Postsynthetic Modification Strategy for Constructing Electrochemiluminescence-Active Chiral Covalent Organic Frameworks Performing Efficient Enantioselective Sensing.

Electrochemiluminescence (ECL), integrating the characteristics of electrochemistry and fluorescence, has the advantages of high sensitivity and low background. However, only a few studies have been reported for enantioselective sensing based on the ECL-active platform because of the huge challenges in constructing tunable chiral ECL luminophores. Here, we developed a facile strategy to design and prepare ECL-active chiral covalent organic frameworks (COFs) Ph-triPy+-(R)-Ru(II) for enantioselective sensing. In such an artificial structure, the ionic skeleton of COFs was beneficial to the electron transfer on the working electrode surface and the chiral Ru-ligand was used as the chiral ECL-active luminophore. It was found that Ph-triPy+-(R)-Ru(II) coupled with sodium persulfate (Na2S2O8) as the coreactant exhibited obvious ECL signals. More importantly, a clear difference toward l- and d-enantiomers was observed in the response of the ECL intensity, resulting in a uniform recognition law. That is, for amino alcohols, d-enantiomers (1 mM) measured by Ph-triPy+-(R)-Ru(II) showed a higher ECL intensity compared with l-enantiomers. Differently, amino acids (1 mM) gave an inverse recognition phenomenon. The ECL intensity ratios between l- and d-enantiomers (1 mM) are in the range of 1.25-1.94 for serine, aspartic acid, glutamic acid, valine, leucine, leucinol, and valinol. What is more interesting is that the ECL intensity was closely related to the concentration of l-amino alcohols and d-amino acids, whereas their inverse configurations remained unchanged. In a word, the present concept demonstrates a feasible direction toward chiral ECL-active COFs and their potential for efficient enantioselective sensing.

A Liquid-Liquid Interfacial Strategy for Construction of Electroactive Chiral Covalent-Organic Frameworks with the Aim to Enlarge the Testing Scope of Chiral Electroanalysis.

Although electroactive chiral covalent-organic frameworks (CCOFs) are considered an ideal platform for chiral electroanalysis, they are rarely reported due to the difficult selection of suitable precursors. Here, a facile strategy of liquid-liquid interfacial polymerization was carried out to synthesize the target electroactive CCOFs Ph-Py+-(S,S)-DPEA·PF6- and Ph-Py+-(R,R)-DPEA·PF6-. That is, a trivalent Zincke salt (4,4',4″-(benzene-1,3,5-triyl)tris(1-(2,4-dinitrophenyl)pyridin-1-ium)) trichloride (Ph-Py+-NO2) and enantiopure 1,2-diphenylethylenediamine (DPEA) were dissolved in water and chloroform, respectively. The Zincke reaction occurs at the interface, resulting in uniform porosity. As expected, the cyclic voltammetry and differential pulse voltammetry measurements showed that the tripyridinium units of the CCOFs afforded obvious electrochemical responses. When Ph-Py+-(S,S)-DPEA·PF6- was modified onto the surface of a glassy carbon electrode as a chiral sensor, the molecules, which included tryptophan, aspartic acid, serine, tyrosine, glutamic acid, mandelic acid, and malic acid, were enantioselectively recognized in the response of the peak current. Very importantly, the discriminative electrochemical signals were derived from Ph-Py+-(S,S)-DPEA·PF6-. The best peak current ratios between l- and d-enantiomers were in the range of 1.31-2.68. Besides, a good linear relationship between peak currents and enantiomeric excess (ee) values was established, which was successfully harnessed to determine the ee values for unknown samples. In a word, the current work provides new insight and potential of electroactive CCOFs for enantioselective sensing in a broad range.

π-π+ Interaction Promoting the Absorption of Electroactive Chiral Selectors into the Cavity of Conductive Covalent Organic Framework for Enantioselective Sensing of Electrochemically Silent Molecules.

