Enantioselective Fluorescence Enhancement Research Articles

Novel Chiral Self-Assembled Nano-Fluorescence Materials with AIE Characteristics for Specific Enantioselective Recognition of L-Lysine.

In this paper, two aggregation-induced emission (AIE) chiral fluorescent materials, S-1 and S-2, were synthesized. The two materials are based on BINOL and H8-BINOL backbones, respectively, and large electron-absorbing groups are attached to the chiral backbones through the Knoevenagel reaction. At the same time, the CD signals of these two chiral fluorescent materials are gradually weakened (fw gradually increases) as they continue to aggregate. However, S-2 underwent a flip-flop from a negative to positive chiral CD signal at fw ≥ 90. And both materials also showed significant enantioselective recognition of lysine, demonstrating their potential as novel chiral fluorescent probes. Among them, the enantioselective fluorescence enhancement ratios (ef) of S-1 and S-2 for lysine were 10.0 and 10.3, respectively, while different degrees of blue shifts were produced by the ICT mechanism during the recognition process. In addition, the self-assembled morphology of the two nanomaterials is different; S-1 comprises hollow-core vesicles that are more likely to aggregate to form larger self-assembled vesicles, whereas S-2 is a solid block structure. When L/D-lysine was added alone, the morphology of S-1 was more distinctly different compared to S-2. With the addition of L-lysine, S-1 was dispersed and regularly spherical, whereas with the addition of D-lysine, S-1 itself remained in the form of aggregated large vesicles. This suggests that both S-1 and S-2 are important in the fields of chiral optics, chiral recognition, and nanoscale self-assembly.

Synthesis of novel fluorescence probes and their application in the enantioselective recognition of arginine.

Arginine (Arg) plays a crucial and multifaceted role in various biological processes, encompassing cell division, wound healing, immune system modulation, and plant signaling. This study introduced a pair of novel chiral fluorescent probes, (R)-5 and (S)-5, constructed upon the BINOL framework, which exhibited enantiomeric selectivity and sensitivity to d-Arg/l-Arg in fluorescence experiments. These probes offered a simple, rapid, low-cost, and highly selective method for detecting Arg enantiomers, thereby providing a highly sensitive approach for their qualitative and quantitative analysis. The enantioselective fluorescence enhancement ratios {ef = [(I1 - I0)/(I2 - I0) = ΔI1/ΔI2]} of (R)-5 and (S)-5 to Arg were 1694 and 5163, respectively. Moreover, the probes demonstrated the capability to detect the concentration of d-Arg and l-Arg with a limit of detection of 4.84 × 10-7 M and 3.35 × 10-7 M, respectively, as well as determine the enantiomeric excess. These probes exhibited high chemical selectivity and enantioselectivity, enabling the identification of different configurations of Arg, quantification of Arg concentrations, and determination of the enantiomeric composition of Arg. This study provides valuable insights for the development of sensitive and selective chiral molecular detection methods, significantly advancing our comprehension of the relationship between Arg concentration and probe fluorescence response.

Enantioselective Fluorescence Recognition of Free α-Amino Acids by Ion-Type Ammonium Salt-Based Sensors.

Optically pure amino acids have extensive applications in pharmaceuticals, pesticides, food, materials, and other fields. Enantiomers recognition of chiral amino acids using optical methods with synthetic chiral sensors has attracted extensive attention. Most reported sensors typically identify guests by covalent or hydrogen bonding or hydrophobic interaction with amino acids and their derivatives. In this paper, a series of ion-type quaternary ammonium salt-based enantioselective fluorescent sensors were synthesized for chiral recognition of free α-amino acids via electrostatic interaction. The fluorescence intensity ratios ID/IL (ID, IL, fluorescence intensity of sensor when treated with D- or L-amino acid) were up to 2.1 and enantioselective fluorescence enhancement ratios ef (ef=[IL-I0]/[ID-I0] or [ID-I0]/[IL-I0]. (I0, fluorescence intensity of the sensor)) were up to 5.0. Among them, sensor 3 showed best enantioselective recognition performance toward tryptophan (Trp), and L-Trp significantly quenched the fluorescence of sensor 3, but D-Trp greatly enhanced the fluorescence of sensor 3, its ID/IL was 2.11 and ef was 1.8. The mechanistic investigation by NMR spectrum revealed that a tight three-point interaction, including electrostatic interaction, hydrogen bond, and π-π stacking, between sensor 3 and D-Trp was formed.

