Prominent inclusion effect of dimethyl-beta-cyclodextrin on photoisomerization of the thromboxane synthetase inhibitor (E)-4-(1-imidazoylmethyl)cinnamic acid.
The direct photoisomerization of (E)-4-(1-imidazoylmethyl)-cinnamic acid (IMC), a thromboxane synthetase inhibitor, to its (Z)-isomer at pH 2.0 was decelerated by beta-cyclodextrin (beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD). The photostationary composition [(Z)-isomer:IMC ratio] was shifted in favor of IMC. These effects were much greater with DM-beta-CyD than with the parent beta-CyD. The quantum yield of the photoisomerization was significantly decreased by complex formation with beta-CyDs, whereas the extinction coefficient of the guest was only slightly decreased. This situation was in sharp contrast to those observed in less polar solvents and suggests that the suppressing mechanism with beta-CyD is different from that with less polar solvent systems. Spectroscopic studies (ultraviolet, circular dichroism, and nuclear magnetic resonance) indicated that IMC is tightly included in an axial mode in the cavity of DM-beta-CyD and that the rotation of the photoreactive site is sterically hindered. The results suggest that the suppressing effect of beta-CyDs on the photoisomerization of IMC results mainly from a steric origin.
Hirayama
F
F
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Utsuki
T
T
Uekama
K
K
Yamasaki
M
M
Harata
K
K
D003505:Cyclodextrins / Q000494:pharmacology*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008689:Methacrylates / Q000737:chemistry* / Q000494:pharmacology; D010777:Photochemistry; D011789:Quantum Theory; D013057:Spectrum Analysis / Q000379:methods; D013237:Stereoisomerism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D003505:Cyclodextrins; D008689:Methacrylates; D013930:Thromboxane-A Synthase; C034364:ozagrel