Uncoupling behavior of the 4-phenylcoumarins in spinach chloroplasts: Structure-activity relationships

4-Phenylcoumarins isolated from Exostema caribaeum and Hintonia latiflora (Rubiaceae) and some semisynthetic derivatives acted as uncouplers in spinach chloroplasts. The glycoside 5-O-beta-D-glucopyranosyl-7-methoxy-3',4'-dihydroxy (3), 5,7,3',4'-tetrahydroxy-4-phenyl-coumarin (1a), and 7-methoxy-5,3',4'-trihydroxy-4-phenylcoumarin (2a) inhibited ATP synthesis and proton uptake. On the other hand, basal and phosphorylating electron transport were enhanced by these compounds. The light-activated Mg2+-ATPase was slightly stimulated by coumarins 1a and 2a. In addition, at alkaline pH compound 1a stimulated the basal electron flow from water to methylviologen, but at the pH range from 6.0 to 7.5 the coumarin did not have any enhancing effect. Compound 1a, which possesses four free phenolic hydroxyl groups, was the most active uncoupler agent. Methylation (2b, 4), acetylation (2a), or glycosylation (1-3) of the phenolic groups at C-3', C-4', and C-5 resulted in a reduction or loss of the uncoupling activity. Therefore, the phenolate anions may be the active form responsible for the uncoupling behavior of 4-phenylcoumarins.