PubChem reports that both vitamin D2 and D3 are insoluble in water . The results here suggest that while vitamin D2 and D3 can hydrogen bond favorably with water, the cavity formation is highly unfavorable, and that is a reason for the poor aqueous solubility. The difference in the total solvation-free energy between two solvents is equivalent to the transfer-free energy and is directly related to the log partition coefficient or log relative solubility. Using the uESE results, comparing water and ethanol, the results suggest the solubility is 10 11 and 10 8 times larger in methanol for vitamin D2 and D3, respectively. Comparing water and cyclohexane, the results suggest the solubility is 10 14 and 10 10 times larger in cyclohexane methanol for vitamin D2 and D3, respectively.