Novel membrane materials having EEE derivatives as a chiral recognition site

doi:10.1016/S0014-3057(00)00121-X

European Polymer Journal

Volume 37, Issue 2, February 2001, Pages 335-342

https://doi.org/10.1016/S0014-3057(00)00121-X Get rights and content

Abstract

Molecularly imprinted polymeric membranes with tripeptide residue H–Glu(OBzl)–Glu(OBzl)–Glu(OBzl)–CH₂– (EEE) were prepared during the membrane preparation process in the presence of a print molecule. The Boc–l-Trp imprinted polymeric membranes thus obtained showed adsorption selectivity toward the print molecule analogue, Ac–l-Trp. From the adsorption isotherms of Ac–Trp’s, the chiral recognition site, which was formed by the print molecule in the membrane preparation process, exclusively recognizes Ac–l-Trp, and the opposite isomer, Ac–d-Trp, is rejected. Enantioselective electrodialysis was attained and the separation factor toward l-isomer reached 5.0, reflecting adsorption selectivity. The membrane performance, such as the amount of enantiomer recognized and flux value of enantioselective electrodialysis, are greatly dependent on the concentration of tripeptide residues in the membrane.

Introduction

These days, optically pure enantiomers have been in demand more and more in the pharmaceutical industry, and for agricultural chemicals, food production, perfumes, specialty materials, and so on. Optical resolution is now carried out by applying the following techniques, such as preferential crystallization, chemical modification to a diastereomer with an optical resolution agent, and high-performance liquid chromatography (HPLC). These conventional optical resolution techniques, excepting simulated moving bed, belonging to the category of HPLC and requiring complicated operation, are batch processes. If optical resolution is realized by using membranes, a large amount of racemic mixtures are expected to be continuously treated. To this end, some membranologists have been investigating the development of optical resolution membranes [1]. The authors’ research group is one of them, who have been studying chiral separation with synthetic polymeric membranes since 1994 [2]. Tetrapeptide derivatives were prepared as candidate materials for optical resolution and they were converted to chiral recognition sites by applying alternative molecular imprinting technique. Recently, it was made clear that the tripeptide derivative, H–Glu(OBzl)–Phe–Phe–CH₂– (EFF), was also converted to a chiral recognition site as tetrapeptide derivatives [3]. It is interesting and important to improve the membrane performance of optical resolution. The concentration of chiral recognition site in the membrane is one of the important factors to regulate optical resolution ability. To this end, in the present article, a tripeptide derivative of H–Glu(OBzl)–Glu(OBzl)–Glu(OBzl)–CH₂– (EEE) were newly prepared, and the effect of chiral recognition site concentration on optical resolution was investigated.

Section snippets

Materials

Protected amino acid, Boc–l-Glu(OBzl), was kindly provided by Kyowa Hakko Kogyo Co., Ltd. Chloromethylated polystyrene resin (Cl-resin) (1% divinylbenzene), in which Cl content was 0.78 meq g⁻¹, and dicyclohexylcarbodiimide (DCC) were purchased from Peptide Institute, Inc., Osaka, Japan, and used without further purification. Dichloromethane [4], trifluoroacetic acid (TFA) [4], diisopropylethylamine (DIEA) [5], and 2-propanol [4] were purified by the usual methods. The copolymer from

Adsorption selectivity of racemic amino acids

Fig. 1 shows the effect of EEE-derivative concentration on adsorption selectivity. In this case, the molecular imprinting conditions, $[Boc – l -Trp]/[EEE]$ , was fixed to be 0.5 and the EEE concentration of the membrane was changed from 0.091 to 0.28 mol dm⁻³. In the present paper, the amount of amino acids adsorbed in the membrane are given as relative ones, which were converted to a EEE derivative basis for convenience in the following discussion. The membranes studied in this paper gave l-isomer

Conclusions

Molecularly imprinted polymeric membranes with tripeptide residue were prepared during the membrane preparation process in the presence of a print molecule. The Boc–l-Trp imprinted polymeric membranes thus obtained showed adsorption selectivity toward the print molecule analogue, Ac–l-Trp, for which absolute configuration is the same as that of print molecule. From the adsorption isotherms of Ac–Trp’s, the chiral recognition site, which was formed by the print molecule in the membrane

Acknowledgements

Support from the Ministry of Education, Science, Sports, and Culture (Monbusho) (Grant-in-Aid for Scientific Research on Priority Areas, No. 706: Dynamic Control of Stereochemistry) is gratefully acknowledged. We wish to thank Prof. Dr. Takeo Shimidzu of Kansai Research Institute, Professor Emeritus of Kyoto University, for his continuous encouragement.

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Novel membrane materials having EEE derivatives as a chiral recognition site

Abstract

Introduction

Section snippets

Materials

Adsorption selectivity of racemic amino acids

Conclusions

Acknowledgements

Anal Biochem

React Func Polym

Macromol Chem Phys

J Am Chem Soc

Angew Chem Int Ed Engl