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Influence of Water on Enzymatic Esterification of Racemic Ketoprofen with Ethanol in a Solvent-Free System

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Abstract

The effect of water added in the kinetic resolution of rac-ketoprofen with ethanol catalyzed with Candida antarctica lipase B was investigated under reaction conditions and at a molecular level. The reaction was performed at 45 °C for 24 h with the commercial biocatalyst known as Novozym® 435. The addition of water from 0.5 to 10% v/v to the reaction medium enhances the specific activity (from 2 to 4 μmol mg−1 h−1), enantiomeric ratio E (1 towards 5), enantiomeric factor (EF 0.1 towards 0.5) and the enantiomeric excess towards dexketoprofen (above 50%). At a molecular level, the rate of H/D isotopic exchange of the amide hydrogen of the lipase B of C. antarctica demonstrated that the enzyme exposed to dehydrated ethanol possesses highly flexible sites (45% of the sites are exchanged with a rate of 30 min−1) and the addition of water diminishes the rate of H/D exchange altering the flexibility (the exchange rate falls down to 2.7–0.06 min−1). Additional studies on the secondary structure suggest that the β-sheet structure lead to slowest exchange H-amide sites.

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References

  1. Curiel RV, Katz JD (2013) Pain Med 14:S23–S28

    Article  Google Scholar 

  2. Arfè A, Scotti L, Varas-Lorenzo C, Nicotra F, Zambon A, Kollhorst B, Schink T, Garbe E, Herings R, Straatman H, Schade R, Villa M, Lucchi S, Valkhoff V, Romio S, Thiessard F, Schuemie M, Pariente A, Sturkenboom M, Corrao G (2016) BMJ 354:i4857

    Article  Google Scholar 

  3. Toledo MV, Briand LE (2018) Crit Rev Biotechnol 38:778–800

    Article  CAS  Google Scholar 

  4. Barden J, Derry S, McQuay HJ, Moore RA (2009) Cochrane Database Syst Rev 4:CD007355

    Google Scholar 

  5. Carvalho ACLM, Fonseca TS, Mattos MC, Oliveira MCF, Lemos TLG, Molinari F, Romano D, Serra I (2015) Int J Mol Sci 16:29682–29716

    Article  Google Scholar 

  6. Daiha KG, Angeli R, Oliveira SD, Almeida RV (2015) PLoS ONE 10(6):e0131624

    Article  Google Scholar 

  7. Kumar A, Dhar K, Kanwar SS, Arora PK (2016) Biol Proced Online 18(2):1–11

    Google Scholar 

  8. Adlercreutz P (2013) Chem Soc Rev 42:6406–6436

    Article  CAS  Google Scholar 

  9. Léonard V, Fransson L, Lamare S, Hult K, Graber M (2007) ChemBioChem 8:662–667

    Article  Google Scholar 

  10. Yang L, Dordick JS, Garde S (2004) Biophys J 87:812–821

    Article  CAS  Google Scholar 

  11. Wedberg R, Abildskov J, Peters GH (2012) J Phys Chem B 116:2575–2585

    Article  CAS  Google Scholar 

  12. Park HJ, Choi WJ, Huh EC, Lee EY, Choi CY (1999) J Biosci Bioeng 87:545–547

    Article  CAS  Google Scholar 

  13. De Crescenzo G, Ducret A, Trani M, Lortie R (2000) J Mol Catal B 9:49–56

    Article  Google Scholar 

  14. Chamorro S, Alcántara AR, de la Casa RM, Sinisterra JV, Sánchez-Montero JM (2001) J Mol Catal B 11:939–947

    Article  CAS  Google Scholar 

  15. Di Nardo G, Breitner M, Sadeghi SJ, Castrignanó S, Mei G, Di Venere A, Nicolai E, Allegra P, Gilardi G (2013) PLoS ONE 8:e82118

