title: Course of pH during the formation of amoxicillin by a suspension-to-suspension reaction.
abstract: Amoxicillin can be produced in an enzymatic suspension-to-suspension reaction in which the substrate(s) and product(s) are mainly present as solid particles, while the reaction takes place in the liquid phase. During these suspension-to-suspension reactions different subprocesses take place, such as dissolution/crystallization of substrates and products, enzymatic synthesis of the product(s), and undesired enzymatic hydrolysis of substrates and/or products. All these subprocesses are influenced by pH and also influence the pH because the reactants are weak electrolytes. This paper describes a quantitative model for predicting pH and concentrations of reactants during suspension-to-suspension reactions. The model is based on mass and charge balances, pH-dependent solubilities of the reactants, and enzyme kinetics. For the validation of this model, the kinetically controlled synthesis of amoxicillin from 6-aminopenicillanic acid and D-(p)hydroxyphenylglycine methyl ester was studied. The pH and the dissolved concentrations took a very different course at different initial substrate amounts. This was described quite reasonably by the model. Therefore, the model can be used as a tool to optimize suspension-to-suspension reactions of weak electrolytes.
authors.affiliation: Delft University of Technology, Kluyver Laboratory for Biotechnology, Julianalaan 67, NL-2628 BC, Delft, The Netherlands
authors.initials: MB
authors.lastname: Diender
authors.initials: AJ
authors.lastname: Straathof
authors.lastname: van der Does T
authors.initials: M
authors.lastname: Zomerdijk
authors.initials: JJ
authors.lastname: Heijnen