Enantioselective Recognition Research Articles

Enantio- and Substrate-Selective Recognition of Chiral Neurotransmitters with C3-Symmetric Switchable Receptors.

We report on the synthesis of C3-symmetric enantiopure cage molecules 1, which exhibit remarkable to exclusive enantioselective recognition properties toward chiral ammonium neurotransmitters. Strong changes in the substrate selectivity are also observed when different stereoisomers of 1 are used. Furthermore, protonation/deprotonation induces a reversible modification of the conformation of 1, which switches from an imploded to an inflated form, leading to ejection and reuptake of the guest initially encaged inside the cavity.

Recent advances of BINOL-based sensors for enantioselective fluorescence recognition.

Enantioselective fluorescent sensors show large potential for fast, real-time, and highly sensitive measurement of the concentration and enantiomeric composition of chiral molecules. Among all of the sensors, BINOL-based sensors have been actively investigated and extensively used to carry out highly enantioselective, sensitive recognition of chiral α-hydroxycarboxylic acids, amino acids, amino acid derivatives, amino alcohols and amines. In this manuscript, the recent progress of chiral BINOL-based sensors for enantioselective fluorescence recognition of different substrates is reviewed and discussed. The structure of BINOL is tuned by introducing various groups or molecules which systematically changed its fluorescence properties and offered potential for rapid assays of chiral organic molecules. From the development of this area, we gain fresh insight into the challenges and chances of BINOL-based sensors.

A sensitive metal–organic framework nanosensor with cation-introduced chirality for enantioselective recognition and determination of quinine and quinidine in human urine

Additional chiral centers have been introduced into Cd-MOF to prepare a novel luminescent probe (1-C-Eu), which demonstrates promise in the enantioselective recognition and detection of quinine and quinidine in human urine.

The construction of helicate metal–organic nanotubes and enantioselective recognition

Self-assembling metal–organic nanotubes (HMOF-2) acts as an excellent fluorescence sensor for fast, convenient, sensitive and enantioselective recognition of d/l-tartaric acid and d- or l-lactic acid with adverse properties in the food industry.

Chiral conducting polymer nanomaterials: synthesis and applications in enantioselective recognition

Recent progress made in the synthesis, mechanism, and applications involving the enantioselective separation and sensing of chiral conducting polymer nanomaterials has been reviewed.

Chemoselective and enantioselective fluorescent recognition of glutamic and aspartic acids.

A highly chemoselective as well as enantioselective fluorescent probe has been discovered for the recognition of the acidic amino acids, including glutamic acid and aspartic acid. This study has established a novel amino acid recognition mechanism by an aldehyde-based fluorescent probe.

Tuning residual chirality in carbon dots with anti-microbial properties.

Chirality remains a critical consideration in drug development and design, as well as in applications of enantioselective recognition and sensing. However, the preparation of chiral nanomaterials requires extensive post synthetic modifications with a chiral agent, coupled with extensive purification. This limits the use and application of chiral nanomaterials. Herein, we report a facile, one-step microwave-assisted synthesis of chiral carbon dots through the reaction of l- and d-cysteine amino acid precursors and citric acid. We modulated the synthetic parameters to preserve and tune the residual chiral properties of the dots and demonstrate that the reaction conditions play a critical role in dictating the chiral behaviour of the dots. Finally, in a proof of concept application we demonstrated that the synthesized carbon dots, particularly d-carbon dots inhibit bacterial growth at a lower concentration than l-carbon dots. By varying bacterial strains and chirality of the carbon dots, concentrations ranging from 0.25–4 mg mL−1 of the nanoparticles were required to inhibit microbial growth. The ability to preserve and tune chirality during synthesis can open up novel avenues and research directions for the development of enantioselective materials, as well as antibacterial films and surfaces.

Electrospinning chiral fluorescent nanofibers from helical polyacetylene: preparation and enantioselective recognition ability.

