Nifedipine and nitrendipine reactivity toward singlet oxygen

The ability to generate singlet molecular oxygen, O₂ (¹Δ_g), and the scavenging activity of two well-known 1,4-dihydropyridines (1,4-DHPs) such asnifedipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine-dicarboxylic acid dimethyl ester) and nitrendipine (1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxylic acid ethyl methyl ester) is assessed. Results show that nifedipine does not generate O₂(¹Δ_g) under our experimental conditions. In contrast, this 1,4-dihydropyridine behaves as a good scavenger of excited oxygen, mainly via physical deactivation with values of the total rate constant ranging from 20.8 × 10⁵M^-1 s^-1 in dioxane to 93.0 × 10⁵ M^-1 s^-1 in propylencarbonate. The less favored reactive pathway generates a photooxidation product, which has been isolated and identified by GC-MS as the nitropyridine derivative. Voltammetric experiments also confirm the generation of this oxidation product. On the other hand, nitrendipine yields O₂(¹Δ_g), but it is a less efficient scavenger of this species. Rate constants range from 1.88 × 10⁵ M^-1 s^-1 in ethyl acetate to 15.8 × 10⁵ M^-1 s^-1 in N,N-dimethylacetamide, the reactive channel being the main O₂(Δ_g) deactivation pathway. Dependence on solvent microscopic parameters of the total rate constant for the reaction between singlet oxygen and 1,4-DHPs permits us to propose a mechanism involving a perepoxide-like encounter complex in the first step of the reaction path.