An exploratory theoretical elucidation on the peroxyl-radical-scavenging mechanism and structure–activity relationship of nonsteroidal anti-inflammatory drugs

The peroxyl-radical-scavenging mechanism of some nonsteroidal anti-inflammatory drugs (NSAIDs), namely tolmetin, ketorolac, indomethacin, acemetacin, and oxaprozin, is clarified by combined density functional theory (DFT) calculations. It is revealed that H-atom-abstraction rather than electron transfer reaction is involved in the radical-scavenging process of these NSAIDs in polar aqueous solution. This seems contrary to the common viewpoint that the latter is predominant in polar media. The calculated results also show that H-atom at C(β) or C(γ) position is readily to be abstracted, and the lowest C–H bond dissociation enthalpy (BDE) can qualitatively account for the activity difference for the five NSAIDs.