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.
Bernadou
J
J
Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, Toulouse, France.
Bonnafous
M
M
Labat
G
G
Loiseau
P
P
Meunier
B
B
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