Naproxen Enantiomers Research Articles

Enantioselective Molecular Detection by Surface Enhanced Raman Scattering at Chiral Gold Helicoids on Grating Surfaces.

Distinct advantages of surface enhanced Raman scattering (SERS) in molecular detection can benefit the enantioselective discrimination of specific molecular configurations. However, many of the recent methods still lack versatility and require customized anchors to chemically interact with the studied analyte. In this work, we propose the utilization of helicoid-shaped chiral gold nanoparticles arranged in an ordered array on a gold grating surface for enantioselective SERS recognition. This arrangement ensured a homogeneous distribution of chiral plasmonic hot spots and facilitated the enhancement of the SERS response of targeted analytes through plasmon coupling between gold helicoid multimers (formed in the grating valleys) and adjacent regions of the gold grating. Naproxen enantiomers (R(+) and S(-)) were employed as model compounds, revealing a clear dependence of their SERS response on the chirality of the gold helicoids. Additionally, propranolol and penicillamine enantiomers were used to validate the universality of the proposed approach. Finally, numerical simulations were conducted to elucidate the roles of intensified local electric field and optical helicity density on the SERS signal intensity and on the chirality of the nanoparticles and enantiomers. Unlike previously reported methods, our approach relies on the excitation of a chiral plasmonic near-field and its interaction with the chiral environment of analyte molecules, obviating the need for the enantioselective entrapment of targeted molecules. Moreover, our method is not limited to specific analyte classes and can be applied to a broad range of chiral molecules.

Robust Homochiral Polycrystalline Metal-Organic Framework Membranes for High-Performance Enantioselective Separation.

Homochiral MOF membranes offer a promising route to efficient chiral separation, but their fabrication remains challenging. Here, we report for the first time the design and preparation of homochiral polycrystalline MOF-808 membranes for the first time. The membrane exhibits a high integrity and thin membrane thickness. Achieving homochirality through chiral amino acid postsynthetic modification, MOF-808 membranes demonstrate remarkable solvent stability. Notably, they successfully separated racemic naproxen enantiomers, achieving enantiomeric excess (ee) values of up to ∼95.0%. This work paves the way for turning achiral polycrystalline MOF membranes into high-performance chiral membranes for enantioselective separation.

Chiral gold nanorod vertical arrays for enantioselective chemiluminescence recognition of naproxen and mechanism revealing

Chirality recognition by monitoring electrochemiluminescence/chemiluminescence (CL) signals of probes altered by enantiomers is considered a promising method in the fields of pharmaceuticals and biotechnology. However, improving the sensitivity of chiral recognition and accurately elucidating its chiral recognition mechanism are still two major challenges. Herein, L-Cys-modified chiral Au nanorod (L-GNR) vertical arrays-enhanced CL sensing is proposed for improving the sensitivity of chiral naproxen recognition and accurately elucidating its chiral recognition mechanism. The resulting L-GNR vertical arrays exhibited a strong local electric field and improved electron transfer efficiency, thereby enhancing the CL signal of the luminol-H2O2 system. More importantly, such L-GNR vertical arrays exhibited markedly different CL intensities toward chiral drug R/S-naproxen (R/S-NPx) due to the different affinity between L-Cys and R/S-NPx, which was confirmed by molecular dynamics simulation. Thus, an ultrasensitive enantioselective recognition of R/S-NPx was achieved by the L-GNR vertical arrays exhibiting a CL signal for S-NPx that was approximately 2.5-fold higher than that of R-NPx, with a limit of detection as low as 0.14 pM for R-NPx and 0.097 pM for S-NPx, respectively. The mechanism of the stereospecific interaction between the naproxen enantiomers and the chiral GNR vertical arrays was investigated by scanning electrochemical microscopy (SECM). We found that the electron transfer rate of identification system determined strength of the CL signals. The electron transfer rate of L-GNR vertical arrays + R-NPx was faster than that of the L-GNR vertical arrays + S-NPx due to the weaker interaction between L-GNR vertical arrays and R-NPx compared to L-GNR vertical arrays and S-NPx. This study not only provides a novel strategy for the detection of enantiomers but also reveals the mechanism of enantioselective recognition through SECM.

