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Updated: Sep 28, 2026

The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Enzymatic synthesis of beta-lactam antibiotics via direct condensation
R V Ulijn1, L De Martin, P J Halling
1Department of Pure and Applied Chemistry, Thomas Graham Building, 295 Cathedral Street, G1 1XL Glasgow, Scotland, UK. rein.ulijn@ed.ac.uk
Abstract:
In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic beta-lactam antibiotics is studied. As an example of the first type, penicillin G was produced in good yield (160 mmol kg(-1)) directly from the free acid and amine aqueous substrate suspension, where the synthesis product precipitated. Such a precipitation driven synthesis via direct reversal of the hydrolytic reaction is thermodynamically unfavourable for zwitterionic beta-lactam antibiotics, such as amoxicillin. In this paper, a novel method is suggested to help favour precipitation of (poorly soluble) product salts by deliberate addition of certain counter-ions. After screening a number of different counter-ions, it was found that the amoxicillin anion forms a poorly soluble salt with Zn(2+). Despite increased beta-lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO(4) present the synthetic yield could be increased at least 30-fold.
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