Structural Analysis of Crystalline R(+)-α-Lipoic Acid-α-cyclodextrin Complex Based on Microscopic and Spectroscopic Studies.
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.
Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan. naoko.ikuta@people.kobe-u.ac.jp.
Naoko
N
Ikuta
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. tkendo@staff.kanazawa-u.ac.jp.
Takatsugu
T
Endo
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. hsmst14@gmail.com.
Shota
S
Hosomi
Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan. tektites5@gmail.com.
Keita
K
Setou
Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan. yfd44023@nifty.com.
Shiori
S
Tanaka
Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan. noriko30@dpc.agu.ac.jp.
Noriko
N
Ogawa
Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan. hiromitu@dpc.agu.ac.jp.
Hiromitsu
H
Yamamoto
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. peridot@staff.kanazawa-u.ac.jp.
Tomoyuki
T
Mizukami
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. ultrasa@staff.kanazawa-u.ac.jp.
Shoji
S
Arai
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. mokuno@staff.kanazawa-u.ac.jp.
Masayuki
M
Okuno
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. ktkenji@staff.kanazawa-u.ac.jp.
Kenji
K
Takahashi
Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan. keiji.terao@cyclochem.com.|CycloChem Bio Co., Ltd., Kobe 650-0047, Japan. keiji.terao@cyclochem.com.
Keiji
K
Terao
College of Science and Engineering, Kanazawa University, Kanazawa 920-1192, Japan. s-matsugoh@se.kanazawa-u.ac.jp.
Seiichi
S
Matsugo
D003460:Crystallization; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D008063:Thioctic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D047391:alpha-Cyclodextrins; D008063:Thioctic Acid
ATR/FT-IR; cyclodextrin; lipoic acid; microscopic Raman; solid-state NMR