    Article  Google Scholar 

  16. Busenlehner LS, Armstrong RN (2005) Arch Biochem Biophys 433:34–46

    Article  CAS  Google Scholar 

  17. Foresti ML, Galle M, Ferreira ML, Briand LE (2009) J Chem Technol Biotechnol 84:1461–1473

    Article  CAS  Google Scholar 

  18. Toledo MV, José C, Collins SE, Bonetto RD, Ferreira ML, Briand LE (2012) J Mol Catal B 83:108–119

    Article  CAS  Google Scholar 

  19. Toledo MV, José C, Collins SE, Ferreira ML, Briand LE (2015) J Mol Catal B 118:52–61

    Article  CAS  Google Scholar 

  20. José C, Toledo MV, Nicolás P, Lasalle V, Ferreira ML, Briand LE (2018) Catal Sci Technol 8:3513–3526

    Article  Google Scholar 

  21. José C, Bonetto RD, Gambaro LA, Guauque Torres MP, Foresti ML, Ferreira ML, Briand LE (2011) J Mol Catal B 71:95–107

    Article  Google Scholar 

  22. Llerena-Suster CR, Briand LE, Morcelle SR (2014) Colloid Surf B 121:11–20

    Article  CAS  Google Scholar 

  23. Toledo MV, Llerena Suster CR, Ferreira ML, Collins SE, Briand LE (2017) Catal Sci Technol 7:1953–1964

    Article  CAS  Google Scholar 

  24. Goormaghtigh E, Vigneron L, Scarborough GA, Ruysschaert J-M (1994) J Biol Chem 269:27409–27413

    CAS  PubMed  Google Scholar 

  25. de Jongh HHJ, Goormaghtigh E, Ruysschaert J-M (1995) Biochemistry 34:172–179

    Article  Google Scholar 

  26. Yu S, Fan F, Flores SC, Mei F, Cheng X (2006) Biochemistry 45:15318–15326

    Article  CAS  Google Scholar 

  27. Faber K (2003) Biotransformation in organic chemistry, 5th edn. Springer, Berlin, pp 1–26

    Google Scholar 

  28. López-Belmonte MT, Alcántara AR, Sinisterra JV (1997) J Org Chem 62:1831–1840

    Article  Google Scholar 

  29. Kasche V, Haufler U, Reichman L (1987) Methods Enzymol 136:280–292

    Article  CAS  Google Scholar 

  30. Kasche V (1986) Enzyme Microb Technol 8:4–16

    Article  CAS  Google Scholar 

  31. Chen C-S, Wu S-H, Girdaukas G, Sih CJ (1987) J Am Chem Soc 109:2812–2817

    Article  CAS  Google Scholar 

  32. Rodrigues RC, Ortiz C, Berenguer-Murcia A, Torres R, Fernández-Lafuente R (2013) Chem Soc Rev 42:6290–6307

    Article  CAS  Google Scholar 

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Acknowledgment

The authors acknowledge the financial support provided by Universidad Nacional de La Plata (Project 11 X745), Consejo Nacional de Investigaciones Científicas y Técnicas (Projects PIP 2014-00171CO and PIP 2015-086CO) and Agencia Nacional de Promoción Científica y Tecnológica of Argentina (Project PICT-2014-0497).

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Authors and Affiliations

  1. Centro de Investigación y Desarrollo en Ciencias Aplicadas-Dr. Jorge J. Ronco (CINDECA), Universidad Nacional de La Plata, CONICET, CCT La Plata, Centro Asociado CIC, La Plata, Buenos Aires, Argentina

    María Victoria Toledo & Laura E. Briand

  2. Centro de Investigación de Proteínas Vegetales (CIPROVE), Departamento de Cs. Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata-Centro Asociado CIC), La Plata, Argentina

    Carlos R. Llerena Suster

  3. Departamento de Matemática, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina

    Claudia Ruscitti

  4. Instituto de Desarrollo Tecnológico para la Industria Química INTEC, Universidad Nacional del Litoral, CONICET, Güemes 3450, 3000, Santa Fe, Santa Fe, Argentina

    Sebastián E. Collins

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  1. María Victoria Toledo
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  2. Carlos R. Llerena Suster
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  3. Claudia Ruscitti
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  4. Sebastián E. Collins
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  5. Laura E. Briand
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Correspondence to Laura E. Briand.

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Toledo, M.V., Llerena Suster, C.R., Ruscitti, C. et al. Influence of Water on Enzymatic Esterification of Racemic Ketoprofen with Ethanol in a Solvent-Free System. Top Catal 62, 968–976 (2019). https://doi.org/10.1007/s11244-019-01184-z

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