Solid–Liquid Equilibrium of Substrates and Products of the Enzymatic Synthesis of Ampicillin

Abstract

The solid–liquid equilibrium of precursors and products of the enzymatic synthesis of ampicillin (AMP) [6-aminopencillanic acid (6-APA) and D( )phenylglycine (PG)] was investigated at different temperatures (283–298 K) and pHs (5.5–7.5). Solubility data were obtained using an analytical methodology. Equilibrium dissociation constants were experimentally measured at several temperatures for AMP, 6-APA, PG, and D( )phenylglycine methyl ester. A model based on the simplified perturbed hard sphere theory proposed by Khoshkbarchi and Vera (Ind Eng Chem Res. 1996;35:4319- 4327) was fitted against solubility data. The model could describe the water solubility behavior for AMP and PG as function of pH and temperature, but a bias was observed when fitting the model to the solubility of 6-APA. VVC 2009 American Institute of Chemical Engineers AIChE J, 56: 1578–1583, 2010