The Effect of Temperature on the Enantioselectivity of Lipase-Catalyzed Reactions; Case Study: Isopropylidene Glycerol Reaction

Year 2022, Volume: 5 Issue: 1, 29 - 38, 31.05.2022

Adnan Aydemir

Abstract

Commercial lipase (triacylglycerol lipase (EC 3.1.1.3) of Burkholderia cepacia (40 U/mg) in its crude form has been used in the kinetic resolution of enzyme-catalyzed reaction of 1,2-O-isopropylidene-sn-glycerol and vinyl acetate as acyl donor in the organic solvent n-hexane. It was observed that the enantioselectivity is in the range of 2.295 to 2.235 while ΔΔGD,L -73.408 to -75.682 kJ/mol at 35 °C and 55 °C, respectively . This shows that any increase in the reaction temperature led to an increased final conversion, but it has no effect on the enantioselectivity of the reaction. Also, the thermodynamic effect of temperature on the Gibbs free energy in the lipase-catalyzed kinetic resolution of the reaction between racemic isopropylidene glycerol and vinyl acetate remains in the small range. By using this type of analysis, the researchers may predict if they should increase or decrease the temperature to enhance the selectivity of enzyme in catalyzing a reaction.

Keywords

Enantioselectivity, Lipase, Kinetic resolution

Supporting Institution

Institute fur Technische Chemie Universitat Hannover

Thanks

Thanks to Prof. Dr. Thomas Scheper for giving the opportunities and possibilities to recover this research.

