Tetramer as efficient structural mode for organizing antioxidative carboxylic acids: The case in inhibiting DNA oxidation.

To overcome the problem on the relationship of antioxidative effect with the branch number in a tetramer, we herein designed a series of antioxidants with pentaerythritol, glycerol, and ethylene glycol as the cores, and gallic, ferulic, caffeic, and p-hydroxybenzoic acids as the antioxidative moieties. In the case of DNA oxidation mediated by 2,2'-azobis(2-amidinopropane hydrochloride, AAPH), it was found that the stoichiometric factor (n) of a carboxylic acid increased rapidly when the acid was esterified with ethylene glycol, glycerol, and pentaerythritol to form a dimer, trimer, and tetramer, respectively. Interestingly, the coefficient in the equation of n∼{branch} ({branch} referred to the number of branches) was higher than one, indicating that the antioxidative effect was enhanced more promptly than the increase of the number of branches. Meanwhile, tetramer exhibited high intercalation effect with DNA strand. Therefore, additionally antioxidative effect was ascribed to the tethering effect resulting from tetrameric structure and strong intercalation with DNA strand generated by tetramer.