To date, achieving enantioselective electroanalysis for electrochemically silent chiral molecules is still highly desired. Here, an ionic covalent organic framework (COF) consisting of the pyridinium cation was derived from the tripyridinium Zincke salt and 1,4-phenylenediamine in a one-pot reaction. The electrochemical measurements revealed that the ionic backbone contributed to the electron transfer with a low charge transfer resistance. Besides, the π-π+ interaction between the pyridinium cation and ferrocenyl unit can promote the absorption of electroactive chiral ferrocenyl reagents into the hole of COF, so as to afford the electrochemical signals by themselves, replacing the testing enantiomers. As a result, the electroactive complex used as an electrochemical platform was highly effective at enantiomerically recognizing amino alcohols (prolinol, valinol, leucinol, and alaninol) and amino acids (methionine, serine, and penicillamine), giving the ratios of current intensity between l- and d-enantiomers in the range of 1.46-1.72. Moreover, the density functional theory calculations determined the possible intermolecular interactions between the testing enantiomers and chiral selector: namely, hydrogen bonds and electrostatic attractions. Overall, the present work offers an effective strategy to enlarge the electrochemical scope for chiral recognition based on electroactive chiral COFs.

A chiral metal-organic framework/cyclodextrin sensing interface for the chiral discrimination of tryptophan enantiomers.

A chiral metal-organic framework (CMOF) was synthesized by introducing L-histidine (L-His) to zeolitic imidazolate framework-8 (ZIF-8) and then grafting with carboxymethyl-ß-cyclodextrin (CM-ß-CD). Compared with L-His-ZIF-8, the CM-ß-CD-functionalized L-His-ZIF-8 (L-His-ZIF-8-CD) showed significantly enhanced discrimination ability for the tryptophan (Trp) enantiomers owing to the inherent chirality of CM-ß-CD. The specificity of the chiral interface was also studied, and the results indicated that the discrimination ability for Trp enantiomers is significantly stronger than that for the enantiomers of cysteine (Cys) and tyrosine (Tyr), which might be due to the better matching between the indole ring of Trp and the chiral cavity of CM-ß-CD.

Chiral Metal-Organic Framework with Temperature-Dependent Homochirality for Chiral Discrimination.

Chiral metal-organic frameworks (CMOFs) have attracted considerable attention in chiral discrimination and separation. In this work, a simple CMOF is synthesized through a facile one-pot method by using Zn(II), tetra(4-carboxyphenyl)-porphyrin (TCPP), and d-phenylalanine methyl ester (d-Phe-OMe) as metal ion, organic ligand, and chiral source, respectively. Interestingly, the CMOFs synthesized at different temperatures (25 and 160 °C) display quite different morphologies and diametrically opposite chirality due to the different interaction modes between TCPP and d-Phe-OMe at 25 and 160 °C. Next, the CMOFs synthesized at 25 and 160 °C are utilized for the chiral discrimination of the isomers of tryptophan (Trp), resulting in exactly the reverse effect. The developed CMOF-based chiral sensors also exhibit excellent reproducibility, suggesting their great potential for chiral analysis.

Recent advances of optically active helical polymers as adsorbents and chiral stationary phases for chiral resolution.

Chiral resolution is very important and still a big challenge due to different biological activity and same physicochemical property of one pair (R)- and (S)-isomer. There is no doubt that chiral selectors are essentially needed for chiral resolution, which can stereoselectively interact with a pair of isomers. To date, a large amount of optically active helical polymers as chiral selectors have been synthesized via two strategies. First, the target helical polymers are derived from natural polysaccharide such as cellulose and amylose. Second, they can be synthesized by polymerization of chiral monomers. Alternatively, an achiral polymer is prepared first followed by static or dynamic chiral induction. Furthermore, a part of them is harnessed as chiral stationary phases for chromatographic chiral separation and as chiral adsorbents for enantioselective adsorption/crystallization, resulting in good enantioseparation efficiency. In summary, the present review will focus on recent progress of the polymers with optical activity for chiral resolution, especially the literature published in the past 10 years. In addition, development prospects and future challenges of optically active helical polymers will be discussed in detail.

