Steroid solubility studies with aqueous solutions of urea and ureides

Abstract

Aqueous solutions of urea, 1-acetyl-3-methyl-urea and 1,3-dimethyl urea increase the water solubility of testosterone and some related steroids if the 17-hydroxyl group of the steroid is free.

The heats of solution of testosterone in water and 2 M, 4 M, 6 M, and 8 M urea are essentially the same (about 4.3 kcal mol⁻¹ degree⁻¹) in the 15 °–35 °C temperature range. The free energy of transfer of testosterone from water to aqueous urea is independent of temperature for a given urea concentration. The ultraviolet absorption maximum as well as the molecular extinction coefficient for testosterone is essentially the same in 8 M urea and in water. These data are interpreted as indicating that testosterone is solubilized in aqueous urea by a combination of urea interaction with with a 17-polar group and an environment which can accommodate the nonpolar portions of the steroid. The spectral evidence suggests that with 8M urea the Δ⁴-3-keto group of the A-ring behaves as if still essentially in an aqueous environment.