Composite and Nanocomposite Thin-film Structures Based on Chitosan Succinamide

Aim: Currently, developing composite and nanocomposite materials based on natural polymers is attracting the growing attention of scientists. In particular, chitosan succinate, a modified biopolymer, has good biocompatibility, biodegradability, and electrical conductivity, allowing it to be used as a functional material for creating various electronic devices, including sensors for use in medicine and pharmaceuticals. Composite sensors based on chitosan derivatives have found application for the recognition and determination of enantiomers of tryptophan, tyrosine, naproxen, and propranolol in human urine and blood plasma in tablet forms of drugs without a preliminary active substance. Methods: This article discusses the studies on composite and nanocomposite thin-film structures based on chitosan succinamide obtained using various fillers, such as graphene oxide, singlewalled carbon nanotubes, and carbon adsorbents. Result: The studies used cyclic voltammetry, electrochemical impedance spectroscopy, and atomic force microscopy. The results created field-effect transistors based on the films in question as the transport layer. Conclusion: The mobility of charge carriers was estimated, and the following values were obtained: μ(SCTS) = 0.173cm2 /V·s; μ(SCTS-GO) = 0.509 cm2 /V·s; μ(SCTS-CP) = 0.269 cm2 /V·s; μ(SCTS-CB) = 0.351cm2 /V·s; μ(SCTS-SWCNT) = 0.713 cm2 /V·s.

Fabrication of a bifunctional fluorescent chiral composite based on magnetic Fe3O4/chiral carbon dots@hierarchical porous metal-organic framework

Considering the selective pharmacological activity and ecotoxicity of chiral drugs, the development of chiral materials with the dual functions of enantiomeric recognition and adsorption is of great significance. Herein, a novel bifunctional chiral composite (Fe3O4/CCDs@HP-ZIF-8) which does not contain expensive and rare fluorescent chiral ligands or metal ions, was constructed for the first time by encapsulating chiral carbon dots (CCDs) and magnetic Fe3O4 nanoparticles into hierarchical porous metal-organic frameworks (HP-MOFs). Fe3O4/CCDs@HP-ZIF-8, which integrates fluorescent chiral property, magnetism, and hierarchical porosity, shows enormous potential in enantiomeric recognition and adsorption. Fluorescence detection results demonstrate that Fe3O4/CCDs@HP-ZIF-8 presents different fluorescence quenching for naproxen enantiomers. The limits of detection are determined to be 0.05 μM for S-naproxen (S-Nap) and 0.30 μM for R-naproxen (R-Nap), respectively. Furthermore, the isothermal, kinetic, and thermodynamic adsorption behaviors of Fe3O4/CCDs@HP-ZIF-8 to naproxen enantiomers were systematically studied. Due to its hierarchical porosity, the composite exhibits higher adsorption capacity to naproxen enantiomers compared to the non-hierarchical porous composite. Studies of enantiomeric recognition and adsorption mechanisms affirm that the synergistic effect of multiple mechanisms exists between Fe3O4/CCDs@HP-ZIF-8 and naproxen enantiomers. Finally, the satisfactory recoveries and relative standard deviations in the actual sample assays demonstrate the practicality of Fe3O4/CCDs@HP-ZIF-8 for S-Nap detection. This non-destructive functionalization method creates an innovative pathway for developing advanced multifunctional chiral materials, holding great promise for enantiomeric recognition and adsorption.

A Voltammetric Sensor Based on Aluminophosphate Zeolite and a Composite of Betulinic Acid with a Chitosan Polyelectrolyte Complex for the Identification and Determination of Naproxen Enantiomers

A voltammetric sensor was developed based on a glassy carbon electrode with aluminophosphate zeolite finely dispersed on its surface, modified with a polyelectrolyte complex of chitosan with succinyl chitosan and betulinic acid, for the selective detection and determination of naproxen enantiomers. The electrochemical and analytical characteristics of the sensor were studied, and the effective electrode surface area (A = 9.8 ± 0.5 mm2) and charge transfer resistance (Ret = 649.9 ± 0.4 Ω) were calculated. In determining naproxen enantiomers, calibration characteristics are linear in the range from 2.5 × 10–5 to 1 × 10–3 M with limits of detection of 1.1 × 10–7 and 1.5 × 10–7 M and limits of quantification of 3.6 × 10–7 and 4.9 × 10–7 M for R- and S-naproxen, respectively. The sensor is more sensitive to R-naproxen (∆Ep = 60 mV, ipR/ipS = 1.40). The proposed sensor was used to recognize and determine naproxen enantiomers in human urine and plasma samples. Statistical evaluation of the results by the standard addition method showed that there was no systematic error.