TiO2 Nanotubes Decorated with CdSe Quantum Dots: A Bifunctional Electrochemiluminescent Platform for Chiral Discrimination and Chiral Sensing.

Chiral analysis is of significant importance for living organisms since chirality is the fundamental phenomenon in nature. In this work, a bifunctional electrochemiluminescent (ECL) platform is constructed for chiral discrimination and chiral sensing. 3-Mercaptopropionic acid-functionalized CdSe quantum dots (CdSe QDs) are combined with aminated TiO2 nanotubes (NH2-TiNTs) via amidation. The resultant CdSe QDs/TiNTs display significantly enhanced ECL signals due to the synergistic effect between CdSe QDs and TiNTs, which are then used for the chiral discrimination of the isomers of nine chiral amino acids (AAs) in the presence of d-AA oxidase (DAAO). DAAO can selectively catalyze the oxidation of d-AAs to generate H2O2, which acts as the coreaction reagent and triggers the ECL signals of CdSe QDs/TiNTs, and thus, the isomers of the nine chiral AAs can be effectively discriminated. In addition, the as-constructed ECL platform can also be used for the sensitive detection of d-AAs in the presence of DAAO with a wide linear range and a low limit of detection. These findings suggest that the CdSe QDs/TiNTs can work as a bifunctional ECL platform (chiral discrimination and chiral sensing), which might be an advanced ECL platform for biomedical applications.

Competitive Self-Assembly Interaction between Ferrocenyl Units and Amino Acids for Entry into the Cavity of ß-Cyclodextrin for Chiral Electroanalysis.

At present, chiral electroanalysis of nonelectroactive chiral compounds still remains a challenge because they cannot provide an electrochemical signal by themselves. Here, a strategy based on a competitive self-assembly interaction of a ferrocene (Fc) unit and the testing isomers entering into the cavity of ß-cyclodextrin (ß-CD) was carried out for chiral electroanalysis. First of all, the Fc derivative was directly bridged to silica microspheres, followed by inclusion into the cavity of ß-CD. As expected, once it was modified onto the surface of a carbon working electrode as an electrochemical sensor, SiO2@Fc-CD-WE, its differential pulse voltammetry signal would markedly decrease compared with the uncovered Fc. Next, when l- and d-isomers of amino acids that included histidine, threonine, phenylalanine, and glutamic acid were examined using SiO2@Fc-CD-WE, it showed an enantioselective entry of amino acids into the cavity of ß-cyclodextrin instead of Fc, resulting in the release of Fc with signal enhancement. For histidine, glutamic acid, and threonine, l-isomers showed a higher peak current response compared with d-isomers. The peak current ratios between l- and d-isomers were 2.88, 1.21, and 1.40, respectively. At the same time, the opposite phenomenon occurred for phenylalanine with a peak current ratio of 3.19 between d- and l-isomers. In summary, we are assured that the recognition strategy based on the supramolecular interaction can enlarge the detection range of chiral compounds by electrochemical analysis.

Recent advances of the ionic chiral selectors for chiral resolution by chromatography, spectroscopy and electrochemistry.

Ionic chiral selectors have been received much attention in the field of asymmetric catalysis, chiral recognition, and preparative separation. It has been shown that the addition of ionic chiral selectors can enhance the recognition efficiency dramatically due to the presence of multiple intermolecular interactions, including hydrogen bond, π-π interaction, van der Waals force, electrostatic ion-pairing interaction, and ionic-hydrogen bond. In the initial research stage of the ionic chiral selectors, most of work center on the application in chromatographic separation (capillary electrophoresis, high-performance liquid chromatography, and gas chromatography). Differently, more and more attention has been paid on the spectroscopy (nuclear magnetic resonance, fluorescence, ultraviolet and visible absorption spectrum, and circular dichroism spectrum) and electrochemistry in recent years. In this tutorial review as regards the ionic chiral selectors, we discuss in detail the structural features, properties, and their application in chromatography, spectroscopy, and electrochemistry.

