DOPA Enantiomers Research Articles

Self-Assembled Chiral Film Based on Melanin Polymers.

Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the formation of chiroptical melanin-based self-assembled films on quartz substrates, leveraging mussel-inspired surface chemistry. Water-soluble porphyrins serve as molecular synthons, facilitating the spontaneous formation of hetero-aggregates in phosphate-buffered saline containing L- or D-DOPA. Spectroscopic analysis reveals chiral transfer from DOPA enantiomers to porphyrin hetero-aggregates, followed by the disruption of these latter and subsequent generation of chiral melanin structures in solution. Quartz substrates inserted into these solutions spontaneously accumulate homogeneous melanin-like films over days, demonstrating the feasibility of self-assembly. The resulting films exhibit characteristic UV/Vis and CD spectra, with distinct signals indicating successful chiral induction. Interestingly, the AFM characterizations reveal a distinct surface morphology, and in addition, some thermal and mechanical properties have been taken into account. Overall, this study sheds light on the formation, stability, and chiroptical properties of melanin-based films, paving the way for their application in various fields.

A porous aromatic cage-based electrochemical sensor for enantioselective recognition of DOPA.

An electrochemical sensor based on porous aromatic cages was reported, which can achieve chiral sensing of DOPA enantiomers. The prepared sensor can achieve a recognition efficiency of up to 2.6 for DOPA enantiomers. The enhanced recognition efficiency could be attributed to the cooperation of intermolecular interactions, and the efficient charge transfer process.

Chiral Carbon Dots Derived from Serine with Well-Defined Structure and Enantioselective Catalytic Activity.

Carbon dots (C-Dots), with unique properties from tunable photoluminescence to biocompatibility, show wide applications in biotechnology, optoelectronic device and catalysis. Chiral C-Dots are expected to have strongly chirality-dependent biological and catalytic properties. For chiral C-Dots, a clear structure and quantitative structure-property relationship need to be clarified. Here, chiral C-Dots were fabricated by electrooxidation polymerization from serine enantiomers. The oxidized serine has a reversed chiral configuration to serine, which leads to the chiral C-Dots possessing inverse handedness compared with their raw materials. Electron circular dichroism spectrum, together with other diverse characterization techniques and theoretical calculations, confirmed that these chiral C-Dots (2-7 nm) have a well-defined primary structure of polycyclic dipeptide and possess a spatial structure with a c-axis of hexagonal symmetry and two cyclic dipeptides as the spatial structural unit. These chiral C-Dots also show enantioselective catalytic activity on DOPA enantiomers oxidation.

Chiral Fe x Cu y Se nanoparticles as peroxidase mimics for colorimetric detection of 3, 4-dihydroxy-phenylalanine enantiomers

L-3,4-dihydroxy-phenylalanine (L-dopa) is the most widely used drug in Parkinson’s disease treatment. However, development of cost-effective and high-throughput sensors to accurate enantioselective discrimination of L-dopa and D-dopa remains challenging to date. Herein, on the basis of the peroxidase-mimic activity of chiral Fe x Cu y Se nanoparticles, we demonstrated a novel colorimetric sensor for determination of chiral dopa. The surface chiral ligand, L/D-histidine (L/D-His), endowed the nanozymes with enantioselectivity in catalyzing the oxidation of dopa enantiomers. According to the values of k cat/K m, the efficiency of L-His modified nanoparticles (L-Fe x Cu y Se NPs) towards L-dopa was 1.56 times higher than that of D-dopa. While, D-His can facilely reverse the preference of the nanozyme to D-dopa. On the basis of high catalytic activity and enantioselectivity of L-Fe x Cu y Se NPs in oxidation of L-dopa, the L-Fe x Cu y Se NPs-based system can be utilized for detection of L-dopa. The linear ranges for L-dopa determination were 5 μM–0.125 mM and 0.125 mM–1 mM with a detection limit of 1.02 μM. Critically, the developed sensor has been successfully applied in the quality control of clinical used L-dopa tablets. Our work sheds light on developing simple and sensitive chiral nanomaterials-based sensors for drug analysis.