A Voltammetric Sensor Based on Aluminophosphate Zeolite and a Composite of Betulinic Acid with a Chitosan Polyelectrolyte Complex for the Identification and Determination of Naproxen Enantiomers

A Voltammetric Sensor Based on Aluminophosphate Zeolite and a Composite of Betulinic Acid with a Chitosan Polyelectrolyte Complex for the Identification and Determination of Naproxen Enantiomers

Preparation and chromatographic performance of chiral peptide-based stationary phases for enantiomeric separation.

This study presents the development of three new chiral stationary phases. They are based on silica modified with peptides containing phenylalanine and proline. Successful analyses and characterizations were conducted using Fourier transform infrared spectra, elemental analysis, and thermogravimetric analysis. After this, the enantioselective performance of the three chiral peptide-based columns was evaluated. The evaluation used 11 racemic compounds under normal-phase high performance liquid chromatography mode. Optimized enantiomeric separation conditions were established. Under these conditions, the enantiomers of flurbiprofen and naproxen were successfully separated on CSP-1 column: the separation factor of these was 1.27 and 1.21, respectively. In addition, the reproducibility of the CSP-1 column was also investigated. The results of the investigation illustrated that the stationary phases have good reproducibility (RSD = 0.73%, n = 5).

Binaphthalene-based cyclic homochiral ureas and their structure-related properties

The direct connection of S-1,1′-binaphthalene with the urea moiety results in strained cyclic structures. Regardless of the conformational mobility, the 2+2 structure proved to be a chiral solvating agent for naproxen enantiomers.

Voltammetric chiral recognition of naproxen enantiomers by N-tosylproline functionalized chitosan and reduced graphene oxide based sensor

The chemical analysis of chiral compounds is of concern to researchers in the field of science and technology due to the various physiological and therapeutic properties of enantiomers. This experimental work provides novel sensor based on glassy carbon electrode (GCE) modified by N-tosylproline functionalized chitosan (TsPro-Cs) and reduced graphene oxide (rGO) for voltammetric recognition of naproxen (Nap) enantiomers. Each component of the modifying coating contributes to the improvement of the analytical and operational characteristics of sensor. The proposed sensor was characterized by fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Electrochemical recognition and quantification of Nap enantiomers were carried out using differential-pulse voltammetry (DPV). The oxidation peaks current ratio (IR/IS) of DPV measurements could be reached at 1.4 and peaks potential separation (ER–ES) of 40 mV. It was supposed that the chiral recognition occurred due to steric effect between N-tosylproline functionalized chitosan and Nap enantiomers. The binding energy of the chiral selector with the analyte molecule is higher for R-Nap than for S-Nap by 9.5 kcal/moll according to computational studies. The linear determination range was established as 20–500 μM for both enantiomers and detection limits of 0.4 μM and 0.9 μM were obtained for R- and S-Nap, respectively. The electrode showed good reproducibility with relative standard deviations of 1.8 % and 2.1 % for R- and S-Nap, respectively. The proposed sensor GCE/rGO-TsPro-Cs correctly determined Nap enantiomers in biological fluids with adequate precision and recovery ranged from 94 to 99 %. The developed sensor can determine the ratio of Nap isomers in enantiomeric mixture, which suggests that this sensor is an attractive candidate for practical use. This novel GCE/rGO-TsPro-Cs sensor can be a promising tool as an express device for monitoring the therapy of various diseases, as well as at the stage of drug production, and also for monitoring the impact of naproxen enantiomers on ecosystems and human health.