References

• 1. Yun Y, Gellman AJ. Enantioselective Separation on Naturally Chiral Metal Surfaces: d,l -Aspartic Acid on Cu(3,1,17) R & S Surfaces. Angew Chem Int Ed. 2013 Mar 18;52(12):3394–7.
• 2. Fujii N, Saito T. Homochirality and life. Chem Rec. 2004;4(5):267–78.
• 3. Blackmond DG. The origin of biological homochirality. Philos Trans R Soc B Biol Sci. 2011 Oct 27;366(1580):2878–84.
• 4. Sallembien Q, Bouteiller L, Crassous J, Raynal M. Possible chemical and physical scenarios towards biological homochirality. Chem Soc Rev. 2022;51(9):3436–76.
• 5. Armstrong DW, Chang CD, Li WY. Relevance of enantiomeric separations in food and beverage analyses. J Agric Food Chem. 1990 Aug;38(8):1674–7.
• 6. Nguyen LA, He H, Pham-Huy C. Chiral drugs: an overview. Int J Biomed Sci IJBS. 2006 Jun;2(2):85–100.
• 7. Bachmanov AA, Bosak NP, Glendinning JI, Inoue M, Li X, Manita S, et al. Genetics of Amino Acid Taste and Appetite. Adv Nutr Int Rev J. 2016 Jul;7(4):806S-822S.
• 8. Wu Q, Lv H, Zhao L. Applications of carbon nano materials in chiral separation. Trends Anal Chem. 2020;129:115941.
• 9. Mwamwitwa KW, Kaibere RM, Fimbo AM, Sabitii W, Ntinginya NE, Mmbaga BT, et al. A retrospective cross-sectional study to determine chirality status of registered medicines in Tanzania. Sci Rep. 2020 Dec;10(1):17834.
• 10. Kumar R. Effects of Stereoisomers on Drug Activity. Am J Biomed Sci Res. 2021 Jun 21;13(3):220–2.
• 11. Hancu G, Modroiu A. Chiral Switch: Between Therapeutical Benefit and Marketing Strategy. Pharmaceuticals. 2022 Feb 17;15(2):240.
• 12. Peepliwal A, Bagade S, Bonde C. A review: stereochemical consideration and eudismic ratio in chiral drug development. J Biomed Sci Res. 2010;2(1):29–45.
• 13. Genva M, Kenne Kemene T, Deleu M, Lins L, Fauconnier ML. Is It Possible to Predict the Odor of a Molecule on the Basis of its Structure? Int J Mol Sci. 2019 Jun 20;20(12):3018.
• 14. Bodák B, Breveglieri F, Mazzotti M. On the model-based design and comparison of crystallization-based deracemization techniques. Chem Eng Sci. 2022 Jun;254:117595.
• 15. Gogoi A, Mazumder N, Konwer S, Ranawat H, Chen NT, Zhuo GY. Enantiomeric Recognition and Separation by Chiral Nanoparticles. Molecules. 2019 Mar 13;24(6):1007.
• 16. Anderson NG. Developing Processes for Crystallization-Induced Asymmetric Transformation. Org Process Res Dev. 2005 Nov 1;9(6):800–13.
• 17. Robl S, Gou L, Gere A, Sordo M, Lorenz H, Mayer A, et al. Chiral separation by combining pertraction and preferential crystallization. Chem Eng Process Process Intensif. 2013 May;67:80–8.
• 18. Xie R, Chu LY, Deng JG. Membranes and membrane processes for chiral resolution. Chem Soc Rev. 2008;37(6):1243.
• 19. Liu T, Li Z, Wang J, Chen J, Guan M, Qiu H. Solid membranes for chiral separation: A review. Chem Eng J. 2021 Apr;410:128247.
• 20. Han H, Liu W, Xiao Y, Ma X, Wang Y. Advances of enantioselective solid membranes. New J Chem. 2021;45(15):6586–99.
• 21. Ong CS, Oor JZ, Tan SJ, Chew JW. Enantiomeric Separation of Racemic Mixtures Using Chiral-Selective and Organic-Solvent-Resistant Thin-Film Composite Membranes. ACS Appl Mater Interfaces. 2022 Mar 2;14(8):10875–85.
• 22. Tong S. Liquid-liquid chromatography in enantioseparations. J Chromatogr A. 2020 Aug;1626:461345.
• 23. Fanali S, Chankvetadze B. Some thoughts about enantioseparations in capillary electrophoresis. ELECTROPHORESIS. 2019 May 21;elps.201900144.
• 24. Bernardo-Bermejo S, Sánchez-López E, Castro-Puyana M, Marina ML. Chiral capillary electrophoresis. TrAC Trends Anal Chem. 2020 Mar;124:115807.
• 25. Ward TJ, Ward KD. Chiral Separations: A Review of Current Topics and Trends. Anal Chem. 2012 Jan 17;84(2):626–35.