Near-IR Fluorescent Recognition of Arginine: High Chemoselectivity and Enantioselectivity Promoted by La3.

The first near IR fluorescent probe for the chemoselective and enantioselective recognition of arginine in aqueous solution is reported in this work. This probe, made of a 1,1'-binaphthyl-based chiral aldehyde unit and a rhodamine-based near IR chromophore, in combination with La3+ exhibits highly chemoselective as well as enantioselective fluorescent enhancement with arginine at λ=764 nm upon excitation at λ=690 nm. Little or no fluorescent response is observed toward the chirality miss-matched arginine enantiomer or other common amino acids and their enantiomers. This probe also allows visual discrimination of the arginine enantiomers because of its fast and distinct color change upon interaction with the substrate.

One Molecular Probe with Opposite Enantioselective Fluorescence Enhancement at Two Distinct Emissions.

It is discovered that one enantiomer of a chiral substrate can greatly enhance the fluorescence of one molecular probe at one emitting signal (λ1 = 517 nm), while the opposite enantiomer of the substrate greatly enhances the fluorescence of the same probe at a distinctively different emission (λ2 = 575 nm). This probe is made of a 1,1'-binaphthyl-based chiral dialdehyde that in combination with Zn2+ under slightly acidic conditions shows a chemoselective and enantioselective fluorescent response to histidine. The opposite enantioselective fluorescent responses of the probe at two emissions allow it to be used to determine both the concentration and the enantiomeric composition of the substrate using a single probe. The mechanistic study has revealed two very different reaction pathways when the two enantiomers of the substrate are treated with the probe. These reaction pathways generate two different products, one dimeric and another polymeric, with very different emissions.

Enantioselective Recognition of L-Lysine by ICT Effect with a Novel Binaphthyl-Based Complex.

A novel triazole fluorescent sensor was efficiently synthesized using binaphthol as the starting substrate with 85% total end product yield. This chiral fluorescence sensor was proved to have high specific enantioselectivity for lysine. The fluorescence intensity of R-1 was found to increase linearly when the equivalent amount of L-lysine (0-100 eq.) was gradually increased in the system. The fluorescence intensity of L-lysine to R-1 was significantly enhanced, accompanied by the red-shift of emission wavelength (389 nm to 411 nm), which was attributed to the enhanced electron transfer within the molecular structure, resulting in an ICT effect, while the fluorescence response of D-lysine showed a decreasing trend. The enantioselective fluorescence enhancement ratio for the maximum fluorescence intensity was 31.27 [ef = |(IL - I0)/(ID - I0)|, 20 eq. Lys], thus it can be seen that this fluorescent probe can be used to identify and distinguish between different configurations of lysine.

Enantioselective Recognition of Lysine and Phenylalanine Using an Imidazole Salt-Type Fluorescent Probe Based on H8-BINOL

An imidazole bromide fluorescent probe (R)-1 based on chiral H8-BINOL was synthesized with a high yield; it was found to have good enantioselective recognition of lysine and phenylalanine using fluorescence analysis. When L-lysine was recognized, the enantioselective fluorescence enhancement ratio was 2.7 (ef = IL - I0/ID - I0, ef = 2.7, 20 eq Lys); as the amount of L-Lys increased, a distinct red shift was observed (the wavelength varied by 55.6 nm, 0-100 eq L-Lys), whereas D-Lys had a minimal red shift. The generation of this red shift phenomenon was probably due to the ICT effect; the probe's intramolecular charge transfer was affected after (R)-1 bound to L-Lys, and this charge transfer was enhanced, leading to a red shift in fluorescence. In addition to the enantioselective recognition of lysine, phenylalanine was also recognized; the enantioselective fluorescence enhancement ratio was 5.1 (ef = IL - I0/ID - I0, ef = 5.1, 20 eq Phe).

