Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

Abstract

Abstract: The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol·L^-1 phosphate buffer, pH 8) at 37℃ for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the catalytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (K_cat/K_m) was enhanced to 151.91 L·mmol^-1·min^-1, twice as large as that for the buffer solution only.

Key words: catalytic antibody, ibuprofen, enantioselective hydrolysis, water-miscible organic-solvent, conversion

摘要： The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol·L^-1 phosphate buffer, pH 8) at 37℃ for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the catalytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (K_cat/K_m) was enhanced to 151.91 L·mmol^-1·min^-1, twice as large as that for the buffer solution only.

关键词: catalytic antibody, ibuprofen, enantioselective hydrolysis, water-miscible organic-solvent, conversion

YANG Gensheng, YING Li, OU Zhimin, YAO Shanjing. Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents[J]. , 2009, 17(3): 506-512.

杨根生, 应黎, 欧志敏, 姚善泾. Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents[J]. , 2009, 17(3): 506-512.

References

1 Mayer, J.M., Testa, B., “Pharmacodynamics, pharmacokinetics and toxicity of ibuprofen enantiomers”, Drugs Fut., 22, 1347-1366(1997).
2 Adams, S.S., Bresloff, P., Mason, C.G., “Pharmacological differences between the optical isomers of ibuprofen:Evidence for metabolic inversion of the R-(-)-isomer”, J. Pharm. Pharmacol., 28, 256-257(1976).
3 Geisslinger, G., Schuster, O., Stock, K.P., Loew, D., Bach, G.L., Brune, K., “Pharmacokinetics of S-(+)and R-(-)-ibuprofen in volunteers and first clinical experience with S-(+)-ibuprofen in rheumatoid arthritis”, Eur. J. Clin. Pharmacol., 38, 493-497(1990).
4 Mills, R.F., Adams, S.S., Cliffe, E.E., Dickinson, W., Nicholson, J.S., “The metabolism of ibuprofen”, Xenobiotica, 3, 589-598(1973).
5 Caldwell, J., Hutt, A.J., Gigleux-Fournel, S., “The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences”, Biochem. Pharmacol., 37, 105-114(1988).
6 Williams, K., Day, R., Knihinicki, R., Duffield, A., “The stereoselective uptake of ibuprofen enantiomers into adipose tissue”, Biochem. Pharmacol., 35, 3403-3405(1986).
7 Sheldon, R.A., Chirotechnology, Industrial Synthesis of Optically Active Compounds, Marcell Dekker, New York(1993).
8 Kumar, I., Manju, K., Jolly, R.S., “A new biocatalyst for the preparation of enantiomerically pure 2-arylpropanoic acids”, Tetrahedron:Asymmetry, 12, 1431-1434(2001).
9 Long, W.S., Kamaruddin, A.H., Bhatia, S., “Enzyme kinetics of kinetic resolution of racemic ibuprofen ester using enzymatic membrane reactor”, Chem. Eng. Sci., 60, 4957-4970(2005).
10 Naik, P.U., Nara, S.J., Harjani, J.R., Salunkhe, M.M., “Ionic liquid anchored substrate for enzyme catalysed kinetic resolution”, J. Mol. Catal. B:Enzym., 44, 93-98(2007).
11 Wang, Y.J., Hu, Y., Xu, J., Luo, G.S., Dai, Y.Y., “Immobilization of lipase with a special microstructure in composite hydrophilic CA/hydrophobic PTFE membrane for the chiral separation of racemic ibuprofen”, J. Membr. Sci., 293, 133-141(2007).
12 Tramontano, A., Janda, K.D., Lerner, R.A., “Catalytic antibodies”, Science, 234, 1566-1570(1986).
13 Pollack, S.J., Jacobs, J.W., Schultz, P.G., “Selective chemical catalysis by an antibody”, Science, 234, 1570-1573(1986).
14 Tanaka, F., “Catalytic antibodies as designer proteases and esterases”, Chem. Rev., 102, 4885-4906(2002).
15 Jovic, F., Louise, L., Mioskowski, C., Renard, P.Y., “Immunologically driven antibodies chemical engineering:Design and synthesis of a hapten aimed at nerve agent hydrolysis”, Tetrahedron Lett., 46, 6809-6814(2005).
16 Reymond, J.L., Reber, J.L., Lerner, R.A., “Enantioselective, multigram-scale synthesis with a catalytic antibody”, Angew. Chem. Int. Ed. Engl., 33, 475-477(1994).
17 Durfor, C.N., Bolin, R.J., Sugasawara, R.J., Jacobs, J.W., Schultz, P.G., “Antibody catalysis in reverse micelles”, J. Am. Chem. Soc., 110, 8713-8714(1988).
18 Franqueville, E., Loutrari, H., Mellou, F., Stamatis, H., Friboulet, A., Kolisis, F.N., “Reverse micelles, a system for antibody-catalysed reactions”, J. Mol. Catal. B:Enzym., 21, 15-17(2003).
19 Turner, J.M., Bui, T., Lerner, R.A., Barbas, C.F., List, B., “An efficient benchtop system for multigram-scale kinetic resolutions using aldolase antibodies”, Chem. Eur. J., 6, 2772-2774(2000).
20 Harlow, E., Lane, D., Antibodies, A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York(1988).
21 Bradford, M.M., “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding”, Anal. Biochem., 72, 248-254(1976).
22 Guo, H.Y., Tang, L.H., Su, M., Xue, J.P., Xu, X.P., “Screening of a lipase with high enantioselectivity and its application in the resolution of racemic ibuprofen”, The Chinese Journal of Process Engineering, 7, 1169-1174(2007).
23 Chen, C.S., Fujimoto, Y., Girdaukas, G., Sih, C.J., “Quantitative analyses of biochemical kinetic resolutions of enantiomers”, J. Am. Chem. Soc., 104, 7294-7299(1982).
24 Lee, W.H., Kim, K.J., Kim, M.G., Lee, S.B., “Enzymatic resolution of racemic ibuprofen esters:Effects of organic cosolvents and temperature”, J. Fermen. Bioeng., 80, 613-615(1995).

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