• 26. Ahmed M, Kelly T, Ghanem A. Applications of enzymatic and non-enzymatic methods to access enantiomerically pure compounds using kinetic resolution and racemisation. Tetrahedron. 2012;68(34):6781–802.
• 27. Qayed WS, Aboraia AS, Abdel-Rahman HM, Youssef AF. Lipases-catalyzed enantioselective kinetic resolution of alcohols. J Chem Pharm Res. 2015;7(5):311–22.
• 28. Verho O, Bäckvall JE. Chemoenzymatic Dynamic Kinetic Resolution: A Powerful Tool for the Preparation of Enantiomerically Pure Alcohols and Amines. J Am Chem Soc. 2015 Apr 1;137(12):3996–4009.
• 29. Hall M. Enzymatic strategies for asymmetric synthesis. RSC Chem Biol. 2021;2(4):958–89.
• 30. Mu R, Wang Z, Wamsley MC, Duke CN, Lii PH, Epley SE, et al. Application of Enzymes in Regioselective and Stereoselective Organic Reactions. Catalysts. 2020 Jul 24;10(8):832.
• 31. Bering L, Thompson J, Micklefield J. New reaction pathways by integrating chemo- and biocatalysis. Trends Chem. 2022 May;4(5):392–408.
• 32. Burek BO, Dawood AW, Hollmann F, Liese A, Holtmann D. Process Intensification as Game Changer in Enzyme Catalysis. Front Catal. 2022;2:1–18.
• 33. Wang F, Liu Y, Du C, Gao R. Current Strategies for Real-Time Enzyme Activation. Biomolecules. 2022 Apr 19;12(5):599.
• 34. Sikora A, Siódmiak T, Marszałł MP. Kinetic Resolution of Profens by EnantioselectiveEsterification Catalyzed by Candida antarctica and Candida rugosa Lipases: KINETIC RESOLUTION OF ANTI-INFLAMMATORY DRUGS. Chirality. 2014 Oct;26(10):663–9.
• 35. Kovács B, Forró E, Fülöp F. Candida antarctica lipase B catalysed kinetic resolution of 1,2,3,4-tetrahydro-ß-carbolines: Substrate specificity. Tetrahedron. 2018 Nov;74(48):6873–7.
• 36. Reetz MT. Lipases as practical biocatalysts. Curr Opin Chem Biol. 2002 Apr;6(2):145–50.
• 37. Bornscheuer UT, Bessler C, Srinivas R, Hari Krishna S. Optimizing lipases and related enzymes for efficient application. Trends Biotechnol. 2002 Oct;20(10):433–7.
• 38. Houde A, Kademi A, Leblanc D. Lipases and Their Industrial Applications: An Overview. Appl Biochem Biotechnol. 2004;118(1–3):155–70.
• 39. Bornscheuer UT, Ordoñez GR, Hidalgo A, Gollin A, Lyon J, Hitchman TS, et al. Selectivity of lipases and esterases towards phenol esters. J Mol Catal B Enzym. 2005 Nov;36(1–6):8–13.
• 40. Knežević Z, Šiler-Marinković S, Mojović L. Immobilized Lipases as Practical Catalysts. APTEFF. 2004;35:151–64.
• 41. Mojović L, Šiler-Marinković S, Kukić G, Vunjak-Novaković G. Rhizopus arrhizus lipase-catalyzed interesterification of the midfraction of palm oil to a cocoa butter equivalent fat. Enzyme Microb Technol. 1993 May;15(5):438–43.
• 42. Knezevic ZD, Siler-Marinkovic SS, Mojovic LV. Kinetics of lipase-catalyzed hydrolysis of palm oil in lecithin/izooctane reversed micelles. Appl Microbiol Biotechnol. 1998 Mar 27;49(3):267–71.
• 43. Lortie R. Enzyme catalyzed esterification. Biotechnol Adv. 1997 Jan;15(1):1–15.
• 44. Rathi P, Saxena RK, Gupta R. A novel alkaline lipase from Burkholderia cepacia for detergent formulation. Process Biochem. 2001 Oct;37(2):187–92.
• 45. Zaks A, Dodds DR. Application of biocatalysis and biotransformations to the synthesis of pharmaceuticals. Drug Discov Today. 1997 Dec;2(12):513–31.
• 46. Rasor JP, Voss E. Enzyme-catalyzed processes in pharmaceutical industry. Appl Catal Gen. 2001 Nov;221(1–2):145–58.
• 47. Zuegg J, Hönig H, Schrag JD, Cygler M. Selectivity of lipases: Conformational analysis of suggested intermediates in ester hydrolysis of chiral primary and secondary alcohols. J Mol Catal B Enzym. 1997 Jun;3(1–4):83–98.