Synthesis and Characterization of a Glycine‐L‐Histidine‐Based Chiral Ionic Liquid and Enantioselectivity Evaluation by Fluorescence Spectroscopy

AbstractA chiral ionic liquid (CIL) derived from the dipeptide glycine‐L‐histidine (Gly‐L‐His) cation and bis(trifluoroethyl)sulfonyl imide (NTF2) anion was prepared. The CIL was synthesized via ion‐exchange and evaluated for purity, melting points, thermal stability, and chiral recognition ability. The thermal decomposition temperature of [Gly‐L‐His][NTF2] CIL was 356 °C. The melting point of the CIL was ∼100 °C. The CIL was found to have a fluorescence emission peak with a λmax at 440 nm upon excitation at 364 nm. Fluorescence spectroscopy studies showed that the CIL exhibited chiral recognition ability for enantiomers of naproxen, propranolol, and 2,2,2‐trifluoroanthryl ethanol. The glycine‐L‐histidine bis(trifluoroethyl) sulfonyl imide IL effectively served as a solvent and chiral selector. The high thermal stability of this CIL indicates potential to be used as a solvent and chiral selector in high temperature reactions and as a stationary phase for gas chromatography.

Chiral Covalent Organic Framework Packed Nanochannel Membrane for Enantioseparation

AbstractA nanochannel membrane has the prospect of large‐scale separation. However, selectivity in enantioseparation is a challenge, due to the size difference between nanochannels and enantiomers. Here, we compartmented nanochannels by the in situ synthesis of a L‐tyrosine functionalized covalent organic framework (L‐Tyr‐COF). The L‐Tyr‐COF decreased the pore size of channels to match with naproxen enantiomers (S/R‐NPX) and improved the enantioselective gating. In contrast to the surface‐functionalized nanochannels (L‐Tyr channel), the L‐Tyr‐COF packed nanochannels (L‐Tyr‐COF channel) exhibited high enantioselectivity for S‐NPX and realized the enantioseparation with the enantiomer excess value up to 94.2 %. The separation flux through the highly porous L‐Tyr‐COF channel was 1.33 mmol m−2 h−1. This study provided a size‐matching strategy and the chiral covalent organic framework packed nanochannel membrane to realize enantioseparation with high selectivity and flux.

Chiral Covalent Organic Framework Packed Nanochannel Membrane for Enantioseparation

A nanochannel membrane has the prospect of large-scale separation. However, selectivity in enantioseparation is a challenge, due to the size difference between nanochannels and enantiomers. Here, we compartmented nanochannels by the in situ synthesis of a L-tyrosine functionalized covalent organic framework (L-Tyr-COF). The L-Tyr-COF decreased the pore size of channels to match with naproxen enantiomers (S/R-NPX) and improved the enantioselective gating. In contrast to the surface-functionalized nanochannels (L-Tyr channel), the L-Tyr-COF packed nanochannels (L-Tyr-COF channel) exhibited high enantioselectivity for S-NPX and realized the enantioseparation with the enantiomer excess value up to 94.2 %. The separation flux through the highly porous L-Tyr-COF channel was 1.33 mmol m-2 h-1 . This study provided a size-matching strategy and the chiral covalent organic framework packed nanochannel membrane to realize enantioseparation with high selectivity and flux.

From the Periodic Properties of Metals to the Rietveld Refinement of the Pharmaceutical Molecule Naproxen: Three Remote Experiments about X-ray Diffraction

Recently there is an increasing need for experiments that can be conducted remotely. In this sense, this paper presents three experiments about materials science and an X-ray diffraction (XRD) technique that can be taught and performed entirely remotely. The first experiment is about the calculation of lattice parameters, atomic radii, and densities of metallic elements with a body-centered cubic (BCC) structure. The second experiment is about the calculation of lattice parameters, axial ratios, unit cell volumes, and densities of yttria-stabilized zirconia (YSZ) solid solutions. The third experiment is about applying the Rietveld refinement technique to distinguish the enantiomers of the pharmaceutical molecule naproxen and determine the hydration degree of commercial naproxen sodium pills. For the first two experiments, students worked with simulated data, whereas for the third one, they worked with experimental data collected and provided by the Instructor. Besides the materials science and XRD concepts, students were introduced to the operation of the free softwares Vesta and GSAS II and to the Crystallography Open Database, a free database for structural data of organic and inorganic compounds. The paper explains the background, goals, and results obtained by the students in each one of the experiments. Detailed information about the experimental procedures and their implementation is complemented by the Supporting Information file and Supporting Videos. Although the experiments were presented in an increasing level of difficulty, they are independent of each other, allowing the instructors to apply them according to their needs and learning objectives.

