The photochemical reaction of colchicine to beta- and gamma-lumicolchicine, through a mechanism involving a disrotatory cyclization, is studied by theoretical methods. The energetics of the reaction, including one or two methanol solvent molecules, are studied at the DFT-B3LYP and multireference perturbation levels of theory using the 6-31G(d) basis set. The results show that, in agreement with experimental results, the first excited state of colchicine at similar to 3.6 eV can lead to both beta- and gamma-lumicolchicine, whose energy is about 15 kcal mol(-1) above the colchicine energy. Owing to the high steric tension of the condensed four- and five-atom rings arising from cyclization, the two trans-lumicolchicines are higher in energy (> 60 kcal mol(-1)), and their formation appears much less probable. A partial inclusion of the solvent effects through the addition of two solvent molecules does not alter the general conclusions based on the free energy in the gas phase. The photochemical reaction path is studied by choosing the distance between the two carbon atoms which form the new sigma bond as the leading coordinate of the minimum-energy path of both the ground and the first singlet excited states. The energies are computed by Multi Configurational self-consistent-field calculations on a model molecule, retaining those atoms that presumably play an active role in the reaction. A reasonable mechanism starting from colchicine in the first singlet excited state and leading to gamma-lumicolchicine is proposed. On the contrary, a high-energy transition state is found for trans-lumicolchicines, whose formation, although not strictly forbidden for energetic reasons, appears to be rather improbable.
|Autori:||CACELLI I; M. D'AURIA AND V. VILLANI|
|Titolo:||Theoretical Study of Photochemical Isomerization of Colchicine|
|Anno del prodotto:||2007|
|Digital Object Identifier (DOI):||10.1021/ct600306t|
|Appare nelle tipologie:||1.1 Articolo in rivista|