Catalyzed thermal isomerization between previtamin D3 and vitamin D3 via beta-cyclodextrin complexation.
To examine the effect of microenvironments on previtamin D3<==>vitamin D3 isomerization, we have conducted kinetic studies of the reaction in an aqueous solution of beta-cyclodextrin. Our results showed that at 5 degrees C, the forward (k1) and reverse (k2) rate constants for previtamin D3<==>vitamin D3 isomerization were increased by more than 40 and 600 times, respectively, compared with those in n-hexane (k1, 8.65 x 10(-6) versus 1.76 x 10(-7) s-1; k2, 8.48 x 10(-6) versus 1.40 x 10(-8) s-1), the fastest rate of this isomerization ever reported at this temperature. Thermodynamic studies revealed that the equilibrium constant of the reaction was significantly reduced by more than 12-fold when compared to that in n-hexane at 5 degrees C, and the percentage of vitamin D3 at equilibrium was increased as the temperature was increased in beta-cyclodextrin. When complexed with beta-cyclodextrin, the previtamin D3<==>vitamin D3 isomerization became endothermic (delta H zero = 13.05 kJ mol-1) in contrast to being exothermic in other media. We propose that thermodynamically unfavorable cZc conformers of previtamin D3 are stabilized by beta-cyclodextrin, and thus the rate of the isomerization is increased. This conformation-controlled process may play an important role in the modulation of previtamin D3<==>vitamin D3 endocrine system in vivo such as in the sea urchin.
Tian
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XQ
Department of Medicine and Department of Physiology, Boston University Medical Center, Massachusetts 02118, USA.
Holick
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MF
D000818:Animals; D002384:Catalysis; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D012617:Sea Urchins; D013696:Temperature; D013816:Thermodynamics; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D047392:beta-Cyclodextrins; D002762:Cholecalciferol; C025168:previtamin D(3); C031215:betadex