Catalyzed Thermal Isomerization between Previtamin D3 and Vitamin D3 via β-Cyclodextrin Complexation (*)

To examine the effect of microenviroments on previtamin D3 ⇌ vitamin D3isomerization, we have conducted kinetic studies of the reaction in an aqueous solution of β-cyclodextrin. Our results showed that at 5°C, the forward (k1) and reverse (k2) rate constants for previtamin D3⇌ vitamin D3isomerization were increased by more than 40 and 600 times, respectively, compared with those in n-hexane (k1, 8.65 × 10−6versus 1.76 × 10−7s−1; k2, 8.48 × 10−6versus 1.40 × 10−8s−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°C, and the percentage of vitamin D3at equilibrium was increased as the temperature was increased in β-cyclodextrin. When complexed with β-cyclodextrin, the previtamin D3⇌ vitamin D3isomerization became endothermic (Δ Ho= 13.05 kJ mol−1) in contrast to being exothermic in other media. We propose that thermodynamically unfavorable cZc conformers of previtamin D3are stabilized by β-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 D3endocrine system in vivo such as in the sea urchin.