Chiral Fluorescent Probes for Determination of Both Concentration and Enantiomeric Composition of Amino Acids

doi:10.6023/cjoc202401022

Chinese Journal of Organic Chemistry ›› 2024, Vol. 44 ›› Issue (6): 1862-1869.DOI: 10.6023/cjoc202401022 Previous Articles Next Articles

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测定氨基酸浓度和对映体组成的手性荧光探针

李非凡^a, 余康^a, 倪传志^b, 朱园园^b^,^*(), 曾婕^c^,^*(), 古双喜^a^,^c^,^*()

a 武汉工程大学化工与制药学院绿色化工过程教育部重点实验室新型反应器与绿色化学工艺湖北省重点实验室武汉 430205
b 武汉工程大学化学与环境工程学院武汉430205
c 武汉工程大学药物研究院武汉 430205

收稿日期:2024-01-16 修回日期:2024-05-08 发布日期:2024-03-28
基金资助:
国家自然科学基金(22074114); 国家自然科学基金(22377097); 国家自然科学基金(21877087); 湖北省自然科学基金(2020CFB623); 湖北省自然科学基金(2021CFB556); 磷资源开发利用教育部工程研究中心(LCX202305); 武汉工程大学研究生教学研究项目(2022JYXM09); 武汉工程大学研究生教学研究项目(2021JYXM07); 武汉工程大学研究生教育创新基金(CX2022450)

Chiral Fluorescent Probes for Determination of Both Concentration and Enantiomeric Composition of Amino Acids

Feifan Li^a, Kang Yu^a, Chuanzhi Ni^b, Yuanyuan Zhu^b,*(), Jie Zeng^c,*(), Shuangxi Gu^a^,^c,*()

a Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, Key Laboratory for Green Chemical Process of Ministry of Education, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan 430205
b School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205
c Pharmaceutical Research Institute, Wuhan Institute of Technology, Wuhan 430205

Received:2024-01-16 Revised:2024-05-08 Published:2024-03-28
Contact: * E-mail: yyzhu531@163.com; jiezeng116964@163.com; shuangxigu@163.com
Supported by:
National Natural Science Foundation of China(22074114); National Natural Science Foundation of China(22377097); National Natural Science Foundation of China(21877087); Natural Science Foundation of Hubei Province(2020CFB623); Natural Science Foundation of Hubei Province(2021CFB556); Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(LCX202305); Wuhan Institute of Technology Graduate Education and Teaching Reform Research Project(2022JYXM09); Wuhan Institute of Technology Graduate Education and Teaching Reform Research Project(2021JYXM07); Graduate Innovative Fund of Wuhan Institute of Technology(CX2022450)

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Abstract

A novel 1,1'-bi-2-naphthol (BINOL)-based fluorescent probe (R)-(E)-2,2'-dihydroxy-3'-((quinolin-7-ylimino)methyl)- [1,1'-binaphthalene]-3-carbaldehyde [(R)-2] and its isomer (R)-(E)-2,2'-dihydroxy-3'-((quinolin-6-ylimino)methyl)-[1,1'- binaphthalene]-3-carbaldehyde [(R)-3] were designed and synthesized. The quinoline imine groups at 3'-position of the probes were involved in the molecular recognition of amino acids through complexation between N atom and Zn(II), which synergically enhanced the enantioselectivity of BINOL-aldehyde to amino acids. The probe molecule exhibited chiral independent fluorescence enhancement for various amino acids at 438 nm, while exhibiting excellent enantioselective fluorescence response at 513 nm. The dependence function of the intensities of the above two emission peaks on arginine concentrations and enantiomeric excess (ee) was studied, and the concentrations and ee values of several arginine samples were measured by the fitted function equation. The interaction mechanism between (R)-2 and D-/L-arginine in the presence of Zn²⁺ was investigated by ¹H NMR and HRMS. The thermodynamic stability of the arginine enantiomer/probe/Zn(II) complexes was calculated by Gaussian 16 program to elucidate the origin of the enantioselectivity. This work affords a platform for the determination of the concentration and enantiomeric composition of 7 amino acids (Glu, Arg, Gln, Ser, Thr, Met, Ala) through a single probe.

Key words: fluorescent probe, chiral recognition, enantioselectivity, enantiomeric excess, amino acid

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Feifan Li, Kang Yu, Chuanzhi Ni, Yuanyuan Zhu, Jie Zeng, Shuangxi Gu. Chiral Fluorescent Probes for Determination of Both Concentration and Enantiomeric Composition of Amino Acids[J]. Chinese Journal of Organic Chemistry, 2024, 44(6): 1862-1869.

