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

Area of Science:

• Biochemistry
• Physical Chemistry

Background:

• The conversion of previtamin D3 to vitamin D3 is a crucial step in the vitamin D endocrine system.
• Understanding the kinetics and thermodynamics of this isomerization is vital for biological and chemical applications.

Purpose of the Study:

• To investigate the influence of microenvironments, specifically beta-cyclodextrin, on the previtamin D3 <=> vitamin D3 isomerization kinetics and thermodynamics.
• To explore the potential role of conformation stabilization in modulating this reaction rate.

Main Methods:

• Kinetic studies were performed to determine the forward (k1) and reverse (k2) rate constants in aqueous beta-cyclodextrin solution.
• Thermodynamic studies were conducted to analyze the equilibrium constant and enthalpy changes.
• Comparisons were made with results obtained in n-hexane.

Main Results:

• The rate constants (k1 and k2) for previtamin D3 <=> vitamin D3 isomerization were dramatically increased in beta-cyclodextrin compared to n-hexane, representing the fastest rates reported at 5°C.
• The equilibrium constant was significantly reduced in beta-cyclodextrin, leading to a higher percentage of vitamin D3 at equilibrium, which increased with temperature.
• The isomerization reaction became endothermic in beta-cyclodextrin, unlike its exothermic nature in other media.

Conclusions:

• Beta-cyclodextrin acts as a microenvironment that significantly enhances the rate of previtamin D3 <=> vitamin D3 isomerization.
• The stabilization of thermodynamically unfavorable cZc conformers of previtamin D3 by beta-cyclodextrin is proposed as the mechanism for the increased reaction rate.
• This conformation-controlled process may be relevant for the in vivo modulation of the vitamin D endocrine system.