Nitrogen-Doped Chiral CuO/CoO Nanofibers: An Enhanced Electrochemiluminescence Sensing Strategy for Detection of 3,4-Dihydroxy-Phenylalanine Enantiomers.

l-3,4-Dihydroxy-phenylalanine (l-DOPA) is the most effective drug for the treatment of Parkinson's disease, which plays a very important role in clinical and neurochemistry. However, how to achieve high-sensitivity recognition of l-DOPA still faces challenges. Here, a facile strategy is presented to construct nitrogen-doped chiral CuO/CoO nanofibers (N-CuO/CoO NFs) with nanozyme activity and electrochemiluminescence property, in which CuO/CoO NFs are used as the catalytic activity center and chiral cysteine (Cys) is used as the inducer of chiral recognition, for enantioselective catalysis and sensitive recognition of DOPA enantiomers. Notably, N doping not only enhances the enzyme-mimic activity of CuO/CoO NFs but also amplifies their electrochemiluminescence (ECL) signals in the presence of luminol. More importantly, in the presence of DOPA enantiomers, the d-cysteine (d-Cys)-modified N-CuO/CoO NFs exhibit different ECL performances; thus, d-Cys@N-CuO/CoO NFs could selectively distinguish and sensitively detect l-DOPA through ECL signals, and the detection limit is 0.29 nM for l-DOPA. In addition, it also showed good sensing performance for the determination of l-DOPA in fetal bovine serum. This is the first report on the detection of DOPA enantiomers based on an enhanced ECL strategy, providing a robust pathway for chiral discrimination and detection of chiral molecules.

L-Pyroglutamic Acid-Modified CdSe/ZnS Quantum Dots: A New Fluorescence-Responsive Chiral Sensing Platform for Stereospecific Molecular Recognition

Stereoselective recognition of amino acids is extremely important due to its high chirality-dependent interactions and physiological activities in life activities. We herein report a novel functionalized chiral fluorescent nanosensor prepared from surface modification of CdSe/ZnS quantum dots (QDs) with pyroglutamic acid derivatives, which could serve as a chiral recognition module for fluorescence detection of chiral molecules. The sensor exhibited a unique stereoselective fluorescence response to histidine (His), glutamate (Glu), and dihydroxyphenylalanine (Dopa) and had preferable response performance to l-enantiomers. The enantiomeric fluorescence difference ratios of His, Glu, and Dopa enantiomers were 3.90, 3.40, and 2.49, respectively. The mechanism for the enantiomeric fluorescence recognition was systematically studied through a fluorescence spectrum, fluorescence life, and density functional theory (DFT) calculation. Presumably, the different hydrogen bonding capacity of the chiral recognition module with two enantiomers mainly contributed to the difference in fluorescence signals. As a result, a broader application of the pyroglutamic acid derivative-coated QDs as a fluorescence-responsive chiral sensing platform for enantiomeric detection would be expected.

A Stereoselective Tyrosinase Model Compound Derived from an m-Xylyl-l-histidine Ligand.

The aim of mimicking enzyme activity represents an important motivation for the development of new catalysts. A challenging objective is the development of chiral complexes for bioinspired enantioselective oxidation reactions. Herein, we report a new chiral dinuclear copper(II) complex based on a m-xylyl-bis(histidine) ligand (mXHI) as a biomimetic catalyst for tyrosinase and catechol oxidase. The new ligand improves a previous system also containing two tridentate N3 units derived from l-histidine that were connected by a short, rigid ethanediamine bridge. In mXHI the bridge is provided by the more extended m-xylyl moiety. The dicopper(II) complex [Cu2(mXHI)]4+ was studied as a catalyst for stereoselective oxidations of enantiomeric couples of chiral catechols of biological interest (L/D-dopa, L/D-dopa methyl ester, and ( R/ S)-norepinephrine), showing excellent discrimination capability, particularly for the methyl esters of dopa enantiomers. The catechol oxidation was studied in acetate buffer as slightly acidic medium, and a role of acetate as bridging ligand between the two coppers, preorganizing the dinuclear center in a more catalytic efficient structure, could be established. The oxidation of β-naphthol and 3,5-ditertbutylphenol was studied as a model monophenolase reaction. The oxidation proceeds stoichiometrically, and the partial incorporation of 18O into β-naphthol when the reaction was performed using 18O2 suggests the existence of two competitive reaction pathways, a genuine monooxygenase mechanism and a radical pathway. However, the more challenging reaction on derivatives of l-/d-tyrosine did not lead to the desired monooxygenase product but only to products of radical oxidation. Complex [Cu2(mXHI)]4+ was also used for the catalytic sulfoxidation of thioanisole in the presence of hydroxylamine as cosubstrate, in a preliminary attempt to model the reaction of external monooxygenases. The reaction proceeds with 25 turnovers, but the enantiomeric excess of sulfoxide was modest.

