Spectral properties and ion dissociation behavior of retinoids I.: Aqueous solutions

Purpose: The spectral properties and ionization behavior of four retinoids: retinoic acid; MTTO; TTNN; and TTNPB, have been determined in aqueous solution to provide a better understanding of their aggregation behavior. Methods: The solubility and ultraviolet absorption spectrum were measured in solutions prepared by equilibration with solid and by dilution of an ethanol solution with buffer. The UV spectral shift was measured as a function of pH to quantify the extent of ionization in 5 and 150 mM NaCl. Fluorescence polarization measurements of TTNN were made. Results: The solubility of the triclinic form of retinoic acid was lower than that of the monoclinic indicating the former is the more stable polymorphic form. For the retinoids, the measured solubility increased with the number of phenyl rings. The wavelengths of maximum absorption and absorptivity of the non-ionized forms of the retinoids systematically changed with chemical structure provided that the preferred molecular conformation was considered. High apparent negative logarithms of the ionization constant, p K a obs , were observed indicating that the retinoids undergo self-association. The titration curves were fit to the Henderson–Hasselbalch relationship, and the p K a obs was dependent on the retinoid concentration in solution. The value of the p K a at low ionic strength was slightly larger that that obtained at high ionic strength. The fluorescent polarization suggested that the aggregation number changes with ionic strength and extent of ionization. Finally, the difference between the observed p K a and the p K a of model compounds was smaller for retinoic acid than for MTTO, TTNPB, and TTNN. Conclusions: All retinoids under study were self-associated giving rise to relatively high values of the apparent p K a. The properties of the aggregates are dependent on the concentration and ionization, and as such, the retinoids probably lack a well-defined aggregation number and critical micelle concentration. The nature of the aggregation for retinoic acid appears distinct from that of the arotinoids, MTTO, TTNPB, and TTNN.