Exposing Hidden Conformations of Carbamazepine Appearing Due to Interaction With the Solid Phase by 2D 1H-15N HMBC NMR Spectroscopy

Ilya Khodov; Sergey Efimov; Michael Krestyaninov; Michael Kiselev

doi:10.1016/j.xphs.2021.01.001

Exposing Hidden Conformations of Carbamazepine Appearing Due to Interaction With the Solid Phase by 2D ¹H-¹⁵N HMBC NMR Spectroscopy

J Pharm Sci. 2021 Apr;110(4):1533-1539. doi: 10.1016/j.xphs.2021.01.001. Epub 2021 Jan 7.

Authors

Ilya Khodov¹, Sergey Efimov², Michael Krestyaninov³, Michael Kiselev³

Affiliations

¹ G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo, 193045 Russia. Electronic address: iakh@isc-ras.ru.
² Institute of Physics, Kazan Federal University, Kazan, 420008 Russia.
³ G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo, 193045 Russia.

PMID: 33421434
DOI: 10.1016/j.xphs.2021.01.001

Abstract

Two-dimensional ¹H-¹⁵N HMBC NMR spectra of the well-known anticonvulsant carbamazepine dissolved in different organic solvents, recorded on an NMR spectrometer prove the existence of hidden conformers in saturated solutions. Obtained conformer distribution arises due to the presence of the solid phase in saturated solution. A weak influence of ring currents was revealed for different molecular conformations of carbamazepine dissolved in a saturated solution, which provides a simple approach to discovering hidden conformations. Hidden conformers were found in three different solvents: dimethyl sulfoxide, chloroform, and dichloromethane.

Keywords: Drug design; Nuclear magnetic resonance (NMR) spectroscopy; Polymorph(s); Spectroscopy; Structure.

Publication types

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

MeSH terms

Carbamazepine*
Chloroform*
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Conformation

Substances

Carbamazepine
Chloroform