Boc-phenylalanine Grafted Poly(3,4-propylenedioxythiophene) Film for Electrochemically Chiral Recognition of 3,4-Dihydroxyphenylalanine Enantiomers

To prepare chiral monomer with single chiral center and higher stereospecificity, a pair of amino-functionalized chiral 3,4-propylenedioxythiophene (ProDOT) derivatives, chiral (3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl) amino]-3-phenylpropanoate (ProDOT-Boc-Phe), were synthesized. Chiral poly[(3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate] (PProDOT-Boc-Phe) modified electrodes were synthesized via potentiostatic polymerization of chiral ProDOT-Boc-Phe. Chiral PProDOT-Boc-Phe films displayed good reversible redox activities. The enantioselective recognition between chiral PProDOT-Boc-Phe modified glassy carbon electrodes and DOPA enantiomers was achieved by different electrochemical technologies, including cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV). (D)-PProDOT-Boc-Phe and (L)-PProDOT-Boc-Phe showed higher peak current responses toward L-DOPA and D-DOPA, respectively.

Chiral Sensing with Mesoporous Pd@Pt Nanoparticles

AbstractMesoporous Pd@Pt nanoparticles possess high surface areas while still maintaining electroconductivity and low potential for agglomeration. By introducing L‐ or D‐DOPA (3,4‐dihydroxyphenylalanine) enantiomers during the synthesis of the mesoporous Pd@Pt nanoparticles, we can create a Pt shell that is sensitive to the chirality of the DOPA molecule. We demonstrate sensitive electrochemical detection of DOPA enantiomers.

Discriminative sensing of DOPA enantiomers by cyclodextrin anchored graphene nanohybrids

Discriminative sensing of chiral species with a convenient and robust system is a challenge in chemistry, pharmaceutics and particularly in biomedical science. Advanced nanohybrid materials for discrimination of these biologically active molecules can be developed by combination of individual obvious advantages of different molecular scaffolds. Herein, we report on the comparison of the performance of cyclodextrin functionalized graphene derivatives (x-CD/rGO, x: α-, β-, γ-) for discrimination of DOPA enantiomers. Within this respect, electrochemical measurements were conducted and the experimental results were compared to molecular docking method. Thanks to cavity size of γ-CD and the unique properties of graphene, rGO/γ-CD nanohybrid is capable of selective recognition of DOPA enantiomers. Limit of detection (LOD) value and sensitivity were determined as 15.9 μM and 0.2525 μA μM−1 for D-DOPA, and 14.9 μM and 0.6894 μA μM−1 for L-DOPA.

Enantioselective Recognition of DOPA by Mesoporous Platinum Imprinted with Mandelic Acid

AbstractChiral imprinted mesoporous platinum was electrochemically synthesized in the presence of mandelic acid and Brij 56 surfactant as chiral and mesoporous templates, respectively. The chiral cavity obtained by using mandelic acid as a template can be used to distinguish between enantiomers of other chiral molecules in which the stereocentre has a correlated configuration with respect to the imprinted one. This recognition versatility was tested for the discrimination of DOPA enantiomers. Mesoporous platinum electrodes imprinted with (R)‐mandelic acid preferentially react with L‐DOPA and vice versa for the (S)‐mandelic acid imprinted one, which is more reactive for D‐DOPA.

Study on Chiral Nanocomposite for Recognition of DOPA Enantiomers via Square Wave Voltammetry

An electrochemical sensor was explored for recognizing 3,4-dihydroxyphenylalanine (DOPA) enantiomers based on L-cysteine covalently binding with the multi-walled carbon nanotubes functionalized with 3,4,9,10-perylene tetracarboxylic acid (MWCNTs-PTCA-Cys). Here two different ways of square wave voltammetry (SWV) and cyclic voltammetry (CV) were utilized to investigate the stereospecific interaction between the MWCNTs-PTCA-Cys nanocomposite and DOPA enantiomers. The D-DOPA and L-DOPA exhibited different response in both CV and SWV, in addition, the difference in SWV was more obvious and reached to 264.9 μA, suggesting that the enantiomers could be successfully distinguished by MWCNTs-PTCA-Cys nanocomposite, and the selection of electrochemical technique played an important role in enantioselective recognition. Under the optimum conditions, the detection limits of D-DOPA and L-DOPA were 2.5 μM and 4.6 μM (S/N = 3), respectively, with a linear range of 1.0 × 10−5 M to 5.0 × 10−3 M. This work provided a simple method to recognize and determine DOPA enantiomers with rapid response, excellent recognition ability, high sensitivity and good stability.