• 48. Miyazawa T, Kurita S, Shimaoka M, Ueji S, Yamada T. Resolution of racemic carboxylic acids via the lipase-catalyzed irreversible transesterification of vinyl esters. Chirality. 1999;11(7):554–60.
• 49. Miyazawa T, Imagawa K, Yanagihara R, Yamada T. Marked dependence on temperature of enantioselectivity in the Aspergillus oryzaeprotease-catalyzed hydrolysis of amino acid esters. Biotechnol Tech. 1997;11(12):931–3.
• 50. Sandoval G, Marty A. Screening methods for synthetic activity of lipases. Enzyme Microb Technol. 2007 Feb;40(3):390–3.
• 51. Berglund P. Controlling lipase enantioselectivity for organic synthesis. Biomol Eng. 2001 Aug;18(1):13–22.
• 52. Miyazawa T, Yukawa T, Ueji S, Yanagihara R, Yamada T. Resolution of 2-phenoxy-1-propanols by Pseudomonas sp. lipase-catalyzed highly enantioselective transesterification: influence of reaction conditions on the enantioselectivity toward primary alcohols. Biotechnol Lett. 1998;20(3):235–8.
• 53. Andrade MAC, Andrade FAC, S.Phillips R. Temperature and DMSO increase the enantioselectivity of hydrolysis of methyl alkyl dimethylmalonates catalyzed by pig liver esterase. Bioorg Med Chem Lett. 1991 Jan;1(7):373–6.
• 54. Holmberg E, Hult K. Temperature as an enantioselective parameter in enzymatic resolutions of racemic mixtures. Biotechnol Lett. 1991 May;13(5):323–6.
• 55. Yasufuku Y, Ueji S ichi. Effect of temperature on lipase-catalyzed esterification in organic solvent. Biotechnol Lett [Internet]. 1995 Dec [cited 2022 Apr 2];17(12). Available from: http://link.springer.com/10.1007/BF00189216
• 56. Phillips RS. Temperature modulation of the stereochemistry of enzymatic catalysis: Prospects for exploitation. Trends Biotechnol. 1996 Jan;14(1):13–6.
• 57. Bornscheuer U, Schapöhler S, Scheper T, Schügerl K. Influences of reaction conditions on the enantioselective transesterification using Pseudomonas cepacia lipase. Tetrahedron Asymmetry. 1991 Jan;2(10):1011–4.
• 58. Parmar VS, Prasad AK, Singh PK, Gupta S. Lipase-catalysed transesterifications using 2,2,2-trifluoroethyl butyrate: Effect of temperature on rate of reaction and enantioselectivity. Tetrahedron Asymmetry. 1992 Nov;3(11):1395–8.
• 59. Pham VT, Phillips RS. Effects of substrate structure and temperature on the stereospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus. J Am Chem Soc. 1990 Apr;112(9):3629–32.
• 60. Eyring H. The Activated Complex in Chemical Reactions. J Chem Phys. 1935 Feb;3(2):107–15.
• 61. Straathof AJJ, Jongejan JA. The enantiomeric ratio: origin, determination and prediction. Enzyme Microb Technol. 1997 Dec;21(8):559–71.
• 62. Aydemir A. Modeling of Enzyme Catalyzed Racemic Reactions and Modifications of Enantioselectivity [Internet] [PhD Thesis]. [Hannover, Germany]: Gottfired Leibniz Universitat Hannover; 2010. Available from: https://www.repo.uni-hannover.de/bitstream/handle/123456789/7400/638070449.pdf?sequence=1
• 63. Orrenius C, Hbffner F, Rotticci D, öhrner N, Norin T, Hult K. Chiral Recognition Of Alcohol Enantiomers In Acyl Transfer Reactions Catalysed By Candida Antarctica Lipase B. Biocatal Biotransformation. 1998 Jan;16(1):1–15.
• 64. Sih CJ, Chen CS. Microbial Asymmetric Catalysis?Enantioselective Reduction of Ketones [New Synthetic Methods (45)]. Angew Chem Int Ed Engl. 1984 Aug;23(8):570–8.
• 65. Pham VT, Phillips RS, Ljungdahl LG. Temperature-dependent enantiospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus. J Am Chem Soc. 1989 Mar;111(5):1935–6.
• 66. PHILLIPS RS. Temperature effects on stereochemistry of enzymatic reactions. Enzyme Microb Technol. 1992;14:417–9.
• 67. Monterde MI, Brieva R, Sánchez VM, Bayod M, Gotor V. Enzymatic resolution of the chiral inductor 2-methoxy-2-phenylethanol. Tetrahedron Asymmetry. 2002 Jun;13(10):1091–6.
