NMR and DFT Calculation Study on Structures of 2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione (NTBC) and Its Two Metabolites Isolated from Urine of Patients Suffering from Tyrosinemia Type I.

Adam Gryff-Keller (1) , Przemysław Szczeciński (1) , Anna Kraska-Dziadecka (1)

1 Faculty of Chemistry

2-[2-Nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione (NTBC) is an active component of nitisinone, a medicine against tyrosinemia type I. Using 1H, 13C and 19F NMR spectroscopy it has been found that in urine of patients treated with nitisinone two compounds possessing CF3 group are always present. They have been isolated by TLC technique and identified as 4-hydroxy-2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione and 5-hydroxy-2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione, the latter being previously unknown. The constitution, tautomerism and stereochemistry of these compounds have been thoroughly investigated using 1H and 13C NMR spectroscopy supported by theoretical calculations. Molecular structures have been optimized using density functional theory (DFT) with PBE1PBE functional and 6-31G* basis set. In NMR parameter calculations the larger 6-311++G(2d,p) basis set has been used. At both calculation stages the polarizable continuum model of the solvent has been employed.

Mots clés: Physical Sciences

Adam Gryff-Keller, Przemysław Szczeciński, Anna Kraska-Dziadecka. NMR and DFT Calculation Study on Structures of 2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione (NTBC) and Its Two Metabolites Isolated from Urine of Patients Suffering from Tyrosinemia Type I.. Journal of Physical Organic Chemistry, 2010, 24 (3), pp.249. ⟨10.1002/poc.1736⟩. ⟨hal-00599806⟩