Model systems for metabolism studies. Biomimetic oxidation of acetaminophen and ellipticine derivatives with water-soluble metalloporphyrins associated to potassium monopersulfate.
Some original water-soluble metalloporphyrins/KHSO5 systems were developed to mimic the metabolic biooxidation of drugs. Oxidation of acetaminophen and various ellipticine derivatives were used as model reactions. Oxidative products (mainly quinone-imine structures) were obtained in good yield after 2 min of reaction, for a catalyst/substrate ratio of 0.04. Iron(III) derivative of tetrasodium meso-tetrakis(p-sulfonatophenyl)porphyrin and manganese(III) derivative of tetraacetate meso-tetrakis(4-N-methyl-pyridiniumyl)-porphyrin were the best catalysts for the oxidation of acetaminophen and ellipticine compounds, respectively. At low catalyst concentration, initial turnover rates could rise up to 8 catalytic cycles/sec. In some conditions, these catalytic systems are nearly as efficient as horseradish peroxidase/H2O2. They might have a real future as oxidation catalysts, in complement to the use of purified monooxygenase and peroxidases, to predict the possible in vivo oxidative metabolite pathways.
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Toulouse, France.
J
J
Bernadou
M
M
Bonnafous
G
G
Labat
P
P
Loiseau
B
B
Meunier
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D004611:Ellipticines / Q000378:metabolism*; D006735:Horseradish Peroxidase; D008665:Metalloporphyrins / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D011188:Potassium / Q000378:metabolism; D017680:Potassium Compounds; D013056:Spectrophotometry, Ultraviolet; D013431:Sulfates / Q000378:metabolism*
D004611:Ellipticines; D008665:Metalloporphyrins; D017680:Potassium Compounds; D013431:Sulfates; C034192:ellipticine; D000082:Acetaminophen; C009007:potassium persulfate; D006735:Horseradish Peroxidase; D011188:Potassium