• 68. Lokotsch W, Fritsche K, Syldatk C. Resolution of d,l-menthol by interesterification with triacetin using the free and immobilized lipase of Candida cylindracea. Appl Microbiol Biotechnol. 1989 Oct;31–31(5–6):467–72.
• 69. Overbeeke PLA, Ottosson J, Hult K, Jongejan JA, Duine JA. The Temperature Dependence of Enzymatic Kinetic Resolutions Reveals the Relative Contribution of Enthalpy and Entropy to Enzymatic Enantioselectivity. Biocatal Biotransformation. 1998 Jan;17(1):61–79.
• 70. Ottosson J, Fransson L, Hult K. Substrate entropy in enzyme enantioselectivity: An experimental and molecular modeling study of a lipase. Protein Sci. 2002 Jun;11(6):1462–71.
• 71. Ema T. Rational strategies for highly enantioselective lipase-catalyzed kinetic resolutions of very bulky chiral compounds: substrate design and high-temperature biocatalysis. Tetrahedron Asymmetry. 2004 Sep;15(18):2765–70.
• 72. Miyazawa T, Kurita S, Ueji S, Yamada T, Kuwata S. Resolution of mandelic acids by lipase-catalysed transesterifications in organic media: inversion of enantioselectivity mediated by the acyl donor. J Chem Soc Perkin 1. 1992;(18):2253.
• 73. Ema T, Maeno S, Takaya Y, Sakai T, Utaka M. Significant effect of acyl groups on enantioselectivity in lipase-catalyzed transesterifications. Tetrahedron Asymmetry. 1996 Mar;7(3):625–8.
• 74. Lin C, Hiraga Y, Masaki K, Iefuji H, Ohkata K. Temperature-dependence of enantioselectivity and desymmetrization in the acetylation of 2-mono- and 2,2-di-substituted 1,3-propanediols by a novel lipase isolated from the yeast Cryptococcus spp. S-2. Biocatal Biotransformation. 2006 Jan;24(5):390–5.
• 75. Ottosson J. Enthalpy and entropy in enzme catalysis, a study of lipase enantioselectivity [PhD Thesis]. [Department of Biotechnology, Stockholm, Sweden]: Royal Institute of Technology; 2001.
• 76. Yasufuku Y, Ueji S. Improvement (5-fold) of enantioselectivity for lipase-catalyzed esterification of a bulky substrate at 57�c in organic solvent. Biotechnol Tech. 1996 Aug;10(8):625–8.
• 77. Yasufuku Y, Ueji S ichi. High Temperature-Induced High Enantioselectivity of Lipase for Esterifications of 2-Phenoxypropionic Acids in Organic Solvent. Bioorganic Chem. 1997 Apr;25(2):88–99.
• 78. Ema T, Yamaguchi K, Wakasa Y, Yabe A, Okada R, Fukumoto M, et al. Transition-state models are useful for versatile biocatalysts: kinetics and thermodynamics of enantioselective acylations of secondary alcohols catalyzed by lipase and subtilisin. J Mol Catal B Enzym. 2003 Jun;22(3–4):181–92.
• 79. SAKAI T. Enhancement of the enantioselectivity in lipase-catalyzed kinetic resolutions of 3-phenyl-2H-azirine-2-methanol by lowering the temperature to -40℃. J Org Chem. 1997;62:4906–7.
• 80. Sakai T, Kishimoto T, Tanaka Y, Ema T, Utaka M. Low-temperature method for enhancement of enantioselectivity in the lipase-catalyzed kinetic resolutions of solketal and some chiral alcohols. Tetrahedron Lett. 1998 Oct;39(43):7881–4.
• 81. Yang H, Jönsson Å, Wehtje E, Adlercreutz P, Mattiasson B. The enantiomeric purity of alcohols formed by enzymatic reduction of ketones can be improved by optimisation of the temperature and by using a high co-substrate concentration. Biochim Biophys Acta BBA - Gen Subj. 1997 Jul;1336(1):51–8.
• 82. Sakai T. ‘Low-temperature method’ for a dramatic improvement in enantioselectivity in lipase-catalyzed reactions. Tetrahedron Asymmetry. 2004 Sep;15(18):2749–56.
• 83. Majumder A, Shah S, Gupta M. Enantioselective transacetylation of (R, S)-beta-citronellol by propanol rinsed immobilized Rhizomucor miehei lipase. Chem Cent J. 2007;1:10.
