Determination of preferred conformations of ibuprofen in chloroform by 2D NOE spectroscopy

I A Khodov; S V Efimov; V V Klochkov; G A Alper; L A E Batista de Carvalho

doi:10.1016/j.ejps.2014.08.005

Determination of preferred conformations of ibuprofen in chloroform by 2D NOE spectroscopy

Eur J Pharm Sci. 2014 Dec 18:65:65-73. doi: 10.1016/j.ejps.2014.08.005. Epub 2014 Sep 16.

Authors

I A Khodov¹, S V Efimov², V V Klochkov², G A Alper³, L A E Batista de Carvalho⁴

Affiliations

¹ Institute of Physics, Kazan Federal University, Kremlevskaya St. 18, Kazan 420008, Russia; G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Akademicheskaya St. 1, Ivanovo 153045, Russia. Electronic address: Ilya.Khodov@gmail.com.
² Institute of Physics, Kazan Federal University, Kremlevskaya St. 18, Kazan 420008, Russia.
³ G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Akademicheskaya St. 1, Ivanovo 153045, Russia.
⁴ Molecular Physical Chemistry R&D Unit, University of Coimbra, Coimbra 3004-535, Portugal.

PMID: 25220492
DOI: 10.1016/j.ejps.2014.08.005

Abstract

Solution of an anti-inflammatory drug ibuprofen ((RS)-2-(4-isobutylphenyl) propionic acid) in chloroform was studied by nuclear magnetic resonance spectroscopy. A set of 2D NOESY spectra was analyzed in order to obtain atom-atom distances. Since ibuprofen is known to exist as an ensemble of different conformations, these distances are averaged over the ensemble. To compare experimental and calculated distances, three models of averaging were concerned. Our data allowed to determine the dominant conformers of ibuprofen dissolved in chloroform. The population of conformers in the saturated solution leads to a certain crystal morphology formed within the nucleation process. Observed and calculated (13)C chemical shifts (at the DFT/B3LYP/6-311+G(2d,p) level) were in good agreement.

Keywords: 2D NOESY; Conformation; Ibuprofen (PubChem CID: 3672); NMR.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chloroform / chemistry*
Ibuprofen / chemistry*
Molecular Conformation
Solutions / chemistry
Spectrum Analysis / methods

Substances

Solutions
Chloroform
Ibuprofen