Quantitative assessment of the negative catalytic effects of a cationic surfactant myristyl-γ-picolinium chloride on the specific-acid catalyzed epimerization of 15(S)-15-methyl prostaglandin F2α

The specific-acid catalyzed epimerization of 15(S)-15-methyl PGF_2α was found to be significantly inhibited in the presence of a cationic surfactant, myristyl-γ-picolinium chloride, at pH 2.5 and 25°C. The micellar inhibition observed is attributed to electrostatic repulsion between hydronium ion and the cationic polar heads of the micellar phase. As expected, at a given concentration of prostaglandin, the observed rate decreased as the surfactant concentration increased. When the concentration of prostaglandin was in the order of 7 × 10⁻² mg/ml (2 × 10⁻⁷M), the observed epimerization rate in a 1.0% surfactant solution was found to be approximately 120 times slower than that observed in the absence of surfactant. A quantitative analysis showed that the epimerization rate constant in the micellar phase is in the order of 6 × 10⁻⁷ s⁻¹ (cf. 2 × 10⁻⁴ s⁻¹ in the absence of the surfactant).However, the extent of micellar inhibition decreased as the initial concentration of prostaglandin increased in a series of solutions containing a constant amount of the surfactant. In order to quantitatively interpret this result, the apparent partition coefficient (ψm) of the prostaglandin between the micellar phase and the aqueous bulk phase was determined using a partitioning technique. Heterogeneity of the binding sites was detected in the analysis of ψm using the Scatchard equation.The primary binding sites are postulated to occur by a short penetration of prostaglandin molecules in the palisade layer. The secondary binding sites can be provided by either a simple adsorption process of prostaglandin onto the surface of micelles or the formation of mixed micelles. Although the primary binding sites show approximately 75-fold greater affinity towards the prostaglandin than the secondary binding sites, the number of available sites of the latter is approximately 25 times greater than that of the former. It is proposed that the Scatchard equation be used in the quantitative analysis of the effects of the substrate concentration at a constant surfactant concentration upon the observed micellar catalysis, a subject which has been unjustifiably neglected in the past.