Enantioselective Antiport in Asymmetric Nanochannels.

Enantioselective sensing and separation are major challenges. Nanochannel technologies are energy-saving and efficient for membrane separation. Herein, inspired by biological antiporter proteins, artificial nanochannels with antiporter behavior were fabricated for chiral sensing and separation. Tyrosine enantiomers were incorporated into hourglass-shaped nanochannels via stepwise modifications to fabricating multiligand-modified asymmetric channels. Chiral distinction of naproxen enantiomers was amplified in the l-Tyr/d-Tyr channels, with an enantioselectivity coefficient of 524, which was over 100-fold that of one-ligand-modified nanochannels. Furthermore, transport experiments evidenced the spontaneous antiport of naproxen enantiomers in the l-Tyr/d-Tyr channels. The racemic naproxen sample was separated via the chiral antiport process, with an enantiomeric excess of 71.2%. Further analysis using electro-osmotic flow experiments and finite-element simulations confirmed that the asymmetric modified multiligand was key to achieving separation of the naproxen enantiomers. We expect these multiligand-modified asymmetric nanochannels to provide insight into mimicking biological antiporter systems and offer an approach to energy-efficient and robust enantiomer separation.

Enantioseparation on a new synthetic β-cyclodextrin chemically bonded chiral stationary phase and molecular docking study.

A novel β-cyclodextrin derivative chemically bonded chiral stationary phase (EDACD) was synthesized by the reaction of mono-6-ethylenediamine-β-cyclodextrin with the active alkyl isocyanate, anchoring to silica gel. After the successful analysis and characterization using scanning electron microscopy, Fourier transform infrared spectra, solid-state nuclear magnetic resonance spectra, elemental analysis, and thermogravimetric analysis techniques, the enantioselective performance of the as-prepared EDACD column was evaluated by non-steroidal antiinflammatory drugs and flavonoids under the reversed-phase HPLC condition. The factors that affected enantioseparation including mobile phase compositions and buffers were investigated in more detail. As a result, EDACD showed a satisfactory enantioselectivity for the tested drugs. With the mobile phase of acetonitrile and 20-mM ammonium formate adjusted to pH4.0 using formic acid (85:15, v/v) at the flow rate of 0.6mLmin-1, the enantiomers of ibuprofen, carprofen, naproxen, indoprofen, ketoprofen, eriocitrin, naringin, and narirutin were separated with the best resolutions of 1.53, 1.64, 3.72, 2.40, 0.50, 0.61, 0.58, and 0.52. To adjust the proportion of acetonitrile to 80% (by volume), the enantiomers of pranoprofen and flurbiprofen were completely resolved with the best resolutions of 1.60 and 1.59. Additionally, by the study of the molecular docking, hydrogen bonding and inclusion complexation were believed to play an important role in chiral recognition. As a new material, EDACD will have a wider application in the analysis of chiral compounds.

Hydroxypropyl-β-cyclodextrin encapsulated stationary phase based on silica monolith particles for enantioseparation in liquid chromatography.

Hydroxypropyl-β-cyclodextrin-encapsulated stationary phase incorporated on silica monolith particles was prepared by physical embedding, providing a new method for the development of chiral stationary phase for enantioseparation in liquid chromatography. Ground silica monolith particles of about 2.0μm were prepared via sol-gel reaction followed by differential sedimentation. Initially, the silica monolith particles were pretreated with 3-trimethoxysilyl propyl methacrylate to attach double-bonded ligands onto the surface, then a network structure was formed onto the surface of the particle using N-isopropyl acrylamide as functional monomer. Hydroxypropyl-β-cyclodextrin was encapsulated inside N-isopropyl acrylamide copolymerized layer on the surface of silica monolith particles. The effect of the amount of chiral selector on the chromatographic efficiency of the chiral stationary phase was examined. The glass lined stainless steel columns (1mm internal diameter, 300mm length) were packed with the stationary phase for estimation of the efficiency by separation of phenylsuccinic acid, oxybutynin, equol, and naproxen enantiomers in high-performance liquid chromatography, with the resolutions of 1.54, 1.72, 2.54, and 2.31, respectively. The column to column repeatabilities through relative standard deviation were found better than 3%. The experimental results indicate that the sol-gel ground silica particles modified with β-cyclodextrin provide a promising way for the separation of chiral enantiomers.