Chirality is ubiquitous in nature and closely related to the pharmacological effects of chiral drugs. Therefore, chiral recognition of molecular enantiomers becomes an important research theme. Fluorescence detection is highly sensitive and fast but has achieved only limited success in enantiomeric detection due to the lack of powerful chiral fluorescence detection materials. In this paper, a novel chiral fluorescent probe material, i.e. a chiral fluorescent nanofiber membrane, is prepared from chiral helical substituted polyacetylene by the electrospinning technique. The SEM images demonstrate the success in fabricating continuous, uniform nanofibers with a diameter of about 100 nm. Circular dichroism spectra show that the nanofibers exhibit fascinating optical activity. One of the enantiomeric chiral fluorescent membranes has chiral fluorescence recognition effects towards alanine and chiral phenylethylamine, while the other enantiomeric membrane does not. The prepared chiral fluorescent nano-materials are expected to find various applications in chirality-related fields due to their advantages such as chirality, fluorescence, and a high specific surface area. The established preparation approach also promises a potent and versatile platform for developing advanced nanofiber materials from conjugated polymers.

Gold nanodendrite-based differential potential ratiometric sensing strategy for enantioselective recognition of DOPA

Numerous chiral drugs have been developed for neurological diseases, but chiral drug safety and pharmacological research still faces great challenges in enantioselectivity and sensitivity of chiral analysis. A rapid, stable and high-efficiency gold nanodendrite-based electrochemical sensing method was proposed as a versatile differential potential ratiometric strategy for highly selective chiral recognition of dual 3,4-dihydroxyphenylalanine (DOPA) enantiomers. Using simple electrochemical deposition, the gold nanodendrite (AuND) membrane was steadily modified on the glassy carbon electrode (GCE) with high specific chiral identifiability and robust signal amplifiability. Based on a sequence of systematic optimization, an apparent potential difference (PD) was detected up to 108 mV from oxidation peaks of DOPA enantiomers. Furthermore, according to a regulatable concentration range from 10 μM to 100 μM, different proportions of L-/d-DOPA had a good linear relationship with corresponding peak potentials (Eps) in the racemic mixture. Superior to traditional enantiorecognition of single chiral drug, both DOPA enantiomers enabled to be simultaneously distinguished with high repeatability, selectivity, and anti-interference ability on the AuND/GCE. This unique semi-quantitative AuND-based potential sensing strategy was proposed to efficiently quantify the proportion of L-/d-DOPA for chiral drug recognition, emerging positive potential for numerous applications in pharmacology and clinical diagnosis.

Molecular switch manipulating Prelog priority of an alcohol dehydrogenase toward bulky-bulky ketones

Structure-guided rational design revealed the molecular switch manipulating the Prelog and anti-Prelog priorities of an NADPH-dependent alcohol dehydrogenase toward prochiral ketones with bulky and similar substituents. Synergistic effects of unconserved residues at 214 and 237 in small and large substrate binding pockets were proven to be vital in governing the stereoselectivity. The ee values of E214Y/S237A and E214C/S237 G toward (4-chlorophenyl)-(pyridin-2-yl)-methanone were 99.3% (R) and 78.8% (S) respectively. Substrate specificity analysis revealed that similar patterns were also found with (4’-chlorophenyl)-phenylmethanone, (4’-bromophenyl)-phenylmethanone and (4’-nitrophenyl)-phenylmethanone. This study provides valuable evidence for understanding the molecular mechanism on enantioselective recognition of prochiral ketones by alcohol dehydrogenase.

Silver‐Mediated Growth of Chiral Ag/Au‐Cysteine Hybrid Nanospheres with Giant Chiroptical Response

AbstractThe chiral Ag/Au‐cysteine hybrid nanospheres (HNSs) have been prepared by using cysteine (Cys) as an inductive agent via wet chemistry methods. Unlike the case of the dipole approximation, the circular dichroism spectra can be divided into two components: 1) one region associated with the interband absorption enhanced optical activity of structural arrangement of Cys molecules at 200–320 nm; 2) another region corresponding to a ligand‐to‐metal charge transfer mixed with ligand‐to‐metal‐metal charge transfer excitation due to the synergetic interplay of the electrostatic interaction between Cys side chains and the Au(I)⋅⋅⋅Au(I) aurophilic attraction in the Au(I)‐Cys complexes, located at 350–400 nm. The chiroptical response increases dramatically with increasing the concentration of Au from 0.1 to 1.56 × 10−3 m, and subsequently decreases with further increasing the concentration of Au from 3.12 to 12.5 × 10−3 m, which is similar to the sergeants and soldiers effect of chiral polymer materials. Furthermore, the circinate‐like morphology of the alloyed nanospheres is strongly dependent on the presence of Ag and the chiral bimetal HNSs present excellent enantioselective recognition for amino acids in catalytic electrochemical reactions due to the specific activity and chiral active spots.

