title: Theoretical study of ibuprofen phototoxicity.
abstract: The photochemical properties and degradation of the common nonsteroid anti-inflammatory drug ibuprofen is studied by means of hybrid density functional theory. Computed energies and properties of various species show that the deprotonated form dominates at physiological pH, and that the species will not be able to decarboxylate from a singlet excited state. Instead, decarboxylation will occur, with very high efficiency, provided the deprotonated compound can undergo intersystem crossing from an excited singlet to its excited triplet state. In the triplet state, the C-C bond connecting the carboxyl group is elongated, and the CO2 moiety detaches with a free energy barrier of less than 0.5 kcal/mol. Depending on the local environment, the decarboxylated product can then either be quenched through intersystem crossing (involving the possible formation of singlet oxygen) and protonation, or serve as an efficient source for superoxide anions and the formation of a peroxyl radical that will initiate lipid peroxidation.
authors.affiliation: Department of Natural Sciences, Orebro University, 701 82 Orebro, Sweden.
authors.forename: Klefah A K
authors.initials: KA
authors.lastname: Musa
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003653:Decarboxylation; D017484:Dermatitis, Phototoxic / Q000503:physiopathology*; D007052:Ibuprofen / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D015227:Lipid Peroxidation; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010777:Photochemistry; D011522:Protons; D017382:Reactive Oxygen Species; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011522:Protons; D017382:Reactive Oxygen Species; D007052:Ibuprofen