Catalyzed thermal isomerization between previtamin D3 and vitamin D3 via β-cyclodextrin complexation

Abstract

To examine the effect of microenviroments on previtamin D3 ⇆ vitamin D3 isomerization, 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 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 °C, and the percentage of vitamin D3 at equilibrium was increased as the temperature was increased in β-cyclodextrin. When complexed with β-cyclodextrin, the previtamin D3 ⇆ vitamin D3 isomerization became endothermic (ΔH° = 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 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 D3 endocrine system in vivo such as in the sea urchin.