The application of l-tryptophan functionalized graphene-supported platinum nanoparticles for chiral recognition of DOPA enantiomers

A carbon-based nanocomposite surface was prepared to develop a simple strategy for electrochemical chiral analysis.

Evaluation of scavenging rate constants of DOPA and tyrosine enantiomers against multiple reactive oxygen species and methyl radical as measured with ESR trapping method.

The scavenging rates of DOPA (dl- and l-3-(3,4-dihydroxyphenyl)alanine) and Tyr (tyrosine (dl- and l-3-(4-hydroxyphenyl)alanine)) against five reactive oxygen species (ROS) and methyl radical were measured with the use of electron spin resonance (ESR) spin-trapping method and the scavenging rate constants of DOPA and Tyr were determined. The scavenging rate constants for multiple active species increased in the order of O2(-)<RO<(1)O2<H3C<HO for Tyr and RO≈O2(-)<(1)O2≈H3C<HO for DOPA, and the differences in the radical scavenging abilities for l-enantiomers and dl-mixtures of DOPA and Tyr were shown. Further, based on the redox potentials, we have suggested that the primary chemical process of antioxidant reactions with O2(-) and (1)O2 can be characterized with the electron transfer of antioxidants (DOPA and Tyr).

A chiral sensor for recognition of DOPA enantiomers based on immobilization of β-cyclodextrin onto the carbon nanotube-ionic liquid nanocomposite

A sensitive electrochemical method was explored for chiral recognition of 3,4-dihydroxyphenylalanine (DOPA) enantiomers based on immobilization of β-cyclodextrin (β-CD) onto the nanocomposite comprising multiwalled carbon nanotubes (MWCNTs) and ionic liquid (IL) 1-butyl-3-methylimidazolium hexafluorophosphate (BIMIMPF6) modified glassy carbon electrode (β-CD/MWCNTs-IL/GCE). The combination of ionic liquid and carbon nanotubes could create unique nanomaterials which facilitated the electron transfer. In addition, β-CD was brought in to act as the chiral selector for DOPA enantiomers recognition. The immobilization process of β-CD/MWCNTs-IL/GCE was monitored by cyclic voltammetry, electrochemical impedance spectroscopy, and scanning electron microscopy. The chiral interface (β-CD/MWCNTs-IL/GCE) was employed to discriminate DOPA enantiomers via differential pulse voltammetry. The results indicated that the proposed sensor exhibited a stronger electrochemical response toward D-DOPA over the linear range from 4.0 × 10−3 to 4.0 × 10−9 mol L−1 and the detection limit was 1.2 × 10−9 mol L−1 (S/N = 3). This work provided an available platform for enantioselective recognition of DOPA enantiomers based on the nanocomposite.

Enantiomeric Determination of DOPA in Dietary Supplements Containing &lt;i&gt;Mucuna pruriens&lt;/i&gt; by Liquid Chromatography/Mass Spectrometry

We developed a simple and rapid liquid chromatography/mass spectrometry (LC/MS) method for the enantiomeric determination of DOPA in dietary supplements containing Mucuna pruriens. L- and D-DOPA were ultrasonically extracted with 1% formic acid aqueous solution. The isolated extracts were analyzed by LC/MS using a Crownpak CR (-) column at 30℃. The mass spectrometer was operated in the positive mode of electrospray ionization, and the mobile phase was aqueous formic acid (pH 2.0). L-DOPA-ring-d3 was used as an internal standard. The method was validated for a dietary supplement spiked with L- and D-DOPA at 50 and 500 μg/g, respectively, and the recoveries of the DOPA enantiomers were between 97.5% and 101.3%. Relative standard deviation values of repeatability and intermediate precision were less than 7%. The method was applied to 14 dietary supplements. L-DOPA was detected in these supplements in the range of 0.88-12.8 mg/unit. D-DOPA was not detected.

