Photophysical studies of tin(IV)-protoporphyrin: potential phototoxicity of a chemotherapeutic agent proposed for the prevention of neonatal jaundice.
The strongly light-absorbing metalloporphyrin tin(IV)-protoporphyrin IX (SnPP) is currently being considered as a chemotherapeutic agent for preventing severe hyperbilirubinemia in newborns, a condition usually treated by phototherapy with visible light. To assess the potential phototoxicity of SnPP we studied the photophysics of the drug in aqueous and nonaqueous solutions using laser flash photolysis and pulse radiolysis. Quantum yields for formation of triplet-state excited SnPP were measured, along with triplet lifetimes and extinction coefficients. In addition, we measured quantum yields for the SnPP-photosensitized formation of singlet oxygen in MeO2H and 2H2O containing cetyltrimethylammonium bromide, using a time-resolved luminescence technique. Quantum yields for formation of triplet SnPP from monomeric ground-state SnPP are high (approximately equal to 0.6-0.8), and triplet lifetimes are long (approximately equal to 0.1-0.2 ms). Efficient quenching of triplet SnPP by molecular oxygen was seen with rate constants greater than 10(9) M-1.s-1. SnPP-photosensitized formation of singlet oxygen in aqueous and nonaqueous solvents was confirmed by the detection of the characteristic luminescence at 1270 nm (phi delta = 0.58 in MeO2H). The photophysical parameters and singlet oxygen-sensitizing efficiency of SnPP are similar to those reported for hematoporphyrin and other metal-free porphyrins known to be phototoxic to humans. These observations suggest that cutaneous photosensitivity arising from singlet-oxygen damage is likely to be an undesirable side-effect of SnPP therapy.
Land
E J
EJ
Paterson Institute for Cancer Research, Christie Hospital, Manchester, England.
McDonagh
A F
AF
McGarvey
D J
DJ
Truscott
T G
TG
D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000188:drug therapy*; D007834:Lasers; D008027:Light; D008163:Luminescent Measurements; D046911:Macromolecular Substances; D008665:Metalloporphyrins; D010100:Oxygen; D010777:Photochemistry; D010782:Photolysis; D011166:Porphyrins / Q000633:toxicity*; D011524:Protoporphyrins / Q000627:therapeutic use / Q000633:toxicity*; D011675:Pulse Radiolysis; D012996:Solutions; D013053:Spectrophotometry
D002593:Cetrimonium Compounds; D046911:Macromolecular Substances; D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; D012996:Solutions; C032628:tin protoporphyrin IX; D010100:Oxygen; D000077286:Cetrimonium