The substitution effect of functional groups, attached on the aromatic ring of benzoic acid, to the nucleophilic replacement of fullerenic nitronium intermediates by carboxylic acids was demonstrated. The chemistry was utilized for the synthesis of water-soluble polyhydroxylated fullerenes (fullerenols). High reaction product yields (88–90%) of fullerenols were obtained using functional benzoic acids containing one or two electron-withdrawing substituents as nucleophilic reagents. On the contrary, the use of electron-releasing group substituted benzoic acids resulted in a relatively low product yield (38–62%). A competitive superoxide-radical absorbing reaction between DMPO and fullerenol molecules was carried out in a phosphate buffer using an enzymatic system of xanthine/xanthine oxidase for the generation of superoxide radicals. The overall superoxide-radical scavenging efficiency of fullerenols was found to be higher than that of DMPO molecules. Evidence of preferential attack of superoxide radicals toward fullerenol molecules was obtained by a dose-dependent experiment in the presence of a high concentration of DMPO molecules. Complete elimination of DMPO-OH radicals by fullerenols at a dose level of 8.0 mM within a reaction period of 10 min indicated a higher scavenging rate of superoxide radicals for fullerenols than that for DMPO molecules in a concentration of 80 mM.