• 84. Boutelje J, Hjalmarsson M, Hult K, Lindbäck M, Norin T. Control of the stereoselectivity of pig liver esterase by different reaction conditions in the hydrolysis of cis-N-benzyl-2,5-bismethoxycarbonylpyrrolidine and structurally related diesters. Bioorganic Chem. 1988 Dec;16(4):364–75.
• 85. Barton MJ, Hamman JP, Fichter KC, Calton GJ. Enzymatic resolution of (R,S)-2-(4-hydroxyphenoxy) propionic acid. Enzyme Microb Technol. 1990 Aug;12(8):577–83.
• 86. Cipiciani A, Bellezza F, Fringuelli F, Silvestrini MG. Influence of pH and temperature on the enantioselectivity of propan-2-ol-treated Candida rugosa lipase in the kinetic resolution of (±)-4-acetoxy-[2,2]-paracyclophane. Tetrahedron Asymmetry. 2001 Sep;12(16):2277–81.
• 87. Jurczak J, Pikul S, Bauer T. Tetrahedron report number 195 (R)- and (S)-2,3-0-isopropylideneglyceraldehyde in stereoselective organic synthesis. Tetrahedron. 1986 Jan;42(2):447–88.
• 88. Schwarz KH, Kleiner K, Ludwig R, Schrötter E, Schick H. Synthesis of methyl (±)-2,3-O-isopropylideneglycerate by electrochemical oxidation of (±)-1,2-O-isopropylideneglycerol. Liebigs Ann Chem. 1991 May 16;1991(5):503–4.
• 89. Lemaire M, Jeminet G, Gourcy JG, Dauphin G. 2- and 8- functionalized 1,4,7,10-tetraoxaspiro[5.5]undecanes. Tetrahedron Asymmetry. 1993 Jan;4(9):2101–8.
• 90. García M. Synthesis of new ether glycerophospholipids structurally related to modulator. Tetrahedron. 1991;47(48):10023–34.
• 91. Dröge MJ, Bos R, Woerdenbag HJ, Quax WJ. Chiral gas chromatography for the determination of 1,2-O-isopropylidene-sn-glycerol stereoisomers. J Sep Sci. 2003 Jul 1;26(9–10):771–6.
• 92. Lundh M, Nordin O, Hedenström E, Högberg HE. Enzyme catalysed irreversible transesterifications with vinyl acetate. Are they really irreversible? Tetrahedron Asymmetry. 1995 Sep;6(9):2237–44.
• 93. Secundo F, Ottolina G, Riva S, Carrea G. The enantioselectivity of lipase PS in chlorinated solvents increases as a function of substrate conversion. Tetrahedron Asymmetry. 1997 Jul;8(13):2167–73.
• 94. Zanoni G, Agnelli F, Meriggi A, Vidari G. Enantioselective syntheses of isoprostane and iridoid lactones intermediates by enzymatic transesterification. Tetrahedron Asymmetry. 2001 Jul;12(12):1779–84.
• 95. Bornscheuer U, Stamatis H, Xenakis A, Yamane T, Kolisis FN. A comparison of different strategies for lipase-catalyzed synthesis of partial glycerides. Biotechnol Lett. 1994 Jul;16(7):697–702.
• 96. Tservistas M. Untersuchungen zum Einsatz von überkritischem Kohlendioxid als Medium für biokatalysierte Reaktionen [Dissertation]. [Hannover, Germany]: Leibniz Univesitat Hannover; 1997.
• 97. Capewell A, Wendel V, Bornscheuer U, Meyer HH, Scheper T. Lipase-catalyzed kinetic resolution of 3-hydroxy esters in organic solvents and supercritical carbon dioxide. Enzyme Microb Technol. 1996 Aug;19(3):181–6.
• 98. Yildirim A. Lipase Catalysed Transesterification of Isopropyledene Glycerol [Master of Science Thesis]. [Hannover, Germany]: Gottfired Leibniz Universitat Hannover; 2005.
• 99. Chen CS, Sih CJ. General Aspects and Optimization of Enantioselective Biocatalysis in Organic Solvents: The Use of Lipases[New Synthetic Methods(76)]. Angew Chem Int Ed Engl. 1989 Jun;28(6):695–707.
• 100. Rakels JLL, Straathof AJJ, Heijnen JJ. A simple method to determine the enantiomeric ratio in enantioselective biocatalysis. Enzyme Microb Technol. 1993 Dec;15(12):1051–6.
• 101. Persson M, Costes D, Wehtje E, Adlercreutz P. Effects of solvent, water activity and temperature on lipase and hydroxynitrile lyase enantioselectivity. Enzyme Microb Technol. 2002 Jun;30(7):916–23.