Solubility of retinoids in water

Spectrophotometric and radioactive techniques were used to measure the water solubility of retinaldehyde, retinol (vitamin A), and retinoic acid under physiological conditions. Hydration decreases the molar extinction coefficient of these substances and shifts their absorption peak bathochromically (10 nm for retinal and approximately 1 nm for the rest). We find their solubility to be about 0.1 microM at room temperature, pH 7.3 (with experimental values being 0.11 microM for retinaldehyde, 0.06 microM for retinol, and 0.21 microM for retinoic acid). To prevent oxidative degradation of retinol, which is the most labile retinoid, our argon-saturated buffer solutions contained physiological levels of ascorbate or alpha-tocopherol. To the best of our knowledge, water solubility of these compounds has not yet been previously reported. Although the measured solubilities are relatively low, they are significant and may account for the movement of retinoids through the aqueous phase as observed by others during exchange with binding proteins and during intervesicular transfer in the absence of binding proteins. Diffusion of uncomplexed retinoids through the aqueous phase can be a major pathway for transport over subcellular distances.