In this paper, the synthesis and free-radical scavenging capacity of novel calix[4]arene-based cluster of paracetamol was reported. The phenolic structures of acetaminophen and calix[4]arene prompted us for designing a synthetic route for calix[4]arene-based cyclic tetramer of paracetamol. The present chalice-shaped cluster is the first example of calixarene/acetaminophen hybrid and paracetamol can be considered as ¼ of the synthetic cyclic tetramer. Free-radical scavenging tests were determined by the 2,2-diphenyl-1-picrylhydrazyl radical in methanol. The results of antiradical-testing showed the enhanced free-radical scavenging capacity (~ 10-fold) for the prepared chaliced-shaped cluster with respect to the corresponding single therapeutic drug unit (acetaminophen). It is maybe attributed to the multivalency, spatial preorganization, and synergistic effect of four impacted drug units in the cluster structure (clustering effect).
Keywords: Acetaminophen; Antiradical; Calixarene; Cluster; Paracetamol; Radical scavenger.