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Fig. & Tab. 13

Figure 1. Structures of (S,S)-1[8] and quinoline-containing fluorescent probes L1 and L2 for Zn(II)[9e-9f]

Figure 2. Structures of the designed compounds (R)-2 and (R)-3

Scheme 1. Synthesis of (R)-2

Figure 3. Fluorescence spectra of (a) (R)-2 and (b) (R)-3 [17 μmol/L in dimethyl sulfoxide (DMSO), 1.0 equiv.] with L-Arg (blue line) and D-Arg (cyan line) (in pH 7.4 HEPES buffer, 50.0 equiv.) in the presence of Zn(OAc)2 (in H2O, 4.0 equiv.) (λexc=363 nm, slit=3 nm/3 nm)

Figure 4. Fluorescence spectra of (a) (R)-2 and (b) (R)-3 (17 μmol/L in DMSO, 1.0 equiv.) with L-Arg (blue line) and D-Arg (cyan line) (in pH 7.4 HEPES buffer, 50.0 equiv.) in the presence of Zn(OAc)2 (in H2O, 4.0 equiv.) (λexc=445 nm, slit=5 nm/5 nm)

Figure 5. Structures of the three contrast compounds 6-AQ, 7-AQ and (R)-5

Figure 6. Fluorescence intensity at (a) 438 nm (λexc=363 nm. slit: 3 nm/3 nm) and (b) 513 nm (λexc=445 nm. slit: 5 nm/5 nm) vs the standing time The mixtures contain (R)-2 (17 μmol/L in DMSO, 1.0 equiv.), L-/D-Arg (in pH 7.4 HEPES buffer, 50.0 equiv.) and Zn(OAc)2 (in H2O, 4.0 equiv.).

Figure 7. Fluorescence intensity at 438 nm vs the concentration of L-Arg (black line) and D-Arg (red line) and the fitted linear relationship between the average value of I438nm and concentration of Arg (blue) line The mixtures contain (R)-2 (17 μmol/L in DMSO, 1.0 equiv.), L-/D-Arg (in pH 7.4 HEPES buffer, 0-50.0 equiv.) and Zn(OAc)2 (in H2O, 7.0 equiv.). λexc=363 nm. slit: 3 nm/3 nm, Error bars are from three independent experiments.

Figure 8. Fluorescence intensity at 513 nm versus the ee values of D-Arg The mixtures contain (R)-2 (17 μmol/L in DMSO, 1.0 equiv.), Arg with different ee values (in pH 7.4 HEPES buffer, 40.0 equiv.) and Zn(OAc)2 (in H2O, 7.0 equiv.). λexc=445 nm. Slit: 5 nm/5 nm. Error bars are from three independent experiments.

Sample	ee of sample/%	Actual concentration/(mmol•L^–1)	Determined concentration^a/(mmol•L^–1)	Absolute error/(mmol•L^–1)
1	100	4	5.44	1.44
2	–100	10	9.66	0.34
3	–51	11	13.37	2.37
4	–18	15	15.51	0.51
5	21	19	18.91	0.09
6	49	24	22.65	1.35
7	–100	27	28.08	1.08
8	82	28	26.89	1.11

Table 1. Determination of the concentration of Arg samples by (R)-2 under excitation at 363 nm.

Sample	Actual ee/%	Determined ee^a/%	Absolute error/%
9	–84	–82.45	1.55
10	–69	–68.71	0.29
11	–35	–30.59	4.41
12	18	14.05	3.95
13	77	78.59	1.59

Table 2. Determination of the ee values of Arg samples by (R)-2 under excitation at 445 nm

Figure 9. Fluorescence response at (a) 438 nm (λexc=363 nm, slit=3 nm/3 nm) and (b) 513 nm (λexc=445 nm, slit=5 nm/5 nm) for the mixtures of (R)-2 (17 μmol/L in DMSO, 1.0 equiv.)+Zn(OAc)2 (in H2O, 4.0 equiv.) with 19 pairs of amino acids (in pH 7.4 HEPES buffer, 50 equiv.)

Figure 10. Deduced structures and Gibbs free energy of the complex 8 and 9, which are from the reactions of (R)-2+Zn(II) with D-Arg and L-Arg, respectively

References 9

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测定氨基酸浓度和对映体组成的手性荧光探针

Chiral Fluorescent Probes for Determination of Both Concentration and Enantiomeric Composition of Amino Acids

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