Investigation of the thermal isomerization of 1α,25-dihydroxycholecalciferol by nuclear magnetic resonance spectroscopy

This investigation of the kinetics and thermodynamics of the thermal isomerization reaction of 1α,25-dihydroxycholecalciferol, the physiologically active metabolite of vitamin D₃, is based on the simultaneous determinations of 1α,25-(OH)₂D₃ and its previtamin analog by nuclear magnetic resonance spectroscopy which distinguishes these compounds from possible impurities. The kinetics at different temperatures are used to obtain the activation parameters for the sigmatropic [1,7] thermal interconversion process which is shown to be compatible with a reaction that is unimolecular and concerted. The nature of the transition state of the activated complex, the reaction energetics, and the relative stabilities of 1α,25-(OH)₂D₃ and vitamin D₃ are discussed.