Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies

Int J Mol Sci. 2015 Oct 16;16(10):24614-28. doi: 10.3390/ijms161024614.

Abstract

R(+)-α-lipoic acid (RALA) is a naturally-occurring substance, and its protein-bound form plays significant role in the energy metabolism in the mitochondria. RALA is vulnerable to a variety of physical stimuli, including heat and UV light, which prompted us to study the stability of its complexes with cyclodextrins (CDs). In this study, we have prepared and purified a crystalline RALA-αCD complex and evaluated its properties in the solid state. The results of ¹H NMR and PXRD analyses indicated that the crystalline RALA-αCD complex is a channel type complex with a molar ratio of 2:3 (RALA:α-CD). Attenuated total reflection/Fourier transform infrared analysis of the complex showed the shift of the C=O stretching vibration of RALA due to the formation of the RALA-αCD complex. Raman spectroscopic analysis revealed the significant weakness of the S-S and C-S stretching vibrations of RALA in the RALA-αCD complex implying that the dithiolane ring of RALA is almost enclosed in glucose ring of α-CD. Extent of this effect was dependent on the direction of the excitation laser to the hexagonal morphology of the crystal. Solid-state NMR analysis allowed for the chemical shift of the C=O peak to be precisely determined. These results suggested that RALA was positioned in the α-CD cavity with its 1,2-dithiolane ring orientated perpendicular to the plane of the α-CD ring.

Keywords: ATR/FT-IR; cyclodextrin; lipoic acid; microscopic Raman; solid-state NMR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallization
  • Magnetic Resonance Spectroscopy
  • Microscopy, Electron, Scanning
  • Spectroscopy, Fourier Transform Infrared
  • Spectrum Analysis, Raman
  • Thioctic Acid / chemistry*
  • X-Ray Diffraction
  • alpha-Cyclodextrins / chemistry*

Substances

  • alpha-Cyclodextrins
  • Thioctic Acid