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.

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.

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.

Highly Reliable Chiral Discrimination of Tryptophan Enantiomers through Two Different Modes: Electrochemistry and Temperature.

Reliable chiral discrimination of enantiomers with simple devices is of great importance for chiral analysis. Here, a chiral sensing platform is developed for chiral discrimination through two different modes: electrochemistry and temperature. Au nanoparticles (AuNPs) are grown in situ on the nanosheets of MXene by utilizing the strong metal reduction ability of MXene, which can be further used for the anchoring of N-acetyl-l-cysteine (NALC), a commonly used chiral source, through Au-S bonds. Owing to the excellent electrical conductivity and photothermal conversion efficiency of MXene, the resultant MXene-AuNPs-NALC is applied in the construction of a chiral sensing platform for the discrimination of tryptophan (Trp) enantiomers through two different modes: electrochemistry and temperature. Compared with conventional single-mode chiral sensors, the proposed chiral sensing platform can integrate two different indicators (currents and temperature) into one chiral sensor, greatly improving the reliability of chiral discrimination.

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.

A chiral sensing platform based on a multi-substituted ferrocene-cuprous ion complex for the discrimination of electroactive amino acid isomers.

An electrochemical chiral sensing platform based on a multi-substituted ferrocene-cuprous ion (Cu+) complex is constructed for the discrimination of electroactive amino acid (AA) isomers. Due to the opposite configurations of the AA isomers, the developed multi-substituted ferrocene-Cu+ can preferably combine with a right-handed AA (D-AA) isomer to form the ternary complex of multi-substituted ferrocene-Cu+-D-AA through π-π interactions, resulting in higher peak currents of D-AA. Therefore, the isomers of electroactive AA can be successfully discriminated. Among the tested electroactive AA isomers, the chiral sensing platform exhibits higher discrimination capability toward the isomers of tryptophan (Trp) than that of tyrosine (Tyr) and cysteine (Cys), which might be ascribed to the stronger π-π interactions between the benzene ring of the multi-substituted ferrocene and the indole ring of the Trp isomers.

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.

An electrochemical chiral sensor based on competitive host-guest interaction for the discrimination of electroinactive amino acids.

A novel electrochemical chiral sensor has been designed based on the principle of competitive host-guest interaction and utilized for the discrimination of electroinactive proline (Pro) isomers. Electroactive methylene blue (MB) was used as the signal probe, which was combined with multi-walled carbon nanotubes (MWCNTs)-decorated ß-cyclodextrin (ß-CD), via host-guest interaction, where the oxidation peak currents of MB decreased after isomers of Pro were combined with the MWCNTs-ß-CD via a competitive host-guest interaction. Due to the steric configuration of L-Pro matching the cavity of ß-CD, more L-Pro than D-Pro was combined with MWCNTs-ß-CD, resulting in a more pronounced decrease of MB peak currents. Therefore, the isomers of Pro could be discriminated. Besides Pro, the isomers of electroinactive histidine (His) could also be discriminated with the chiral sensor. In addition, the contents of L-Pro in non-racemic mixtures could be detected with the developed chiral sensor.

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.

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.

Enhanced Electrochemiluminescence of Porphyrin-Based Metal-Organic Frameworks Controlled via Coordination Modulation.

Precise control over the composition, morphology, and size of porphyrin-based metal-organic frameworks is challenging, but the extension of these hybrid materials will enable the creation of novel electrochemiluminescence (ECL) emitters. The coordination of various entities is made from Zn2+ ions and meso-tetra(4-carboxyphenyl)porphine (TCPP), modulated by both solvent and bathophenanthrolinedisulfonic acid disodium salt (BPS) as capping agent, resulting in limited crystal growth of Zn-TCPP in DMF/H2O (v/v, 1:1) and the formation of nanoscale TCPP-Zn-BPS. The role of BPS is also evaluated using Zn-TCPP and BPS-Zn-TCPP as controls, prepared in the absence of BPS and different coordinating sequences of ligands, respectively. The newly obtained TCPP-Zn-BPS exhibits a variety of different morphologies, as well as spectral and optoelectronic properties. The ECL behavior of TCPP-Zn-BPS is investigated by using H2O2 as co-reactant. The amplification of ECL is further studied by ECL spectroscopies and cyclic voltammetry, with the corresponding mechanism proposed.

Postsynthesis Ligand Exchange Induced Porphyrin Hybrid Crystalloid Reconstruction for Self-Enhanced Electrochemiluminescence.

In traditional coreactant electrochemiluminescence (ECL), the efficiency of the coreactant catalyzed into an active intermediate is one of the dominant factors restricting the luminous intensity. In this work, Co-2-MI-ZnTCPP is designed as a composite material integrating coreaction accelerator (Co-N) and luminophore. Through the catalytic effect of Co-N structures on hydrogen peroxide, the in situ generation and accumulation of active intermediates are achieved, which will react with porphyrin anion radical, thereby bringing out self-enhanced ECL. By adjusting the scanning potential range, the ECL mechanism is thoroughly studied and the contribution of each potential window to the luminescence is obtained. This work provides inspiration for the design of integrated ECL emitters with a coreaction accelerator and luminophore, providing a new way for the construction of a self-enhanced ECL emitter.

Magnetic zirconium hexacyanoferrate(II) nanoparticle as tracing tag for electrochemical DNA assay.

