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Electrochemical Enantioselective Recognition in a Highly Ordered Self-Assembly Framework Yongxin Tao, Xiaogang Gu, Baozhu Yang, Linhong Deng, Liping Bao, Yong Kong, Fuqiang Chu, and Yong Qin Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.6b04377 • Publication Date (Web): 06 Jan 2017 Downloaded from http://pubs.acs.org on January 9, 2017

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Analytical Chemistry

Electrochemical Enantioselective Recognition in a Highly Ordered Self-Assembly Framework

Yongxin Tao, Xiaogang Gu, Baozhu Yang, Linhong Deng, Liping Bao, Yong Kong,* Fuqiang Chu, and Yong Qin Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Changzhou University, Changzhou 213164, China

Email: [email protected] Tel.: 86-519-86330256; fax: 86-519-86330167.

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ABSTRACT: Construction of convenient systems for isomer discrimination is of great importance for medical and life sciences. Here, we report a simple and effective chiral sensing device based on a highly ordered self-assembly framework. Cu2+-modified β-cyclodextrin (Cu--CD) was self-assembled to the ammonia-ethanol co-treated chitosan (ae-CS), and the highly ordered framework was gradually formed during the “re-growth” process of the shrinked ae-CS films. Tryptophan (Trp) isomers were well discriminated with the highly ordered framework by electrochemical approach. This study is the first example showing how an ordered structure influences chiral recognition.


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INTRODUCTION Chiral discrimination remains of fundamental significance for understanding of the living world, since the amazingly chiral-selective body exhibits different physiological responses to the isomers of a chiral molecule.1 Among the bioactive chiral substances, amino acids are molecular building blocks of life, and efficient discrimination of amino acids isomers with convenient systems is of great importance for biochemistry, pharmaceutics, and medical sciences.2,3 Although several strategies have been proposed during the past decades,4-6 the design of structurally simple yet efficient devices for chiral recognition still remains as an urgent task. Recently, electrochemical chiral recognition with polysaccharides as the chiral recognition elements has drawn enormous attention due to their simplicity and extensive sources.7-12 While it is a promising chiral recognition paradigm, the easy aggregation of polysaccharides caused by intermolecular force decreases the recognition efficiency and limits its practical applications. Here, we report a highly ordered self-assembly framework composed of Cu2+-modified β-cyclodextrin

(Cu--CD)

and

ammonia-ethanol

co-treated

chitosan

(ae-CS)

for

electrochemical chiral recognition of tryptophan (Trp) isomers. Chitosan (CS) underwent a significant shrinkage after the co-treatment with ammonia-ethanol solution, and then the integration of Cu--CD with the shrinked ae-CS led to “re-growth” of the ae-CS films and thus creation of a highly ordered self-assembly framework, which was proven to be an efficient chiral sensing platform for the analysis of Trp isomers. Electrochemical chiral discrimination with this novel highly ordered self-assembly framework (ae-CS/Cu--CD) is present in the following. 3 ACS Paragon Plus Environment


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EXPERIMENTAL SECTION Reagents and Apparatus. L-Tryptophan (L-Trp, 99%), D-tryptophan (D-Trp, 98%), L-tyrosine (L-Tyr, 99%), D-tyrosine (D-Tyr, 98%), L-phenylalanine (L-Phe, 99%) and D-phenylalanine (D-Phe, 99%) were purchased from Aladdin Chemistry Co., Ltd. (Shanghai,

China). β-Cyclodextrin (β-CD) was received from Zibo Qianhui Biological Technology Co., Ltd. (Zibo, China). CS, copper sulfate pentahydrate (CuSO45H2O) and other chemicals not mentioned were purchased from Sinopharm Chemical Reagent Shanghai Co., Ltd. (SCRC, China). All solutions were prepared with ultrapure water (18.2 MΩ). The FT-IR spectra of ae-CS, Cu--CD and ae-CS/Cu--CD self-assembly were recorded by a Nicolet FTIR-8400S spectrophotometer (Shimadzu, Japan). The molecular dynamics (MD) simulation was accomplished by Gaussian09 software package. The surface topographies of the self-assembly framework were characterized by a JPK NanoWizard3 atomic force microscope (AFM, Germany) and a Supra55 field emission scanning electron microscope (FESEM, Germany), respectively. The zeta potentials of CS and ae-CS were determined by a ZEN3600 zeta potential analyzer (Malvern, England). Contact angles were measured using a DSA25 contact angle goniometer (Kruss GmbH, Germany). In each measurement, a 2 μL droplet of water was dispensed onto the tested substrates. Electrochemical experiments were carried out in a conventional three-electrode cell connected to a CHI-660D electrochemical workstation. The working electrode was a glassy carbon electrode (GCE, 3 mm in diameter) modified with the ae-CS/Cu--CD self-assembly framework, the counter electrode was a platinum foil (10  5 mm), and the reference electrode was a saturated calomel electrode (SCE). The temperatures adopted for the 4 ACS Paragon Plus Environment

