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Published on: August 15, 2016
Complexation study of midazolam hydrochloride with beta-cyclodextrin: NMR spectroscopic study in solution
Syed Mashhood Ali1, Santosh Kumar Upadhyay
1Department of Chemistry, Aligarh Muslim University, Aligarh-202 002, UP, India. smashhoodali@gmail.com
Magnetic Resonance in Chemistry : MRC
|April 3, 2008
Summary
This study confirms the formation of a beta-cyclodextrin-midazolam hydrochloride inclusion complex in water. Beta-cyclodextrin demonstrates chiral differentiation of midazolam hydrochloride during complexation.
Area of Science:
- Supramolecular Chemistry
- Pharmaceutical Sciences
- Analytical Chemistry
Background:
- Midazolam hydrochloride (MDL) is a widely used pharmaceutical agent.
- Beta-cyclodextrin (beta-CD) is a cyclic oligosaccharide known for its ability to form inclusion complexes with various molecules.
- Understanding the interaction between MDL and beta-CD is crucial for potential drug delivery applications.
Purpose of the Study:
- To confirm the formation of an inclusion complex between midazolam hydrochloride and beta-cyclodextrin in aqueous solution.
- To determine the stoichiometry and association constant of the beta-CD-MDL complex.
- To investigate the specific binding interactions and chiral recognition properties during complexation.
Main Methods:
- (1)H Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study the interaction between MDL and beta-CD.
- Two-dimensional Rotating-frame Overhauser Effect SpectroscopY (2D ROESY) was utilized to elucidate the spatial arrangement within the complex.
- Scott's method was applied to determine the stoichiometry of the inclusion complex.
Main Results:
- (1)H NMR and 2D ROESY data confirmed the formation of a beta-CD-MDL inclusion complex in aqueous solution.
- Scott's method revealed a 1:1 stoichiometry for the beta-CD-MDL complex.
- The association constant (K(a)) for the complex was determined to be 108 M(-1).
- 2D ROESY data indicated that the fluorine-substituted aromatic ring of MDL acts as the guest molecule within the beta-CD cavity.
- Induced shifts and signal splitting in MDL's aromatic signals upon complexation demonstrated chiral differentiation by beta-CD.
Conclusions:
- A 1:1 inclusion complex between beta-cyclodextrin and midazolam hydrochloride is formed in aqueous solution.
- The complexation involves the fluorine-substituted aromatic ring of midazolam hydrochloride.
- Beta-cyclodextrin exhibits chiral recognition capabilities towards midazolam hydrochloride, as evidenced by NMR spectral changes.
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