Conformational, Spectroscopic, and Molecular Dynamics DFT Study of Precursors for New Potential Antibacterial Fluoroquinolone Drugs

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• 作者：Sandra Dorot铆kov谩 ; Krist铆na Plevov谩 ; Luk谩拧 Bu膷insk媒 ; Michal Mal膷ek ; Peter Herich ; Lenka Kuckov谩 ; Miroslava Bobeni膷ov谩 ; Stanislava 艩oralov谩 ; Jozef Ko啪铆拧ek ; Marek Fronc ; Viktor Milata ; Dana Dvoranov谩
• 刊名：Journal of Physical Chemistry A
• 出版年：2014
• 出版时间：October 9, 2014
• 年：2014
• 卷：118
• 期：40
• 页码：9540-9551
• 全文大小：496K
• ISSN：1520-5215

文摘

Biological activity, functionality, and synthesis of (fluoro)quinolones is closely related to their precursors (for instance 3-fluoroanilinoethylene derivatives) (i.e., their functional groups, conformational behavior, and/or electronic structure). Herein, the theoretical study of 3-fluoroanilinoethylene derivatives is presented. Impact of substituents (acetyl, methyl ester, and ethyl ester) on the conformational analysis and the spectral behavior is investigated. The B3LYP/6-311++G** computational protocol is utilized. It is found that the intramolecular hydrogen bond N鈥揌路路路O is responsible for the energetic preference of anti (a) conformer (anti position of 3-fluoroanilino group with respect to the C鈺怌 double bond). The Boltzmann ratios of the conformers are related to the differences of the particular dipole moments and/or their dependence on the solvent polarity. The studied acetyl, ethyl ester, and methyl ester substituted fluoroquinolone precursors prefer in the solvent either EZa, ZZa, or both conformers equally, respectively. In order to understand the degree of freedom of rotation of the trans ethyl ester group, B3LYP/6-311G** molecular dynamic simulations were carried out. Vibrational frequencies, electron transitions, as well as NMR spectra are analyzed with respect to conformational analysis, including the effect of the substituent. X-ray structures of the precursors are presented and compared with the results of the conformational analysis.