Carbon quantum dots embedded silica molecular imprinted polymer as a novel and sensitive fluorescent nanoprobe for reproducible enantioselective quantification of naproxen enantiomers

The nanoparticles of carbon quantum dots embedded silica molecular imprinted polymer (CQDs-SiO2@MIP) were utilized as novel, sensitive, repeatable, and reproducible enantioselective fluorescent nanoprobes for enantioselective quantification of naproxen molecules. The combination of MIP and CQDs was the basis for selectivity enhancement in chiral recognition of naproxen enantiomers due to template selectivity of the synthesized CQDs-SiO2@MIP. Introducing naproxen molecules to the system, selectively induced a considerable quenching of the fluorescence of the CQDs-SiO2@MIP with an efficient distinction between S- and R-enantiomers. The method showed a wide linear working range of 0.5–35.0 µM for S-naproxen and 0.5–30.0 µM for R-naproxen. However, the calibration sensitivity for S-naproxen was estimated at 2.0-fold higher than R-naproxen. Also, the detection limits were calculated to be 0.20 and 0.37 µM for S- and R-naproxen, respectively. The relative standard deviations (RSD %) as an index for repeatability and reproducibility of the developed method were estimated to be 1.4% and 4.0% for intra-day and inter-day assays, respectively.

Chiral molecularly imprinted polymeric stir bar sorptive extraction for naproxen enantiomer detection in PPCPs

Chiral micropollutant analysis in pharmaceuticals and personal care products (PPCPs) is interesting but challenging. We firstly developed a series of chiral molecularly imprinted polymeric (CMIP) stir bar sorptive extraction coatings by combining a chiral template with chiral functional monomers via a click reaction for naproxen enantiomer analysis in PPCPs. Heterochiral selectivity was observed in the molecule recognition of the CMIP coatings, which demonstrated good adsorption capability for the chiral template and its structurally similar chiral compounds. The coatings also exhibited excellent enrichment capability for chiral analytes in an aqueous matrix. The surface morphology and pore structure of the CMIP coatings were characterized. The molecular interactions between the chiral template and chiral functional monomer were investigated through UV–vis spectroscopy and theoretical calculations to prove the effective interactions existing in the heterochiral MIPs. The CMIP coatings were used to enrich naproxen enantiomers in chiral drug and environmental water samples, and satisfactory recoveries (83.98 %–118.88 %) with a relative standard deviation of 3.49 %–13.08 % were achieved. The heterochiral imprinted coating-based method provided a sensitive, selective, and effective enrichment strategy for chiral micropollutant analysis in PPCPs. This technique is critical for chiral molecule recognition and enantiomer analysis in complex samples.

Enantiomeric separation and enantioselective determination of some representive non-steroidal anti-inflammatory drug enantiomers in fish tissues by using chiral liquid chromatography coupled with tandem mass spectrometry

In this work, enantiomeric separation of nine non-steroidal anti-inflammatory drugs including ibuprofen, indoprofen, pranoprofen, flurbiprofen, ketoprofen, carprofen, naproxen, loxoprofen and etodolac was investigated by HPLC combining with four polysaccharide based chiral stationary phases (Chiralpak IA, Chiralpak IB, Chiralpak IC and Chiralpak ID). The effect of various types of the mobile phase, acidic additive types, as well as mobile phase pH on enantiomeric separation was evaluated and optimized in detail. Chiralpak ID showed the best enantioselectivity towards seven of the above nine chiral drugs. Additionally, a sensitive and simple method for simultaneous enantioselective determination of indoprofen, flurbiprofen, carprofen and naproxen enantiomers in fish tissues based on C18 solid phase extraction (SPE) with chiral liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) on Chiralpak ID was established. Method validation showed that good linearity (R2 > 0.99) for each enantiomer with the limit of quantification in the range of 2–10 ng g−1 was obtained. Recoveries of the studied profens enantiomers in fish tissues were 82.6% - 106.7% with RSD less than 8.2% at three concentration levels. The proposed method was applied to the real fish samples analysis, providing a reference to fully evaluate the risks of these drug enantiomers in food or environmental samples.