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preparation of the self-assembly framework and the incorporation of Trp isomers into the ae-CS/Cu--CD framework were precisely controlled by an intelligent thermostatic bath (Ningbo Scientz Biotechnology Co., Ltd. China) Preparation of ae-CS Modified GCE. A total of 50 mg CS was dissolved in 25 mL of 0.1 M HCl, and then a three-electrode system with a polished GCE as the working electrode was transferred into the solution of the protonated CS (2 mg mL-1). Next, a constant potential of –0.5 V (vs. SCE) was applied at the GCE for 375 s for the electrodeposition of the positively charged CS onto the surface of GCE. Finally, the CS modified GCE (CS/GCE) was immersed into a ammonia-ethanol solution (containing 2.5 wt% ammonia) for 15 min, and the obtained ae-CS modified GCE (ae-CS/GCE) was dried in ambient air.. Preparation of ae-CS/Cu-β-CD Self-Assembly Modified GCE. Cu-β-CD was synthesized according to the previous reports.13,14 Briefly, a total of 15 mL 0.04 M CuSO4 aqueous solution was added to 10 mL of 0.5 M NaOH containing 0.02 M β-CD, and blue precipitates of Cu(OH)2 were formed immediately. After continuous stirring for 12 h at room temperature, the mixture was filtered to remove the Cu(OH)2 precipitates, and then 200 mL of ethanol was added to the filtrate for the precipitation of Cu-β-CD. After a standing for 24 h and the subsequent filtration, blue solids of Cu-β-CD were obtained. The as-synthesized Cu-β-CD was thoroughly washed with ethanol and ultrapure water, respectively, and then it was dried at 25 °C in a vacuum drying oven. The ae-CS/GCE mentioned above was placed into 5 mM Cu-β-CD dissolved in 25 mL of 0.1 M phosphate buffer saline (PBS, pH 7.0), and then the self-assembly of Cu-β-CD to the ae-CS was accomplished at different temperatures for a certain time. Figure 1 is the 5 ACS Paragon Plus Environment


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schematic illustration showing the preparation of the ae-CS/Cu-β-CD self-assembly modified GCE (ae-CS/Cu-β-CD/GCE).

Figure 1. Schematic illustration showing the preparation of ae-CS/Cu-β-CD self-assembly modified GCE.

Chiral Discrimination of Trp Isomers with ae-CS/Cu-β-CD/GCE. The as-prepared ae-CS/Cu-β-CD/GCE was immersed into 25 mL of 0.8 mM L- or D-Trp aqueous solution of different pH values (3.0 ~ 9.0) for 30 s, and then chiral discrimination of Trp isomers was assessed

by

recording

the

differential

pulse

voltammograms

(DPVs)

of

the

ae-CS/Cu-β-CD/GCE incorporated with L- or D-Trp at a scan rate of 100 mV s-1 and calculating the peak current ratio of L-Trp to D-Trp (IL-Trp/ID-Trp, an indicator of recognition efficiency). To investigate the temperature-sensitive recognition with the ordered self-assembly framework, temperature was precisely controlled from 5 to 40 °C for the incorporation of Trp isomers to the ae-CS/Cu-β-CD. Each DPV measurement was repeated in triplicate and the standard deviation was calculated for labeling the error bars. After each DPV measurement, the ae-CS/Cu-β-CD/GCE was regenerated by cyclic voltammetry (CV) in 0.1 M PBS of pH 7.0 for twenty consecutive scanning cycles between 0.4 and 1.2 V at a scan rate of 100 mV s-1 to restore the activity of the self-assembly framework. RESULTS AND DISCUSSION


