Nifedipine and nitrendipine reactivity toward singlet oxygen

Abstract

The ability to generate singlet molecular oxygen, O-2((1)Delta(g)), and the scavenging activity of two well-known 1,4-dihydropyridines (1,4-DHPs) such as nifedipine (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 O-2((1)Delta(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 x 10(5) M-1 s(-1) in dioxane to 93.0 x 10(5) 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 O-2((1)Delta(g)), but it is aless efficient scavengerof this species. Rate constants range from 1.88 x 10(5) M-1 S-1 in ethyl acetate to 15.8 x 10(5) M-1 S-1 in NN-dimethylacetamide, the reactive channel being the main O-2(Delta(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.