Conformation of six fentanyls revisited

Autor: Piotr F. J. Lipiński, Małgorzata Jarończyk, Jan Cz. Dobrowolski, Joanna Sadlej, Sławomir Ostrowski
Rok vydání: 2016
Předmět:
Zdroj: Computational and Theoretical Chemistry. 1086:18-24
ISSN: 2210-271X
Popis: Conformation of fentanyl and its five derivatives was studied at the B3LYP/6-31G ∗∗ level. Two stereoisomers for α-methyl-β-hydroxy fentanyl and four for the ohmefentanyl were taken into account. Conformation in the gas phase and water, simulated using the IEF-PCM and SMD implicit models of solvents, was independently optimized using 27 starting structures resulted from rotations about the most important three torsion angles. The role of the Grimme’s D3 correction for the dispersion forces was additionally considered for each medium. The correction appeared to influence more the gas phase than water dissolved structures. Moreover, the correction influences more the conformations of N-phenylpropionamide group than those of the modified phenylethyl substituent. In water solution simulated by the IEF-PCM and SMD solvation models, the conformers connected to the phenylethyl moiety, are substantially different only for the two derivatives, for which indications coming from different computational variants are the most vague. However, for the conformers connected to the N-phenylpropionamide group, the IEF-PCM model favors the t conformation for three derivatives while SMD prefers sum of the g + and g − conformations for the other three derivatives. For the ohmefentanyl stereoisomers, irrespectively, the solvation or presence of the D3 correction, all the methods concordingly predict the N-phenylpropionamide group conformation twisted by either −120° or to 120°.
Databáze: OpenAIRE
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