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Formation of the Highly Ordered ae-CS/Cu--CD Self-Assembly. Figure 2 shows the FESEM images of different systems modified on GCE. CS electrodeposited on GCE displays a loose honeycomb structure (Figure 2A). Owing to the dehydration effect of ethanol, the CS films are greatly shrinked after the co-treatment with ammonia-ethanol solution (Figure 2B). Amazingly, the incorporation of Cu--CD to the shrinked CS results in a highly ordered self-assembly framework, as shown in Figures 2C and 2D. On one hand, Cu2+ modified at the wider opening of the hydrophobic cavity of -CD is capable of forming coordinate bonds with the free amine groups (–NH2) on CS;15 on the other hand, Cu--CD molecules are bridge-connected each other by H-bonds formed via the primary hydroxyl groups (–OH) on -CD rims. The synergistic effects of coordinate bonds and H-bonds contribute to the “re-growth” of the shrinked ae-CS films, forming the highly ordered self-assembly framework. The shrinkage of the CS films and the “re-growth” of the shrinked ae-CS films can also be proven by the AFM characterization (Figure S1). It should be emphasized that ammonia also plays a crucial role in the formation of the highly ordered self-assembly framework. The –NH2 on CS is protonated (zeta potential, +63.6 mV) since CS is dissolved in 0.1 M HCl solution, and the electrostatic repulsion between the Cu2+ on Cu--CD and CS makes Cu--CD difficult to be self-assembled. The positively charged –NH3+ on CS can be neutralized to –NH2 (zeta potential, +0.7 mV) with ammonia, which is favorable for the coordinate bonds between Cu2+ and ae-CS. To obtain theoretical informations regarding the structures of the self-assembly, the density functional theory (DFT)16 at M062X functional17,18 is adopted to optimize the structures of the ground state without symmetry constrains. The 6-311+G(d) basis sets are employed 7 ACS Paragon Plus Environment


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for C, N, O, H, and Cu atoms, and the optimized structures of the ae-CS/Cu--CD self-assembly are shown in Figure 3. The interatomic distance of Cu–N is calculated to be 2.26 Å, less than that in a rigorous C3-symmetric coordination environment (2.355 Å),19 suggesting the formation of stable coordinate bonds between Cu2+ and ae-CS.

Figure 2. FESEM images of CS/GCE (A), ae-CS/GCE (B) and ae-CS/Cu--CD/GCE (C and D).

Figure 3. Optimized structures of ae-CS/Cu--CD by DFT.

Characterization

of

the

ae-CS/Cu-β-CD

Self-Assembly.

The

as-prepared

ae-CS/Cu--CD is characterized by FT-IR, CV and electrochemical impedance spectroscopy (EIS) analysis. Figure 4 shows the FT-IR spectra of Cu--CD, ae-CS and ae-CS/Cu--CD over the wavenumber range from 950 to 400 cm-1. For Cu--CD, the peak at 877 cm-1 is attributed to the vibrations of HOH coordinated with Cu2+,20 and another deteriorated peak at 8 ACS Paragon Plus Environment

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580 cm-1 could be ascribed to the vibrations of Cu–O. For ae-CS, the characteristic peak at 890 cm-1 is attributed to the N–H out-of-plane bending vibrations. For the self-assembly framework, a sharp peak is observed at 562 cm-1 owing to the vibrations of the newly formed Cu–N,21 indicating that Cu--CD is successfully incorporated to the ae-CS films via the coordinate bonds between Cu2+ and the free amino groups on the ae-CS. ae-CS/Cu-ß-CD

%Transmittance

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


ae-CS

562 Cu-N

890 N-H Cu-ß-CD 877

580 Cu-O

950 900 850 800 750 700 650 600 550 500 450 400 Wavenumber (cm-1)

Figure 4. FT-IR spectra of Cu-β-CD, ae-CS and ae-CS/Cu-β-CD.