A surface protein-imprinted biosensor based on boronate affinity for the detection of anti-human immunoglobulin G.

A surface protein-imprinted biosensor was constructed on a screen-printed carbon electrode (SPCE) for the detection of anti-human immunoglobulin G (anti-IgG). The SPCE was successively decorated with aminated graphene (NH2-G) and gold nanobipyramids (AuNBs) for signal amplification. Then 4-mercaptophenylboric acid (4-MPBA) was covalently anchored to the surface of AuNBs for capturing anti-IgG template through boronate affinity binding. The decorated SPCE was then deposited with an imprinting layer generated by the electropolymerization of pyrrole. After removal of the anti-IgG template by the dissociation of the boronate ester in an acidic solution, three-dimensional (3D) cavities complementary to the anti-IgG template were formed in the imprinting layer of polypyrrole (PPy). The molecularly imprinted polymers (MIP)-based biosensor was used for the detection of anti-IgG, exhibiting a wide linear range from 0.05 to 100 ng mL-1 and a low limit of detection of 0.017 ng mL-1 (S/N = 3). In addition, the MIP-based anti-IgG biosensor also shows high selectivity, reproducibility and stability. Finally, the practicability of the fabricated anti-IgG biosensor was demonstrated by accurate determination of anti-IgG in serum sample.

Strategies to Achieve a Ferrocene-Based Polymer with Reversible Redox Activity for Chiral Electroanalysis of Nonelectroactive Amino Acids.

In the past, various chiral isomers accompanied by electroactive units have been distinguished using electrochemical techniques, which can produce electrochemical signals by themselves. However, it is still difficult to use an electrochemical technique to detect nonelectroactive samples. To address this bottleneck, an electroactive chiral polymer (S,S)-p-CVB-Fc that contains one redox-active ferrocene unit was designed and synthesized in this study. The electroactive polymer can give electrochemical signals as an alternative to the tested chiral samples, regardless of whether the isomers have electroactive units. Then, it was fixed on the surface of a glassy carbon electrode as an electrochemical chiral sensor. When nonelectroactive amino acids including proline, threonine, and alanine were examined by the sensor, clear discrimination in the response of peak current could be observed toward l- and d-isomers at pH 6.5. The peak current ratios (IL/ID) for proline and alanine were 1.47 and 1.48, respectively. In contrast, for threonine, the d-isomer exhibited a higher peak current than the l -isomer with a ratio of 2.59. In summary, the results ensure that the current work can enlarge the testing scope of chiral samples in the field of chiral electroanalysis using an electroactive sensor.

Ultrasensitive Electrochemical Impedance Chiral Discrimination and Sensing of Tryptophan Isomers Based on Core-Shell-Structured Au-Ag Nanoparticles.

Au-Ag nanoparticles (Au-Ag NPs) with a core-shell structure are prepared and used for ultrasensitive electrochemical impedance (EI) discrimination of the isomers of tryptophan (Trp). As revealed by circular dichroism, rotary polarization caused by the Au-Ag NPs is consistent with D-Trp but opposite to L-Trp, and thus, the Au-Ag NPs can selectively combine with D-Trp through preferential interactions. Compared with Au-Ag NPs, the composites of D-Trp and Au-Ag NPs (Au-Ag NPs/D-Trp) display significantly increased charge transfer resistance (Rct); differently, the Rct of Au-Ag NPs/L-Trp remains almost unchanged because the Au-Ag NPs exhibit poor affinity toward L-Trp. Therefore, ultrasensitive EI enantiodiscrimination of the isomers of Trp is realized even at an extremely low concentration of the Trp isomers (0.1 nM). In addition, it is successfully applied in the ultrasensitive determination of D-Trp at a low concentration level (0.1 nM∼10 µM).

Electrochemiluminescent chiral discrimination with chiral Ag2S quantum dots/few-layer carbon nitride nanosheets.

