Boc-phenylalanine Grafted Poly(3,4-propylenedioxythiophene) Film for Electrochemically Chiral Recognition of 3,4- Dihydroxyphenylalanine Enantiomers Niu Jun-Long, Chai Ke-Ke, Zeng Mei-Xing, Wang Tian-Tian, Zhang Chun-Yan, Chen Shuai, Xu Jing-Kun, Duan Xue-Min Cite this article as: Niu Jun-Long, Chai Ke-Ke, Zeng Mei-Xing, Wang Tian-Tian, Zhang Chun-Yan, Chen Shuai, Xu Jing-Kun, Duan Xue-Min. Boc- phenylalanine Grafted Poly(3,4-propylenedioxythiophene) Film for Electrochemically Chiral Recognition of 3,4- Dihydroxyphenylalanine Enantiomers[J]. Chinese J. Polym. Sci, 2019, 37(5): 451-461. doi: 10.1007/s10118-019-2211-6 View online: https://doi.org/10.1007/s10118-019-2211-6 Articles you may be interested in Synthesis and Characterization of D-/L-methionine Grafted PEDOTs for Selective Recognition of 3,4-Dihydroxyphenylalanine Enantiomers Chinese J. Polym. 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Sci. 2019, 37, 451–461 Boc-phenylalanine Grafted Poly(3,4-propylenedioxythiophene) Film for Electrochemically Chiral Recognition of 3,4-Dihydroxyphenylalanine Enantiomers Jun-Long Niua, Ke-Ke Chaia, Mei-Xing Zenga, Tian-Tian Wanga, Chun-Yan Zhanga, Shuai Chena*, Jing-Kun Xua,b*, and Xue-Min Duana* a Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China b School of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, China Abstract To prepare chiral monomer with single chiral center and higher stereospecificity, a pair of amino-functionalized chiral 3,4- propylenedioxythiophene (ProDOT) derivatives, chiral (3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl) amino]-3-phenylpropanoate (ProDOT-Boc-Phe), were synthesized. Chiral poly[(3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate] (PProDOT-Boc-Phe) modified electrodes were synthesized via potentiostatic polymerization of chiral ProDOT-Boc-Phe. Chiral PProDOT-Boc-Phe films displayed good reversible redox activities. The enantio- selective recognition between chiral PProDOT-Boc-Phe modified glassy carbon electrodes and DOPA enantiomers was achieved by different electrochemical technologies, including cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV). (D)-PProDOT-Boc-Phe and (L)-PProDOT-Boc-Phe showed higher peak current responses toward L-DOPA and D- DOPA, respectively. Keywords Chiral conducting polymer; Amino acids; Chiral sensors; 3,4-Dihydroxyphenylalanine; Electrochemistry Citation: Niu, J. L.; Chai, K. K.; Zeng, M. X.; Wang, T. T.; Zhang, C. Y.; Chen, S.; Xu, J. K.; Duan, X. M. Boc-phenylalanine grafted poly(3,4- propylenedioxythiophene) film for electrochemically chiral recognition of 3,4-dihydroxyphenylalanine enantiomers. Chinese J. Polym. Sci. 2019, 37, 451–461. INTRODUCTION Spectroscopy methods mainly include nuclear magnetic res- onance (NMR)[8] and circular dichroism spectroscopy In human body, most biological molecules have chiral struc- (CD).[6] Chromatography methods mainly include high per- ture and show extreme stereospecificity to chiral drug enantio- [7] [1] formance liquid chromatography (HPLC), gas chromato- mers. Chiral drugs usually have at least one pair of optical graphy (GC),[9] and capillary electrophoresis (CE).[10] The enantiomers. In many instances, only one enantiomer of spectroscopy and chromatography methods have higher effi- these chiral drugs is biochemically active, while the other ciency and accuracy. However, they need to be equipped enantiomer is inactive or even toxic.[2] For example, L-dihy- with expensive instruments, and the operation is time-con- droxyphenylalanine (L-DOPA) has an evident treatment ef- suming and with much complexity. Compared with the fect for Parkinson’s disease. However, D-dihydroxyphenyl- methods mentioned above, electrochemical chiral sensors alanine (D-DOPA) has no treatment effect on Parkinson’s have lower cost, higher sensitivity, and can be operated and disease. D-DOPA will accumulate in human body and give maintained easily, thus attracting more and more atten- an unnecessary burden to patients.[3,4] Therefore, it is nece- tion.