The CVs of different modified electrodes in 0.1 M KCl containing 5 mM Fe(CN)64-/3- are shown in Figure 5A. A pair of well-defined redox peaks due to the conversion between Fe(CN)64- and Fe(CN)63- appears at all the tested systems. Compared with bare GCE, the electrochemical activity and reversibility are enhanced a little at the CS/GCE, suggesting the electrodeposition of CS on the GCE is favorable for the electron transfer at the electrode-solution interfaces. This could be attributed to the strong electrostatic attractions between the protonated –NH2 on CS and Fe(CN)64-/3-. After the treatment with ammonia-ethanol solution, the positive charges on CS are neutralized and the electrochemical activity at the resultant ae-CS/GCE is decreased. Both the electrochemical activity and the electrochemical reversibility are further decreased when Cu--CD is introduced to the electrode, implying the self-assembly of Cu--CD to the ae-CS/GCE. The 9 ACS Paragon Plus Environment


successful construction of the self-assembly framework is also proven by the EIS analysis (Figure 5B). Among the four tested systems, the ae-CS/Cu--CD/GCE exhibits the largest interfacial charge transfer resistance (Rct, 620 Ω), which is higher than those of CS/GCE (33 Ω) and ae-CS/GCE (528 Ω), and it agrees well with the results of CV. 800

(A)

100

b a c

50

d

0 -50

GCE CS/GCE ae-CS/GCE ae-CS/Cu-ß-CD/GCE

-100 -150

-0.2

0.0

0.2

0.4

Z-imaginary (ohm)

150

I (µA)

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(B)

b

CPE

600

Rs Rct

a

Wd

400 c

200 d

0

0.6

0

200

E (V vs. SCE)

400

Z-real (ohm)

600

800

Figure 5. Cyclic voltammograms (A) and Nyquist plots (B) of different systems in 0.1 M KCl solution containing 5 mM Fe(CN)64-/3-. (a) bare GCE, (b) CS/GCE, (c) ae-CS/GCE, (d) ae-CS/Cu-β-CD/GCE. Inset of (B): equivalent circuit, where CPE is the constant phase element, Rs is the solution resistance, Rct is the interfacial charge transfer resistance, and Wd is the Warburg resistance.

Indispensable Role of Cu2+ in the Formation of the ae-CS/Cu-β-CD Self-Assembly. Metal ions can be used to tune assembled nanostructures22 and even trigger chiral nanostructures.23 To obtain further information regarding the role of Cu2+ in the formation of the highly ordered ae-CS/Cu--CD self-assembly framework, the FESEM images of the ae-CS/GCE treated with blank PBS containing neither Cu--CD nor

-CD

(ae-CS/PBS/GCE),

with

PBS

containing

5

mM

Cu--CD

(ae-CS/Cu--CD/GCE) and -CD (ae-CS/-CD/GCE) for 24 h are recorded, as shown in 10 ACS Paragon Plus Environment

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Figure 6. The ae-CS/PBS/GCE exhibits an irregular morphology (Figure 6A), suggesting the random “re-growth” of the ae-CS films in the absence of any inducing substance. Ordered structure is still not observed for the ae-CS/-CD/GCE (Figure 6B) although -CD molecules can be self-assembled to the ae-CS films via H-bonds and there also exist intermolecular H-bonds among the -CD molecules. This behavior can be explained by the fact that the weak H-bonds between -CD and ae-CS could not effectively induce the regular “re-growth” of the ae-CS films in an ordered manner. It is exciting to find that highly ordered self-assembly framework is formed after Cu--CD is self-assembled to the ae-CS films (Figure 6C). Obviously, Cu2+ is indispensable for the growth of the highly ordered framework through the formation of Cu–N coordinate bonds with the free amino groups on the ae-CS. The self-assembled Cu--CD molecules are tightly linked to the ae-CS films via the Cu–N bonds, meanwhile, these Cu--CD molecules are bridge-connected each other through the intermolecular H-bonds, inducing the formation of the highly ordered self-assembly framework during the “re-growth” process of the shrinked as-CS films.



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Figure 6. FESEM images of the ae-CS films treated with blank PBS containing neither Cu--CD nor -CD (A), with PBS containing 5 mM -CD (B) and Cu--CD (C) for 24 h.