Well-dispersed chiral Ag2S quantum dots (Ag2S QDs) were facilely synthesized by using N-acetyl-L-cysteine (NALC) as the chiral ligand and loaded onto nanosheets of two-dimensional (2D) few-layer carbon nitride (C3N4). The resultant nanocomposite (Ag2S QDs/few-layer C3N4) shows enhanced electrochemiluminescence (ECL) while maintaining the chirality of Ag2S QDs, which can be used for the chiral discrimination of the enantiomers of tyrosine (Tyr). Due to the higher affinity of chiral Ag2S QDs toward L-Tyr than toward its enantiomer, the ECL intensity of Ag2S QDs/few-layer C3N4 is significantly decreased after its incubation with L-Tyr, and thus the Tyr enantiomers can be discriminated. The developed ECL chiral sensor exhibits high stability and reproducibility. The universality of the ECL chiral sensor for the discrimination of other chiral amino acids is also studied, and the results indicate that it can work only in the case of chiral aromatic amino acids.

Silver nanoparticle driven signal amplification for electrochemical chiral discrimination of amino acids.

ß-Cyclodextrin (ß-CD) modified silver nanoparticles (AgNPs), denoted as ß-CD/AgNPs, were prepared by a simple one-pot method. Due to the inherent chirality of ß-CD, the developed ß-CD/AgNPs exhibited higher affinity toward l-tyrosine (l-Tyr) than d-tyrosine (d-Tyr), leading to serious aggregation of AgNPs in the presence of l-Tyr. Consequently, the l-Tyr induced aggregation of AgNPs can result in signal amplification in the differential pulse voltammograms (DPVs) of l-Tyr, which can be applied for the electrochemical chiral discrimination of the Tyr enantiomers. Other chiral amino acids including tryptophan and phenylalanine can also be successfully discriminated with the ß-CD/AgNPs, suggesting high universality of the developed chiral sensor.

Enantioselective recognition of tryptophan isomers with molecularly imprinted overoxidized polypyrrole/poly(p-aminobenzene sulfonic acid) modified electrode.

Poly(p-aminobenzene sulfonic acid) (pABSA) was electrodeposited onto the surface of a glassy carbon electrode (GCE), which was then used for the preconcentration of l-tryptophan (l-Trp) due to the electrostatic and π-π interactions between pABSA and l-Trp. Polypyrrole (PPy) was electrodeposited onto the surface of the l-Trp enriched pABSA, and then the l-Trp templates were removed, resulting in molecularly imprinted PPy/pABSA. To avoid the interference from the oxidation peak of PPy on the following electrochemical chiral recognition of Trp isomers, PPy was overoxidized by cyclic voltammetry (CV). The resultant molecularly imprinted overoxidized PPy (OPPy)/pABSA modified GCE exhibits higher affinity toward l-Trp than d-tryptophan (d-Trp); that is, the oxidation peak current of l-Trp is greatly higher than that of d-Trp at the molecularly imprinted OPPy/pABSA modified GCE.

THz-TDS Reflection Measurement of Coating Thicknesses at Non-Perpendicular Incidence: Experiment and Simulation.

Time-domain spectroscopy (TDS) in the terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data themselves without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

Enantioselective Limiting Transport into a Fixed Cavity via Supramolecular Interaction for the Chiral Electroanalysis of Amino Acids Regardless of Electroactive Units.