A Highly Luminescent Chiral Tetrahedral Eu4L4(L')4 Cage: Chirality Induction, Chirality Memory, and Circularly Polarized Luminescence.

Chiral lanthanide cages with circularly polarized luminescence (CPL) properties have found potential application in enantioselective guest recognition and sensing. However, it still remains a big challenge to develop a simple and robust method for the diastereoselective assembly of homochiral lanthanide cages in view of the large lability of the Ln(III) ions. Herein, we report the first example of the formation of a enantiopure lanthanide tetrahedral cage via a chiral ancillary ligand induction strategy. One such cage, (Eu4L4)(R/S-BINAPO)4, is assembled by four achiral C3-symmeric tris(β-diketones) (4,4',4″-tris(4,4,4-trifluoro-1,3-dioxobutyl)triphenylamine, L) as faces, four Eu(III) ions as vertices and four chiral R-/S-bis(diphenylphosphoryl)-1,1'-binaphthyl (R/S-BINAPO) as ancillary ligands. X-ray crystallography and NMR and CD spectra confirm the formation of a pair of enantiopure chiral topological tetrahedral cages, (Eu4L4)(R-BINAPO)4 and (Eu4L4)(S-BINAPO)4 (ΔΔΔΔ-1 and ΛΛΛΛ-1). As expected, the tetrahedral cages present strong CPL with |glum| values up to 0.20, while they unexpectedly give ultrahigh luminescent quantum yields (QYs) of up to 81%, the highest value reported in chiral Ln(III) complexes. More impressively, the chiral memory effect for a lanthanide-based assembly is observed for the first time. The chirality of the original cage 1 framework is retained after R/S-BINAPO is replaced by the achiral bis[2-(diphenylphosphino)phenyl] ether oxide (DPEPO), and thus another pair of enantiopure Eu(III) tetrahedral cages, ΔΔΔΔ- and ΛΛΛΛ-[(Eu4L4)(DPEPO)4] (ΔΔΔΔ-2 and ΛΛΛΛ-2), have been isolated. Encouragingly, cage 2 also presents an impressive luminescence quantum yield (QY = 68%) and intense CPL (|glum| = 0.11). This study offers a simple and low-cost synthesis strategy for the preparation of lanthanide cages with CPL properties.

Cation-induced chirality in a bifunctional metal-organic framework for quantitative enantioselective recognition

The integration of luminescence and chirality in easy-scalable metal-organic frameworks gives rise to the development of advanced luminescent sensors. To date, the synthesis of chiral metal-organic frameworks is poorly predictable and their chirality primarily originates from components that constitute the frameworks. By contrast, the introduction of chirality into the pores of metal-organic frameworks has not been explored to the best of our knowledge. Here, we demonstrate that chirality can be introduced into an anionic Zn-based metal-organic framework via simple cation exchange, yielding dual luminescent centers comprised of the ligand and Tb3+ ions, accompanied by a chiral center in the pores. This bifunctional material shows enantioselectivity luminescent sensing for a mixture of stereoisomers, demonstrated for Cinchonine and Cinchonidine epimers and amino alcohol enantiomers, from which the quantitative determination of the stereoisomeric excess has been obtained. This study paves a pathway for the design of multifunctional metal-organic framework systems as a useful method for rapid sensing of chiral molecules.

Electroactive NPs and D-amino acids oxidase engineered electrochemical chiral sensor for D-alanine detection

A simple and accurate magnetic electrochemical sensor is developed for the ultrasensitive chiral recognition of D-amino acids (D-AAs). Fe3O4@Au@Ag@CuxO nanoparticles (NPs) (x = 1, 2) are controllable prepared and used as the electrochemical beacons. The controllable integration of plasmonic metal NPs, semiconductors and magnetic NPs enables multilayered Fe3O4@Au@Ag@CuxO NPs to display a sharp copper stripping peak at -0.16 V, owning to the electron transfer from Cu+ to Cu2+ and the synergistic electron transfer of Au and Ag double layers. D-AAs can be catalyzed by D-amino acid oxidase (DAAO) to produce H2O2. The autocatalytic oxidation reaction of CuxO shell with the existence of H2O2 induces the decrease of electrochemical signals of Fe3O4@Au@Ag@CuxO NPs. Fe3O4@Au@Ag@CuxO NPs served as electrochemical beacons achieve the sensitive and accurate enantioselective recognition of D-alanine (D-Ala) in the range from 100 pM to 10 μM. The limit of detection (LOD) is as low as 52 pM. This developed protocol can be extended to the fabrication of a large set of electroactive labels by the introduction of plasmonic metal NPs with high electron transfer efficiency, for the reliable enantioselective recognition with high sensitivity.