Enantioselective fluorescent detection of lysine enantiomers by functionalized achiral metal organic frameworks

In this work, achiral metal organic frameworks (MIL-53(Al)–NH2) were synthesized and functionalized with poly (amidoamine) (PAMAM) dendrimers. By dispersing PAMAM grafted MIL-53(Al)–NH2 to water, the obtained solution exhibited high fluorescence intensity and stability. Due to the strong affinity interaction, fluorescence of the solution was quenched when Cu2+ was added. Following the addition of lysine to the system, the quenched fluorescence intensity was partially restored based on the chelation between Cu2+ and lysine. In this case, the fluorescent signal of MIL-53(Al)–NH2-PAMAM-Cu2+ system became turn-on state. Furthermore, because of different chelating abilities with L-lysine and D-lysine, the system exhibited enantioselective fluorescence enhancement. Therefore, the PAMAM grafted MIL-53(Al)–NH2 were successfully used for enantioselective fluorescence detection of lysine after being quenched by Cu2+. The method showed good linearity in both L/D-lysine detection (R2 = 0.9976–0.9984) and ee values determination (R2 = 0.9921). The detection limit of L-lysine and D-lysine were 7.52 and 12.2 μmol L−1, respectively. Reliability of the method was verified by analysis of lysine enantiomers in spiked drinking water samples. Rapid enantioselective fluorescent imaging of lysine enantiomers showed great application prospects in test paper, diagnostic kit and vivo imaging system.

Enantioselective Fluorescent Recognition of β‐Amino Alcohols by Stereoselective Cyclization

Abstract2,2’‐Diformyl‐1,1’‐binaphthyl is found to exhibit highly enantioselective fluorescence enhancement in the presence of various β‐amino alcohols and base. It provides a new method to determine the enantiomeric composition of those substrates and has potential for high throughput analysis. Based on detailed spectroscopic analyses, it is proposed that a stereoselective cyclization of a β‐amino alcohol with the probe should occur to form a rigid macrocyclic intermediate, contributing to the greatly enhanced fluorescence.

Chiral fluorescent sensor based on H8-BINOL for the high enantioselective recognition of d- and l-phenylalanine.

Phenylalanine an essential aromatic amino acid for humans and animals, cannot be synthesized by humans and animals on their own. However, it synthesizes important neurotransmitters and hormones in the body and is involved in gluconeogenesis and lipid metabolism. Moreover, the two opposite configurations of phenylalanine have different activities. For example, l-phenylalanine is a biologically active optical isomer involved in crucial biological processes, the lack of which will lead to intellectual disability, while d-phenylalanine only acts as a chiral intermediate. In this research, an H8-BINOL chiral fluorescent sensor modified with 1,2,3-triazole was synthesized in high yield (95%) by nucleophilic substitution and click reaction. The chiral fluorescent sensor showed high enantioselectivity toward phenylalanine. l-Phenylalanine enhanced the fluorescence response of the probe significantly, while d-phenylalanine had no obvious fluorescence response change. The enantioselective fluorescence enhancement ratio [ef = (IL − I0)/(ID − I0), where I0 is the fluorescence of the sensor without amino acids] for the highest fluorescence intensity at 20.0 equivalents of amino acids was 104.48. In this way, the probe could be used to identify and differentiate different configurations of phenylalanine.

Semiquantitative Visual Chiral Assay with a Pseudoenantiomeric Fluorescent Sensor Pair.

A new red-light-emitting fluorescent probe (R)-5 was synthesized. In the presence of Zn2+, this compound was found to exhibit good enantioselective fluorescence enhancement at λ = 655 nm when treated with a variety of amino acids in aqueous solution. This probe in combination with a green-light-emitting probe (S)-4 that has enantioselective fluorescence enhancement at λ = 505 nm has formed a pseudoenantiomeric sensor pair because of their opposite enantioselectivities. This sensor pair can simultaneously detect both enantiomers of a chiral amino acid at two very different wavelengths (Δ = 150 nm). It was used to visually and semiquantitatively determine the enantiomeric compositions of amino acids. For example, when a 1:1 mixture of (R)-5 and (S)-4 was treated with Zn(OAc)2 and histidine samples of 0-100% [d-His], the color of the mixtures changed from green to yellow, orange, and red under a UV lamp (365 nm), which allowed a quick quantification of [d-His]%. This is the first example of using fluorescence to visually quantify the enantiomeric composition of chiral compounds.