A fast chiral sensing to DOPA enantiomers via poly-lysine films matrixes

Abstract A fast electrochemical sensing to recognize 3,4-dihydroxyphenylalanine (DOPA) enantiomers was proposed based on poly-lysine enantiomers films as matrixes, which were electrodeposited on the surface of glass carbon electrodes via cyclic voltammetry (CV). Differential pulse voltammetry (DPV) and CV were employed to investigate the stereospecific recognition of DOPA enantiomers. The concentration of l -lysine, electro-polymerization cycles, pH and the effect of the temperature on the chiral discrimination were investigated to obtain optimization of the experimental parameters, and the Gibbs’ free energy (ΔG) was also discussed. The results showed that not only DOPA enantiomers could be recognized by poly-lysine matrix with the tendency of heterochiral interaction between poly-lysine and DOPA enantiomers, but also the largest discrimination responses were resided in poly- l -lysine matrix (PLL) and d -DOPA with the measurement range of 5.0 × 10−7 M to 8.0 × 10−3 M. The detection limit was 0.17 μM (S/N = 3), and the detection time only spent 75 s. The simple method with rapid recognition, good sensitivity and high stability provided a new perspective to recognize and determine DOPA enantiomers with fast, stabile, selective characteristics.

Enantioselective Recognition of Dopa Enantiomers in the Presence of Ascorbic Acid or Tyrosine

AbstractA simple sensor was obtained through N‐isobutyryl‐L‐(D)‐cysteine enantiomers self‐assembled monolayer. It was demonstrated that the N‐isobutyryl‐cysteine modified gold electrodes can enantioselectively recognize 3,4‐dihydroxyphenylalanine (dopa) enantiomers. The electrocatalytic behaviors of enantiomers were analyzed with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Selectivity of the chiral surface was estimated by investigating two mixture enantiomers (dopa‐ascorbic acid and dopa‐tyrosine), it certified that the sensor was only satisfactorily used to specific recognize dopa enantiomers. The possible mechanism for the enantioselective recognition was discussed.

Simultaneous determination of dopa and carbidopa enantiomers by capillary zone electrophoresis.

Dopa and carbidopa, components of the dual therapy for Parkinson's disease treatment, are both provided as single enantiomers, since their D-forms are inactive. To ensure the efficiency and safety of the therapy, these D-enantiomers, therefore, should be considered as impurities. In this paper, the enantioseparation power of different types of cyclodextrins, both neutral and charged ones, on dopa and carbidopa enantiomers was tested. Three methods of simultaneous separation of dopa and carbidopa enantiomers were developed, using highly sulfated beta-cyclodextrin and sulfated beta-cyclodextrin as chiral selector, in normal and reversed polarity mode. Two methods among these three were found sensitive enough for the quantitation of 0.1% D-enantiomers in L-forms (impurity level). After the optimization study, the best method was selected, using 16 mM sulfated beta-cyclodextrin in 15 mM sodium phosphate buffer pH 2.45, an uncoated fused-silica capillary (50 num inner diameter, 30 cm total length), and an applied voltage of -12 kV. This method is robust and efficient, with very high resolution for all peaks within a short analysis time of 10 min. Quantitatively, the method offers a limit of detection (LOD) of 0.2 nug/mL and a limit of quantitation (LOQ) of 0.5 nug/mL for both D-dopa and D-carbidopa, which is equivalent to 0.02% and 0.05% against the respective L-enantiomers. A linear relationship was found between the concentration of the analyte and the corresponding peak area in a range of 0.5-2.0 nug/mL.

Enantioseparation of 3,4-dihydroxyphenylalanine and 2-hydrazino-2-methyl-3-(3,4-dihydroxyphenyl)propanoic acid by capillary electrophoresis using cyclodextrins

The enantiomeric separations of 3,4-dihydroxyphenylalanine (dopa) and 2-hydrazino-2-methyl-3-(3,4-dihydroxyphenyl)propanoic acid (carbidopa) by capillary electrophoresis were studied using several native, neutral and anionic cyclodextrins as chiral additives and uncoated fused-silica capillaries. The effect of the type and concentration of the cyclodextrin added to 20 m M phosphate buffer (pH 2.5) on enantioseparation and migration times was studied. A high resolution value of 15.63 was obtained for dopa enantiomers with a buffer containing 20 m M single isomer, heptakis(2,3-diacetyl-6-sulfato)-β-cyclodextrin. The enantiomers of carbidopa were separated using 20 m M carboxymethyl-β-cyclodextrin as a chiral resolving agent. Both methods allowed the determination of 0.1% of the d-enantiomer (second migrating) in the presence of the l-enantiomer (first migrating) of dopa and carbidopa with a good precision. These methods also gave good results in terms of precision for both peak area, migration time, linearity and accuracy.