Temperature- and Time-dependent Self-Assembly. Schiffrin et al.24 reported that the structure of a supramolecular self-assembly is closely related to the ambient temperature, and thus it is expected that temperature could greatly influence the formation of the self-assembly framework. As shown in Figure 7, the highly ordered micro-framework array grows up gradually with increasing temperature. The partially formed and incomplete ordered architecture at low temperatures (8 and 15 °C) might be attributed to the weak interactions between Cu--CD and ae-CS as well as the unstable H-bonds among the Cu--CD molecules.


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Figure 7. FESEM images of ae-CS/Cu-β-CD/GCE self-assembled at 8 °C (A), 15 °C (B) and 25 °C (C) for 24 h.

In addition, the formation of the highly ordered framework is also found to be dependent on the time for the self-assembly process. When Cu--CD is self-assembled to the ae-CS films for only 6 h, no ordered array is observed (Figure 8A), indicating that insufficient amount of Cu--CD self-assembled in a short period of time can not effectively induce the ordered “re-growth” of the ae-CS films through the formation of enough Cu–N bonds. As the self-assembly time increases to 12 h some ordered structure emerges but the well-ordered architecture is still absent (Figure 8B). As expected, when the time is further prolonged to 18 h and 24 h, the highly ordered self-assembly framework is gradually formed (Figures 8C and 8D), especially at 24 h with the appearance of lots of regular micro-columns. The time-dependency also indicates that Cu--CD plays a crucial role in the formation of the ordered self-assembly, since the amount of Cu--CD assembled to the ae-CS films is determined by the self-assembly time. 13 ACS Paragon Plus Environment


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Figure 8. FESEM images of ae-CS/Cu--CD self-assembled for 6 h (A), 12 h (B), 18 h (C) and 24 h (D) at 25 °C, and the formed self-assemblies are also illustrated.

Electrochemical Enantioselective Recognition in the Self-Assembly Framework. Next, we evaluate the capability of the self-assembly based chiral sensor for recognizing Trp isomers by recording the DPVs of the ae-CS/Cu-β-CD/GCE incorporated with L- and D-Trp (30 °C). We find that the oxidation peak current (Ip) on the DPVs is very different when Land D-Trp are tested respectively (Figure 9A). The Ip ratio (IL-Trp/ID-Trp, an indicator of 14 ACS Paragon Plus Environment

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recognition efficiency) at the self-assembly framework (7.26) is significantly higher than those at individual Cu-β-CD (2.45)9 and sulfonated CS (2.38),8 which could be attributed to the highly ordered structure of the ae-CS/Cu--CD. For better insight into the recognition mechanisms, the influence of self-assembly time on the recognition efficiency (IL-Trp/ID-Trp) is studied. Of particular interest, IL-Trp/ID-Trp increases with increasing self-assembly time, however, the differences in the peak potential (ΔEP) exhibit an opposite tendency (Figure 9B). As previously reported, CS-based electrochemical recognition is accompanied by remarkable ΔEP;8 on the contrary, electrochemical recognition with Cu-β-CD shows little ΔEP on the DPVs.9 Considering the gradually decreased ΔEP with increasing self-assembly time, it might be concluded that either ae-CS or Cu-β-CD plays a dominant role in the chiral recognition at different self-assembly stage since the amount of assembled Cu-β-CD increases gradually with increasing self-assembly time. That is to say, for a relatively short assembly time, the self-assembly framework with less amount of Cu-β-CD exhibits the main chiral characteristics of ae-CS; with increased amount of Cu-β-CD generated from the prolonged assembly time, the chiral recognition gradually turns to be Cu-β-CD controlled. After 24 h of self-assembly, both IL-Trp/ID-Trp and ΔEP vary little, suggesting that the incorporation of Trp isomers to the self-assembly framework reaches a full saturation. To further verify the effectiveness of the highly ordered framework for chiral recognition, Cu-β-CD is directly electrodeposited onto the surface of ae-CS/GCE at –0.5 V instead of self-assembly. The obtained chiral platform is denoted as ae-CS-Cu-β-CD/GCE. Compared to the ae-CS/Cu--CD self-assembly, the DPVs of the ae-CS-Cu-β-CD/GCE incorporated with L- and D-Trp exhibit greatly decreased recognition efficiency (IL-Trp/ID-Trp, 3.01) (Figure 15 ACS Paragon Plus Environment