Enantioselective Sensing in the Fluorous Phase for Catalyst Screening: Application of a Racemic Fluorescent Probe.

A perfluoroalkyl ketone-based molecular probe was found to show highly enantioselective fluorescent enhancement in the fluorous phase when treated with an amino alcohol generated from the asymmetric reaction of a meso-epoxide with an alkyl amine. The two enantiomeric probes (R)- and (S)-2 were used to screen catalysts for this asymmetric reaction. The use of the probe in the fluorous phase allowed the fluorescent sensing of the products to be conducted away from the other reaction components with minimized interference. It was further found that when (R)- or (S)-2 was used to determine the enantiomeric composition of the amino alcohol product, there was a large nonlinear effect. That is, only when one enantiomer of the substrate was in excess was there a large fluorescence enhancement for the chirality-matched probe-substrate interaction. This allowed the racemic probe rac-2 to be used to evaluate the asymmetric induction in the catalyst screening. The catalyst screening using the fluorescent probes led to the discovery of a more enantioselective and efficient method for the desymmetrization of 1,2-epoxycyclohexane with iPrNH2 to form the corresponding chiral amino alcohol. This work presents a novel method to conduct catalyst screening for asymmetric synthesis and has potential to become a high-throughput process.

Highly chemoselective and enantioselective recognition of serine by a fluorescent probe

A diarylacetylene-containing 1,1′-bi-2-naphthol derivative (R)-2 was designed and synthesized. This compound in combination with Zn2+ represents the first chemoselective as well as enantioselective fluorescent probe for the biologically important amino acid serine. It was found that l-serine can greatly enhance the fluorescence of the probe at λ = 471 nm but d-serine and 17 other common amino acids cannot. An enantioselective fluorescence enhancement ratio [ef = (IL − I0)/(ID − I0) = ΔIL/ΔID] of 15 was observed for the response of (R)-2 + Zn2+ toward serine.

Fabrication of a "turn-on"-type enantioselective fluorescence sensor via a modified achiral MOF: applications for synchronous detection of phenylalaninol enantiomers.

Homochiral metal-organic frameworks (HMOFs) have garnered considerable attention due to their extrachiral properties and broad application for chiral recognition. However, assembling a pair of high-quality chiral MOFs for sensing enantiomers precisely is a formidable challenge because of the complicated chiral environment and uncontrollable coordinated conditions. Herein, one pair of homochiral UiO-66 analogues, S-1 (l-AP@UiO-66-(COOH)2) and R-1 (d-AP@UiO-66-(COOH)2), are reported for chiral recognition. They were fabricated via a condensation reaction between the carboxyl groups of UiO-66-(COOH)2 and amino groups of l/d-amino propanol (l/d-AP). These novel fluorescent probes exhibited highly enantioselective fluorescence enhancement towards l/d-phenylalaninol (l/d-PA). For example, when S-1 and R-1 were treated with l-PA or d-PA, they displayed different fluorescence responses: the enantiomeric fluorescence enhancement ratio (ef) was 2.51 and 0.41 for S-1 and R-1, respectively. Hence, a visible difference in fluorescence enhancement for l-PA and d-PA and excellent enantioselective behavior between S-1 and l-PA (or R-1 and d-PA) was displayed. Measurements of fluorescence lifetime, powder X-ray diffraction, molecular-dynamic simulations and Benesi-Hildebrand plots were employed to determine the observed high enantioselectivity for l/d-PA. In brief, we found that two post-modified HMOFs, S-1 and R-1, were outstanding enantioselective sensors for detecting l-PA and d-PA. They had a prominent difference in ef and remarkable enantioselectivity factor α and ΔΔG based on steric hindrance and stereochemical difference.

Sulfonation of 3,3'-Diformyl-BINOL for Enantioselective Fluorescent Recognition of Amino Acids in Water.

