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

International Journal of Molecular Sciences

Naoko Ikuta²  Takatsugu Endo¹  Shota Hosomi¹  Keita Setou³  Shiori Tanaka³  Noriko Ogawa³  Hiromitsu Yamamoto³  Tomoyuki Mizukami¹  Shoji Arai¹  Masayuki Okuno¹  Kenji Takahashi¹  Keiji Terao²  Seiichi Matsugo¹ 

[1] College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan; E-Mails:;Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan; E-Mails:;Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan; E-Mails:

关键词: cyclodextrin;    lipoic acid;    ATR/FT-IR;    microscopic Raman;    solid-state NMR;   

DOI  :  10.3390/ijms161024614

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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