9C), which could be ascribed to the absence of highly ordered micro-column structure in the ae-CS-Cu-β-CD (Figure 9D). When Cu-β-CD is assembled to ae-CS, the Cu-N coordinate bonds and the intermolecular H-bonds among the Cu-β-CD molecules co-induce the formation of the highly ordered framework during the “re-growth” of the shrinked ae-CS films. For the ae-CS-Cu-β-CD, electrostatic attractions contribute to the formation of the chiral sensor instead of molecular self-assembly, and the absence of the “re-growth” process and the consequent highly ordered framework is unfavorable for the efficient recognition of Trp isomers. Here, it should be emphasized that this study shows, for the first time, how an ordered structure influences chiral recognition. Also, the electrochemical recognition with Cu-β-CD self-assembled to the untreated CS (CS/Cu--CD) is performed for a comparison (Figure S2). The significantly decreased recognition efficiency (IL-Trp/ID-Trp, 1.46) at the CS/Cu--CD/GCE indicates that ae-CS is of great importance for the chiral recognition. 8

(A)

7

5

L-Trp

IL-Trp/ID-Trp

I (µA)

4 3 2 D-Trp

1

80

6 5

60

4 40

3 2

0 0.4

0.5

0.6

0.7

0.8

0.9

1.0

1

20 0

5

10

15

20

25

30

35

40

Self-assembly time (h)

E (V vs. SCE) 4

100

(B)

Delta Ep (mV)

6

(C)

3

I (µA)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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L-Trp

2 D-Trp

1 0.4

0.5

0.6

0.7

0.8

0.9

1.0

E (V vs. SCE)

Figure 9. (A) DPVs of ae-CS/Cu--CD/GCE incorporated with 0.8 mM L- and D-Trp at 30 °C. Self-assembly time, 24 h. (B) Influence of self-assembly time on the recognition efficiency. Error bars


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represent standard deviation for three independent measurements. (C) DPVs of ae-CS-Cu--CD/GCE incorporated with L- and D-Trp at 30 °C. (D) FESEM image of ae-CS-Cu--CD/GCE.

Recognition Mechanisms of the Self-Assembly Framework. Usually, the incorporation of hydrophilic amino acids into a recognition material will enhance its wettability.25 After being immersed into the L-Trp and D-Trp solutions, the ae-CS/Cu--CD self-assembly has different water contact angles: 32.53 ± 1.84o for L-Trp and 25.19 ± 1.66o for D-Trp, respectively (Figure S3), indicating that the self-assembly of ae-CS/Cu--CD has higher affinity for D-Trp than L-Trp. Considering the higher Ip of L-Trp on the DPVs, it is then easy to deduce that the chiral recognition of Trp isomers in the highly ordered self-assembly framework is achieved through the channel-type permeation,26 i.e., the recognition of Trp isomers in the ae-CS/Cu--CD is based on higher permeation of L-Trp through the recognition matrix compared to the opposite isomer. It is also noteworthy that after the assembly of Cu--CD to the ae-CS films, the contact angle is decreased from 45.58 ± 1.21o to 34.74 ± 1.43o, and the enhanced wettability might be attributed to the integration of Cu--CD featured with a hydrophilic outer surface and a hydrophobic central cavity. Temperature-pH Dual Sensitivity Associated with the Self-Assembly. The temperature-pH dual sensitivity associated with the self-assembly framework is further investigated. As previously reported, Trp isomers can be electrochemically discriminated at CS8 and Cu--CD9 modified GCE due to the selectively formed H-bonds between the host (CS or Cu--CD) and the Trp isomers guest, and thus it is expected that temperature might influence the recognition efficiency at the proposed self-assembly of ae-CS/Cu--CD since there is a close relationship between temperature and the strength of H-bonds in the 17 ACS Paragon Plus Environment