Reaction of (R)-3,3'-diformyl-1,1'-bi-2-naphthol with concentrated sulfuric acid gives the corresponding 6,6'-disulfonated compound (R)-2 selectively. This provides a simple and efficient method to convert a water-insoluble compound to a water-soluble fluorescent probe. It is found that (R)-2 in combination with Zn2+ shows a highly enantioselective fluorescent response toward various amino acids in the aqueous HEPES buffer solution at pH 7.4. For example, an enantioselective fluorescence enhancement ratio [ef=ΔID /ΔIL ] up to 35.8 is observed for the recognition of asparagine. NMR and mass spectroscopic investigations are conducted to explore the reaction of (R)-2 with asparagine.

Fluorescent recognition of l- and d-tryptophan in water by micelle probes

A series of BINOL-based monoaldehydes in the presence of a diblock copolymer PEG-PLLA are encapsulated into micelles in water which in combination with Zn2+ have exhibited chemo- and enantioselective fluorescence enhancement with tryptophan.

Excitation of One Fluorescent Probe at Two Different Wavelengths to Determine the Concentration and Enantiomeric Composition of Amino Acids.

When a novel fluorescent probe made of BINOL and coumarin is excited at λ1 = 365 nm in a neutral buffer solution, it shows fluorescence enhancement at 465 nm in the presence of an amino acid with a very small difference between the two enantiomers. When excited at λ2 = 467 nm, it shows highly enantioselective fluorescence enhancement at 534 nm. This allows the determination of both concentration and enantiomeric composition of amino acids.

Micelle-Encapsulated Fluorescent Probe: Chemoselective and Enantioselective Recognition of Lysine in Aqueous Solution.

A diblock copolymer, poly(ethylene glycol) methyl ether- block-poly(l-lactide), is used to solubilize 3,3'-diformylBINOL ( S)-1 in water to make the micelle-encapsulated fluorescent probe M L- S1. It was found that M L- S1 was able to recognize d-lysine chemoselectively as well as enantioselectively among 19 amino acids and their enantiomers in carbonate buffer. The enantioselective fluorescence enhancement ratio [ef = ( ID - I0)/( ID - I0) = Δ ID/Δ IL] up to 6.6 was observed for the response of M L- S1+Zn(II) toward lysine.

Racemic Fluorescence Probe for Enantiomeric Excess Determination: Application of Cononsolvency of a Polymer in Sensing.

Both racemic and optically active 3,3'-diformyl-1,1'-BINOL-based diinitiators (BINOL = 1,1'-bi-2-naphthol) were used to carry out the atom transfer radical polymerization (ATRP) of N-isopropylacrylamide to make polymers rac-1, ( R)-1, and ( S)-1 which are soluble in water as well as organic solvents. These polymers are found to exhibit a unique cononsolvency property. Mixing an aqueous solution of a polymer and Zn2+ with a dichloromethane solution of ( S)- or ( R)-amino alcohols led to the formation of polymer films at the interface of the water and dichloromethane phases. The polymer films were separated and showed highly enantioselective fluorescence enhancement in DMSO solution. When the polymers were treated with a mixture of the enantiomers of an amino alcohol, no fluorescence enhancement was observed unless one of the enantiomers was in excess of the other. Such a large nonlinear effect allows the racemic polymer rac-1 to be used to determine the ee of the amino alcohol. This represents the first example to use a racemic fluorescent probe to determine the ee of a chiral molecule.

Free Amino Acid Recognition: A Bisbinaphthyl-Based Fluorescent Probe with High Enantioselectivity.

A novel fluorescent probe based on a bisbinaphthyl structure has been designed and synthesized. This compound in combination with Zn(II) has exhibited highly enantioselective fluorescence enhancement with 13 common free amino acids. For example, its enantiomeric fluorescent enhancement ratios ( ef or Δ IL/Δ ID) in the presence of the following amino acids are extremely high: 177 for valine, 199 for methionine, 186 for phenylalanine, 118 for leucine, and 89 for alanine. The observed high enantioselectivity and the extent of the substrate scope are unprecedented in the fluorescent recognition of free amino acids. This fluorescent probe can be applied to determine the enantiomeric composition of the structurally diverse chiral amino acids. NMR and mass spectroscopic investigations have provided clues to elucidate the observed high enantioselectivity.