SOLUBILITY OF N-(BENZYLOXYCARBONYL)-L-ASPARTYL-L-PHENYLALANINE METHYL-ESTER FORMING A COMPLEX WITH L-PHENYLALANINE METHYL-ESTER IN AQUEOUS SYSTEM

The solubility of N-(benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-APM) was studied in an aqueous system with coexisting L-phenylalanine methyl ester (L-Phe-OMe). It was found that the Z-APM solubility shows very complicated behavior. Under acidic pH condition (pH < 3.5), pure Z-APM was precipitated and the solubility increased uniformly with increasing pH and L-Phe-OMe concentration. Under moderate pH condition (4.5 < pH < 8), Z-APM was precipitated with L-Phe-OMe, forming a complex of Z-APM.L-Phe-OMe. The solubility varied with the pH following a U-shaped curve and decreased with increasing L-Phe-OMe concentration at the same pH. The pH value at the transient point from pure Z-APM precipitation to Z-APM-L-Phe-OMe precipitation shifted toward acidic pH with increasing L-Phe-OMe concentration. From the experimental results it was assumed that the Z-APM.L-Phe-OMe complex was not only formed by ionic bond. An equilibrium model of the precipitation considering the formation of complex was proposed that well explains the complicated behavior of the solubility.