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Ionization constants and solubility of compounds involved in enzymatic synthesis of aminopenicillins and aminocephalosporins

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Abstract

The article deals with experimental determination of ionization constants and solubility for the compounds (target products, initial β-lactams, acylating agents and by-products) involved in enzymatic synthesis of some therapeutically used aminopenicillins and aminocephalosporins, namely ampicillin, amoxicillin, cephalexin, cephadroxil, cephaloglycin, cefaclor, cefprozil, cefatrizine. Methodology of investigations and the evaluation of experimental data for the determination of ionization constants and solubility of the different type electrolytes are presented. Applications of the methods based on acid–base potentiometric titration and on determination of solubility–pH dependence of assayed substances are discussed. The original data on ionization constants and solubility of amoxicillin, cefprozil, cefatrizine, cephadroxil and initial β-lactams for production of cefaclor, cefprozil and cefatrizine, as well as solubility of by-product d-(−)-p-hydroxyphenylglycine are presented. Experimentally determined parameters and constants available in the literature for all abovementioned aminopenicillins and aminocephalosporins are collected. These data might be used for choice of the conditions of both processes: the enzymatic synthesis and the isolation of the product from reaction mixture.

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Notes

  1. Correction of total titrant consumption on the volume that was spent specially for changing concentration of free H+ ions to adjust pH in the system is necessary under titration at pH values lower than 4.

  2. Correction of total titrant consumption on the volume that was spent specially for changing concentration of free H+ ions to adjust pH in the system is necessary under titration at pH values higher than 10.

  3. The characteristic solubility of an electrolyte is considered as solubility of its individual electro-neutral form that is zwitterionic form of amino acid or uncharged form of mono-carboxylic acid or monoamine.

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Acknowledgments

The authors are grateful to Sichuan Industrial Institute of Antibiotics (China) for support of the work concerning study of the parameters for compounds involved in cefprozil and cefatrizine synthesis.

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Authors and Affiliations

  1. State Research Institute of Genetics and Selection of Industrial Microorganisms (GosNIIgenetika), 1st Dorozhny proezd, 1, Moscow, 117545, Russia

    V. B. Kurochkina, A. V. Sklyarenko, J. E. Satarova & S. V. Yarotsky

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  1. V. B. Kurochkina
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  2. A. V. Sklyarenko
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  3. J. E. Satarova
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  4. S. V. Yarotsky
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Correspondence to A. V. Sklyarenko.

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Kurochkina, V.B., Sklyarenko, A.V., Satarova, J.E. et al. Ionization constants and solubility of compounds involved in enzymatic synthesis of aminopenicillins and aminocephalosporins. Bioprocess Biosyst Eng 34, 1103–1117 (2011). https://doi.org/10.1007/s00449-011-0560-9

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  • DOI: https://doi.org/10.1007/s00449-011-0560-9

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