Recent advances of application of porous molecular cages for enantioselective recognition and separation.

Porous materials with well-defined pore structures have received considerable attention in the past decades due to their unique structures and wide applications. Most porous materials such as zeolites, metal-organic frameworks, covalent organic frameworks, and porous organic polymers are extended to infinite frameworks or networks by robust covalent or coordination bonds. Porous molecular cages composed of discrete molecules with permanent cavities are an emerging class of porous material and the discrete molecules assemble into solids by weak intermolecular interaction. In comparison to porous extended solids such as metal-organic frameworks and covalent organic frameworks, porous molecular cage solids are generally soluble in organic solvents thus allowing solution processing, making them more convenient to apply in many fields. This review mainly focuses on the recent advances of application of porous molecular cages (porous organic cages and metal-organic cages) for enantioselective recognition and separation from 2010 to present, including gas chromatography, capillary electrochromatography, chiral fluorescent recognition, chiral potentiometric sensing, and enantioselective adsorption. Furthermore, the two important family members of porous molecular cages, porous organic cages and metal-organic cages, are also discussed.

Facile enantioseparation and recognition of mandelic acid and its derivatives in self-assembly interaction with chiral ionic liquids.

Mandelic acid and its derivatives are important medical intermediates in the pharmaceutical industry. Different stereoisomers exhibited distinct biological properties to human bodies. Given that, enantioselective recognition and separation of mandelic acid are of great importance. In this study, four novel different types of chiral ionic liquids bearing designed functional groups were synthesized and successful enantioselective precipitation with mandelic acid and its derivatives. That is, (R, R)-chiral ionic liquid 1 can coprecipitated with S-mandelic acid and its derivatives was observed. In addition, good correlation coefficient is achieved by using electrospray mass spectrum at negative ion pattern for quick analysis of the enantioselective precipitation, which could be served as a method of enantioselective recognition. The possible intermolecular interactions are established after systematical studies by NMR spectroscopy and DFT calculations.

A chiral electrochemical system based on l-cysteine modified gold nanoparticles for propranolol enantiodiscrimination: Electroanalysis and computational modelling

Enantioselective electrochemical sensors seem to hold the promise for a fast and easy alternative for the chiral probing of bioactive molecules. However, the underlying mechanism responsible for the chiral recognition is rarely known, and suitable investigational tools are dearly missed. Therefore, as a proof-of-concept, our study is focused on investigating the interaction mechanism of the enantiomers of a chiral drug molecule, namely propranolol (PRNL) with the surface of bare and l-cysteine (l-Cys) modified gold nanoparticles employing various electrochemical techniques (differential pulse voltammetry and electrochemical impedance spectroscopy) and computational modeling (molecular dynamics simulations). If the strong surface adsorption of PRNL antipodes on bare gold nanoparticles may not be exploited for enantioselective recognition, upon the functionalization of the nanostructures with l-Cys, the almost two fold increase in the oxidation current is also accompanied by a cathodic shift (∼40 mV) of the peak potential for the S(−)-enantiomer. This peak potential shift seems to be the consequence of a favored orientation of the surface adsorbed S(−)-enantiomer towards electron transfer and/or a weaker interaction with the chiral selector and thus a higher free energy of the transient diastereoisomeric complex, in comparison with its R(+)-antipode. Computational modeling highlighted the H-bond donor and acceptor atoms of both the chiral selector (l-Cys) and adsorbates (PRNL enantiomers) responsible for the recorded enantioselective electrochemical signal. Correlations between the observed electrochemical signal and enantioselective molecular interactions occurring at the surface of the electrode may lead the way towards a more rational design of future chiral electrochemical sensing platforms.