Although an increasing number of researchers are developing electroanalytical protocols for the chiral recognition of amino acids, the electroactive units of the tested isomers still need to provide corresponding electrical signals. In this study, a supramolecular system was developed for the chiral electroanalysis of amino acids regardless of electroactive units. As a model system, an enantiopure electroactive molecule Fc-(S,S)-1 that includes a ferrocenyl group was synthesized and acted as a guest. Moreover, hydrophobic cyclobis-(paraquat-p-phenylene) (CBPQT4+-2) was used as the host. In the presence of π-π stacking and the attraction of π-electrons, CBPQT4+-2 can encapsulate Fc-(S,S)-1 into its cavity. Next, a screen-printed electrode was utilized for electrochemical chiral recognition. The host was fixed on the surface of the working electrode, and the guest was used as the electroactive chiral selector to support electron transfer. Once different configurations of amino acids (threonine, histidine, glutamine, and leucine) were mixed with the guest, regardless of whether they contained electroactive units, differences in the cyclic voltammetry results of the probe enantiomers could be observed, namely, in the peak currents or peak potentials. However, glutamine was an exception because the L-isomer had a stronger binding affinity with Fc-(S,S)-1 + Cu(II), which would limit the transport of the complex into the cavity of CBPQT4+-2, thereby resulting in a low peak current. Thus, an inverse phenomenon was observed with glutamine. In summary, we believe that this work can increase the testing scope for the chiral recognition of different kinds of isomers using electrochemical tools.

Enantioselective Recognition of Chiral Tryptophan with Achiral Glycine through the Strategy of Chirality Transfer.

Glycine (Gly), an achiral amino acid, has never been reported for enantioselective recognition owing to the absence of chiral sites. Herein, a facile strategy of chirality transfer is proposed to endow Gly with chirality. Optically active CuO, L-CuO, is first prepared, which can be used for the decoration of Gly through the formation of the Cu(Gly)2 complex. Successful chirality transfer from L-CuO to Gly is confirmed by circular dichroism (CD) spectra. The formation of the Cu(Gly)2 complex is further confirmed by Fourier transform infrared spectra and X-ray photoelectron spectroscopy. Next, the resultant L-CuO-Gly is used for chiral analysis of the isomers of tryptophan (Trp). Because of the higher affinity of L-CuO-Gly toward L-Trp than its isomer, the Trp isomers exhibit significant differences in their oxidation peak currents at the L-CuO-Gly-modified glassy carbon electrode (GCE) (IL-Trp/ID-Trp = 5.24). Finally, the practicability of the developed L-CuO-Gly/GCE is assessed, and the results indicate that it could be a reliable chiral sensor for the quantitative analysis of Trp isomers in nonracemic mixtures.

An ionic-based carbon dot for enantioselective discrimination of nonaromatic amino alcohols.

Here, ionized chiral carbon dots, (S,S)-C-dots-1 (λex = 430 nm, λem = 480 nm), were synthesized via a facile route with relatively high quantum yield (∼24.4%) and used as a fluorescent chiral sensor. One of the advantages of the synthetic process is that it avoids the loss of the chiral center. That is, the chiral bromo compound can directly form an ionic pair with the pyridyl group, which is derived from the amine precursor in the first step. Furthermore, (S,S)-C-dots-1 shows clear discrimination toward different configurations of nonaromatic amino alcohols in the presence of Cu(ii). When the (R)-isomer is added to a solution of (S,S)-C-dots-1 + Cu(ii), it shows much higher fluorescent intensity than the (S)-isomer. The values of IR/IS are 2.9 and 2.3 for 2-aminobutan-1-ol and 2-aminopropan-1-ol, respectively. In summary, we believe that this work can expand the synthetic routes and potential applications of functional carbon dots in the field of enantioselective sensing.

Recent progress of enantioseparation under scale production (2014-2019).

Very different from enantiorecognition at an analytical level, preparative enantioseparation at scale production has to confront many problems. In recent years, various separation techniques have been developed with much progress including high-performance liquid chromatography, liquid-liquid extraction, membrane separation, enantioselective solid-phase absorption, and enantioselective precipitation. Among them, in order to achieve high enantiomerical purity of the enantiomers after separation, two approaches are commonly carried out. One is that continuous separation is necessary when one-step separation cannot have satisfactory efficiency. Another is that most of the research groups focus on the construction of novel chiral environment with much more rigid structures of the selectors. Combined with these two aspects, we mainly introduce current topics, trends, strategies related to enantioseparation under large scale.