Novel multifunctional magnetic zirconium hexacyanoferrate nanoparticles (ZrHCF MNPs) were prepared, which consisted of magnetic beads (MBs) inner core and zirconium hexacyanoferrate(II) (ZrHCF) outer shell. As an artificial peroxidase, the ZrHCF MNPs exhibited remarkable electrocatalytic properties in the reduction of H2O2 at 0.2 V vs saturated calomel electrode (SCE). On the basis of the bonding interaction between Zr (IV) of the shell ZrHCF framework and phosphonate groups, the 5'-phosphorylated ssDNA probes with a consecutive stretch of guanines as a spacer could be incorporated in ZrHCF MNPs easily. Thus, DNA-grafted ZrHCF MNPs could be simply obtained by magnetic separation. The prepared nanoelectrocatalyst was further used as signal nanoprobe for the ultrasensitive electrochemical DNA assay. Under optimal conditions, the proposed biosensor presents high sensitivity for detecting target DNA with a linear range from 1.0 fM to 1.0 nM and a low detection limit of 0.43 fM. Moreover, it exhibits good performance with excellent selectivity, high stability, and acceptable fabrication reproducibility.

Colorimetric discrimination and spectroscopic detection of tyrosine enantiomers based on melamine induced aggregation of l-cysteine/Au nanoparticles.

Au nanoparticles (AuNPs) are decorated by l-cysteine (L-Cys), and the resultant chiral L-Cys/AuNPs can be used for colorimetric discrimination and spectroscopic detection of the tyrosine (Tyr) enantiomers. Melamine (Mel) can induce the aggregation of the L-Cys/AuNPs through ligand exchange, leading to a distinct color change from wine red to purple. Owing to the same rotatory direction of L-Cys/AuNPs and L-Tyr, the L-Cys/AuNPs exhibit a significantly higher binding affinity toward L-Tyr than D-Tyr, and thus the Mel induced aggregation of the L-Cys/AuNPs is greatly alleviated by the protection from the L-Tyr protective layer. Therefore, the Tyr enantiomers can be simply discriminated by naked eyes. In addition, the absorbance of the aggregated L-Cys/AuNPs at ∼630 nm increases linearly with decreasing concentrations of L-Tyr ranging from 10 nM to 1 mM due to the weakened protection effect from L-Tyr, and thus spectroscopic detection of L-Tyr can also be accomplished by the developed L-Cys/AuNPs with a limit of detection (LOD) of 5.3 nM.

Chiral Ru-Based Covalent Organic Frameworks as An Electrochemiluminescence-Active Platform for the Enantioselective Sensing of Amino Acids.

Although several studies related with the electrochemiluminescence (ECL) technique have been reported for chiral discrimination, it still has to face some limitations, namely, complex synthetic pathways and a relatively low recognition efficiency. Herein, this study introduces a facile strategy for the synthesis of ECL-active chiral covalent organic frameworks (COFs) employed as a chiral recognition platform. In this artificial structure, ruthenium(II) coordinated with the dipyridyl unit of the COF and enantiopure cyclohexane-1,2-diamine was harnessed as the ECL-active unit, which gave strong ECL emission in the presence of the coreactant reagent (K2S2O8). When the as-prepared COF was used as a chiral ECL-active platform, clear discrimination was observed in the response of the ECL intensity toward l- and d-enantiomers of amino acids, including tryptophan, leucine, methionine, threonine, and histidine. The biggest ratio of the ECL intensity between different configurations was up to 1.75. More importantly, a good linear relationship between the enantiomeric composition and the ECL intensity was established, which was successfully employed to determine the unknown enantiomeric compositions of the real samples. In brief, we believe that the proposed ECL-based chiral platform provides an important reference for the determination of the configuration and enantiomeric compositions.

Visual and electrochemical chiral discrimination of tryptophan isomers with shikimic acid chiral ionic liquids-copper ions complex.

Efficient discrimination of amino acids (AAs) isomers is of significant importance for life science and analytical chemistry. Here, a dual-mode chiral discrimination strategy is proposed for visual and electrochemical chiral discrimination of tryptophan (Trp) isomers. Shikimic acid chiral ionic liquids (SCIL) is coordinated with copper ions (Cu2+), and the obtained SCIL-Cu2+ can form ternary complexes with the Trp isomers. Owing to the inherent chirality of SCIL and the reverse homochirality of L-Trp and D-Trp, the ternary complex of SCIL-Cu-D-Trp has higher stability than SCIL-Cu-L-Trp, as revealed by the calculated stability constants (K) and changes in Gibbs free energy (ΔG). The difference in the stability can be utilized for the chiral discrimination of L-Trp and D-Trp, resulting in discernible differences in colors and the electrochemical signals of the Trp isomers. Besides Trp, the isomers of phenylalanine (Phe) can also be discriminated by the proposed dual-mode chiral discrimination strategy with the SCIL-Cu2+ complex.

A photothermal effect-based chiral sensor for chiral discrimination and sensitive detection.

Chiral analysis with simple devices is of great importance for analytical chemistry. Based on the photothermal (PT) effect, a simple chiral sensor with a portable laser device as the light source and a thermometer as the detection tool was developed for the chiral recognition of tryptophan (Trp) isomers and the sensitive sensing of one isomer (L-Trp). Gold nanorods (GNRs), which have outstanding photo-thermal conversion ability due to their localized surface plasma resonance (LSPR) effect, are used as PT reagents, and biomacromolecules bovine serum albumin (BSA) are used as natural chiral sources, and thus, GNRs@BSA was obtained through Au-S bonds. The resultant GNRs@BSA displays higher affinity toward L-Trp than D-Trp owing to the inherent chirality of BSA. Under the irradiation of near-infrared (NIR) light, the temperature of GNRs@BSA//L-Trp is greatly lower than that of GNRs@BSA//D-Trp due to its greatly decreased thermal conductivity, and thus chiral discrimination of Trp isomers can be achieved. In addition, the developed PT effect-based chiral sensor can be used for sensitive detection of L-Trp, and the linear range and limit of detection (LOD) are 1 µM-10 mM and 0.43 µM, respectively.