed for the other ophthalmic drugs.