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host-guest system. Figure S4 shows the effect of temperature adopted for Trp incorporation on the recognition efficiency. The highest recognition efficiency (IL-Trp/ID-Trp, 7.26) is achieved at 30 °C due to the formation of two stable H-bonds between D-Trp and the high-energy water molecules confined inside the cavity of Cu--CD.9 High-energy water will maintain local molecular correlation and greatly confine its motion at low temperatures;27 meanwhile, the H-bonds network among the CS is also relatively stable at low temperatures,28,29 leading to difficult interactions between ae-CS and Cu--CD for the self-assembly and the decreased recognition efficiency. On the other hand, further increase in temperature would disrupt the H-bonds in the host-guest system as the result of increasing orientational disorder and also deteriorate the recognition efficiency. Figure S5 shows the influence of pH on the recognition capability of the self-assembly. It is evident that IL-Trp/ID-Trp changes remarkably over the tested pH range (3.0 ~ 9.0). The highest recognition efficiency is achieved at pH 6.0 ~ 7.0, which is very close to the isoelectric point of Trp (5.89). Trp is positively charged as pH is less than 5.89; meanwhile, the high-energy water molecules confined in the cavity of Cu--CD are protonated to be H+(H2O)n (n = 6 or 730), and thus the electrostatic repulsion between the protonated water molecules and the positively charged Trp isomers will hinder the incorporation of Trp to the ae-CS/Cu--CD and decrease the recognition efficiency. When pH is further raised from 7.0 to 9.0, Trp turns to be negatively charged and predominantly interacts with the positively charged Cu2+ at the wider opening of the Cu--CD, leading to the aggregation of Trp outside the cavity of the Cu--CD instead of being incorporated into the cavity. The recognition efficiency is, of course, decreased accordingly. Also in this study, the electrodeposition time of CS and the 18 ACS Paragon Plus Environment

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concentration of Trp are optimized to obtain the best performances of the ordered ae-CS/Cu--CD self-assembly (Figures S6 and S7, see the Supporting Information). Chiral Specificity of the Self-Assembly Framework. Finally, the chiral specificity of the proposed ae-CS/Cu--CD is studied using Trp, tyrosine (Tyr) and phenylalanine (Phe) as the model targets. As shown in Figure 10, the recognition efficiency of Trp is greatly higher than those of Tyr and Phe, implying that the highly ordered framework is more suitable for chiral recognition of Trp isomers. The interesting chiral specificity could be attributed to the host-guest size matching principle from the supramolecular point of view.31-33 Generally, -CD host is preferable to the stable inclusion with guest molecules possessing two aromatic rings compared to the mono- and tri-aromatic compounds. Among the three tested amino acids, Trp can be steadily incorporated into the self-assembly host due to the presence of the indole ring (Figure S8), which is consisted of a benzene ring and a five-membered pyrrole ring. 8

6

IL / ID

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4

2

0

Tyr

Phe

Trp

Figure 10. Recognition efficiency of 0.8 mM L, D-phenylalanine (Phe), L, D-tyrosine (Tyr) and L, D-tryptophan (Trp) at the ae-CS/Cu-β-CD/GCE. Error bars represent standard deviation for three

independent measurements. Temperature, 30 oC; pH, 7.0.



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CONCLUSIONS To summarize, we described that the self-assembly of Cu--CD to ae-CS via the formation of Cu-N coordinate bonds and the prior-existing H-bonds among the Cu--CD molecules, inducing the “re-growth” of the shrinked ae-CS films and the formation of a highly ordered framework that is capable of discriminating Trp isomers as well as sensitive to both temperature and pH. In the highly ordered self-assembly, either ae-CS or Cu-β-CD played a dominant role in the chiral discriminating at different self-assembly stage. Of particular interest, such self-assembly chiral interfaces exhibit fascinating selectivity to Trp due to the host-guest size matching principle. This study is the first example showing how an ordered structure influences chiral recognition. On the basis of these findings, we believe that artificial highly ordered framework offer real promise for construction of practical and effective chiral sensing platform that could be employed in fields such as chiral drug discrimination. AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. Notes The authors declare no competing financial interest. ACKNOWLEDGEMENTS This work was supported by Natural Science Foundation of China (21275023, 11532003,21476031), Advanced Catalysis and Green Manufacturing Collaborative Innovation Center (ACGM2016-06-24) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). 20 ACS Paragon Plus Environment

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ASSOCIATED CONTENT Supporting Information Additional figures as noted in the text, the optimization of CS electrodeposition time and Trp concentration. This material is available free of charge via the Internet at http://pubs.acs.org.



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