title: An exploratory theoretical elucidation on the peroxyl-radical-scavenging mechanism and structure-activity relationship of nonsteroidal anti-inflammatory drugs.
abstract: 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(beta) or C(gamma) 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.
authors.affiliation: State Key Lab for Structural Chemistry of Unstable and Stable Species, Center for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Lan-fen
authors.initials: LF
authors.lastname: Wang
authors.forename: Yu-guang
authors.initials: YG
authors.lastname: Song
authors.forename: Xiu-feng
authors.initials: XF
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010545:Peroxides / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010545:Peroxides; C049375:perhydroxyl radical