QCM based enantioselective discrimination of enantiomers by a pair of serine derived homochiral coordination polymers

Decoding enantioselective molecular interactions between sensors and guests into readable signal represents a great challenge in developing selective sensing technology. In this work, a pair of serine derivatives based homochiral coordination polymer (HCP) enantiomers, (L)-SA-Cd and (D)-SA-Cd, were synthesized and explored as enantioselective sensors towards guest enantiomers. Quartz crystal microbalance (QCM) technology was employed to indicate the gravimetric change of (L)- and (D)-SA-Cd towards variable chiral guests, and an enantioselective factor of 1.72 ± 0.15, 1.81 ± 0.08, 1.37 ± 0.03 and 2.89 ± 0.09 were achieved for lactic acid, menthol, valinol and 1-phenylethylamine (PEA), respectively. PEA was further selected to comprehensively study the enantioselectivity via electrochemical tests, HPLC analysis and theoretical calculations. By comparison with state-of-art works, the enantioselective discrimination for PEA enantiomers is better than a vast majority of similar reports. (L)- and (D)-form of SA-Cd exhibited mirror behaviors towards guest enantiomers, and control experiments indicated the role of HCP construction in enhancing enantioselectivity. H-bonding effect was found to be the binding force between SA-Cd and PEA, as verified by FT-IR and UV–Vis titration studies. Further DFT calculations revealed the existence of conformation oriented H-bonding between the chiral –OH groups of serine fragment and –NH2 group of PEA. The findings indicate that HCP construction represents an effective strategy for promoting enantioselectivity, and monitoring gravimetric change could be a promising general method in decoding most of the enantioselective recognition process.

Enantioselective Solid-Liquid Extraction of Native Saccharides with Chiral BINOL-Based Pyridine-Phenol Type Macrocycles.

A chiral 1,1'-bi-2-naphthol (BINOL)-containing pyridine-acetylene-phenol macrocycle and a pyridine-BINOL alternating macrocycle were developed for enantioselective recognition of saccharides. In solid-liquid extraction of native saccharides, these macrocycles selectively extracted one enantiomer from each of a racemic mixture of d/l-fructose, d/l-glucose, and d/l-mannose into a lipophilic solvent. This is the first example in which native saccharides, especially such important hexoses, were enantioselectively extracted with artificial host molecules.

Electrochemical chiral sensing of tryptophan enantiomers by using 3D nitrogen-doped reduced graphene oxide and self-assembled polysaccharides.

A chiral sensor is described for the enantioselective recognition of L- and D-tryptophan (Trp). The sensor is based on the use of (a) Cu(II) ions coordinated with β-cyclodextrin (Cu-β-CD) that was self-assembled with carboxymethyl cellulose (CD-Cu-CMC) as a chiral selector, (b) of N-doped reduced graphene oxide (N-rGO) as substrate materials, and (c) of differential pulse voltammetry that was used for enantiorecognition. The 3D N-rGO was prepared by using reduced graphene oxide and pyrrole as the starting materials. Electrostatic interaction occurs between the carboxy groups of CMC and Cu(II) ions in Cu-β-CD. The FT-IR, SEM, XRD and XPS techniques showed that 3D N-rGO and the CD-Cu-CMC composite were successfully synthesized. The 3D N-rGO enabled the immobilization of the chiral selector (CD-Cu-CMC) and improves the active areas. A glassy carbon electrode was modified with N-rGO/CD-Cu-CMC and then showed a stronger electrochemical signal for L-Trp than for D-Trp, typically at a working potential of around 0.78V (vs. SCE). UV-vis spectroscopy proved that CD-Cu-CMC has a higher affinity for D-Trp. The enantioselectivity for D-Trp over L-Trp is 4.72. The modified electrode had a limit of detection of 0.063μM and 0.0035μM for L-Trp and D-Trp, respectively, with a linear response range of 0.01mM to 5mM. The sensor was used to detect Trp (D- or L-Trp) in spiked real human urine and human serum protein samples. Graphical abstract Schematic representation of an electrochemical chirality sensor based on the merits of N-rGO and CD-Cu-CMC. It involves the preparation of a chiral selector and a substrate material. N-Doped graphene oxide (N-rGO) was prepared by using graphene oxide (GO) and pyrrole as precursor. The combination of carboxymethyl cellulose (CMC) with Cu-β-CD leads to a novel self-assembly framework.