[11,12] Chiral electrode materials with unique properties ssary to develop a convenient method for differentiating en- are very important to the chiral electrochemical sensors. antiomers. With unique π orbital structure, conducting polymers are Classically, a number of techniques have been used for sensitive to the alterations of chain conformation.[13] When chiral recognition, which can be split into three categories: the chain conformation of conducting polymers is perturbed, spectroscopy, chromatography, and sensor methods.[5−7] chiral conducting polymers can convert the perturbations to fast and sensitive electrical signals.[14] Moreover, the thick- * Corresponding authors: E-mail [email protected] (S.C.) E-mail [email protected] (J.K.X.) ness of the deposited conducting polymers layer can be con- E-mail [email protected] (X.M.D.) trolled. Thus, conducting polymers have been considered as Received October 15, 2018; Accepted December 11, 2018; Published online promising electrode materials for chiral electrochemical January 14, 2019 sensors.[15] With outstanding stability, high conductivity, and © Chinese Chemical Society Institute of Chemistry, Chinese Academy of Sciences www.cjps.org Springer-Verlag GmbH Germany, part of Springer Nature 2019 link.springer.com 452 Niu, J. L. et al. / Chinese J. Polym. Sci. 2019, 37, 451–461 excellent adhesive properties, 3,4-ethylenedioxythiophene acids have ordered structure, better biocompatibility, and (EDOT) is considered as an ideal electrode material for elec- lower toxicity.[27] Furthermore, most amino acids are chiral, trode surface modification.[16] Given that PEDOT does not and have higher stereospecificity. Therefore, amino acids are show chiral properties, some chiral substituents are required ideal chiral functional groups to be introduced into the Pro- to be introduced into the polymer side chain. DOT-based conducting polymer. By attaching chiral functional groups to the backbone of In this work, chiral Boc-phenylalanine, as the chiral func- PEDOT, many chiral PEDOT derivatives have been synthes- tional group, was introduced into ProDOT by covalent bond- ized. Based on the transetherification of 3,4-dialkoxythio- ing. A pair of chiral ProDOT derivatives, namely chiral (3,4- phenes and chiral 1,2-diols, Caras-Quintero and Bäuerle re- dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-((tert- ported a variety of chiral disubstituted PEDOT derivati- butoxycarbonyl)amino)-3-phenylpropanoate (ProDOT-Boc- ves.[17] Akagi et al. prepared a pair of copolymer-type chiral Phe) were synthesized for the first time. Then, the polymers PEDOT derivatives, which were made up of EDOT and chir- were electrosynthesized in dichloromethane (DCM). Further, al phenylene as spacer.[18] In our previous study, a series of the circular dichroism, spectroscopic properties, morpho- EDOT-based chiral conducting polymers were synthesized logy, and electrochemical behavior of the chiral PProDOT- by grafting chiral hydroxymethyl,[19] chloromethyl,[20] Boc-Phe films were investigated. Finally, sensors based on phenylpropionic acid,[21] methionine,[22] leucine,[23] and chiral PProDOT-Boc-Phe were used to recognize DOPA en- phenylalanine.[24] The chemical structures of the chiral antiomers. EDOT derivatives are illustrated in Scheme 1. However, when natural chiral molecules, namely amino acids, are in- EXPERIMENTAL troduced into the PEDOT chains, PEDOT derivatives have an extra chiral center in the ethylene bridge groups. It is dif- Materials ficult to obtain pure chiral enantiomers when monomer has (3,4-Dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methanol an extra chiral center. In addition, the extra chiral center is (ProDTM) and N-(tert-butoxycarbonyl)-D-/L-phenylalanine (Boc-D-/L-Phe) were prepared according to the synthesis detrimental to the formation of ordered structures, and could [24,28] affect the stereoselective interactions between chiral electro- route described in our previous work. N,N′-dicyclo- chemical sensors and enantiomers. In order to resolve this hexyl-carbodiimide (DCC, 99%) was purchased from Tianjin problem, we have introduced hydroxymethyl[19] and chloro- Damao Chemical Reagent Factory (Tianjin, China). 4- methyl[20] groups