Racemic Tryptophan Research Articles

Preparation and application of a chiral Am7CD-modified COF composite membrane by interfacial polymerization

Membrane separation technology has infinite potential to produce optically pure drugs. However, there are still challenges regarding chiral membranes, such as the single separation object, poor mechanical properties, and constrained relationship between permeability and enantioselectivity. To improve the membrane properties, heptakis (6-amino-6-deoxy)-β-CD-modified carboxyl-functionalized COF (TpBD-Am7CD) was introduced as a chiral functional material for the preparation of a TpBD-Am7CD stainless steel I-Net cellulose acetate membrane (COF/SSCAM) via interfacial polymerization. Using tryptophan as the template molecule, the membrane preparation and filtration conditions were optimized to achieve maximum enantioselectivity. The optimized COF/SSCAM achieved a better enantiomeric excess percentage (e.e.% = 100.00%) and solute permeation flux (JS = 37 × 10−6 mol m−2 h−1) for racemic tryptophan than the support membrane, which was attributed to the enantioselectivity and hydrophilicity of TpBD-Am7CD. Moreover, COF/SSCAM achieved enantiomeric separation of racemates of propranolol, warfarin, atenolol, and metoprolol, and the e.e.% values were 39.51%, 5.60%, 16.04%, and 3.09%, respectively. In addition, the chiral recognition mechanism was investigated by molecular docking simulation.

Improvement of the enantioselectivity of lipase catalyzed reactions with deoxycholic acid‐based molecular tweezers

AbstractBACKGROUNDLipase as a hydrolase has important applications in the synthesis of chiral drugs. Based on the special interfacial activity of lipase, bile salt as a biosurfactant can effectively improve the catalytic activity of lipase.RESULTSIn this work, the strong selective recognition of the molecular tweezers and guest molecules helps improve the guest molecule concentration near the lipase catalytic center. However, this strong recognition will also make it difficult for the guest molecules to break away from the molecular tweezers. Therefore, there is an optimal value for this recognition that can effectively improve the chiral resolution effect of lipase.CONCLUSIONSThe two hydroxyl groups on deoxycholic acid were modified to prepare deoxycholic acid‐based molecular tweezers with two ‘arms’ and one ‘crack.’ The recognition performance between the molecular tweezers and amino acid methyl ester was determined by UV spectrophotometry. According to the binding constant, Ka, and free energy, −ΔG0, a complex formed between the deoxycholic acid‐based molecular tweezers (host) and amino acid methyl ester (guest) due to chiral recognition. Molecular tweezers were subsequently mixed with porcine pancreatic lipase (PPL) and candida rugosa lipase (CRL), respectively, to catalyze the transesterification of racemic tryptophan methyl ester. © 2023 Society of Chemical Industry.

Unlocking the potential of Escherichia coli modified magnetic particles for chiral discrimination of racemic tryptophan

Enzymes possess a highly specific affinity toward their substrates. In this study, an enzyme-based biological method was established for chiral discrimination of D/L-tryptophan (Trp). The polydopamine modified magnetic particles (PDA@Fe3O4) were prepared for immobilization of the genetically engineered bacterium Escherichia coli (E. coli) DH5α. The bacteria-magnetic particles conjugates (bacteria@PDA@Fe3O4) demonstrate excellent chiral discrimination performance toward D/L-Trp at pH 7.0 and 45 °C. The investigation for the principle exhibits that the immobilized E. coli DH5α can produce tryptophanase, and the enzyme can selectively recognize and degrade L-Trp. The Michaelis constant of tryptophanase produced by bacteria@PDA@Fe3O4 was measured to be 25.7 µg mL−1. This method avoids the purification of tryptophanase and unlocks the potential of bacteria modified magnetic particles for chiral discrimination of racemic tryptophan.

Molecularly imprinted polymer functionalized silica nanoparticles for enantioseparation of racemic tryptophan in aqueous solution.

A method has beendeveloped for preparation of surface molecularly imprinted polymer functionalized silica nanoparticles (SiO2@MPS@MIP). Firstly, the silica nanoparticles are prepared by a one-pot sol-gel method using tetraethylorthosilicate and 3-methacryloxypropyltrimethoxysilane as functional monomers. Next, the template molecule (L-Trp) is self-assembled with the functional monomer (acrylamide). Finally, SiO2@MPS@MIP are prepared using N,N'-methylenebisacrylamide as the cross-linker. The prepared SiO2@MPS@MIP have an average diameter of about 6.3 ± 1.2nm. They exhibit good selectivity toward L-Trp with an imprinting factor of 6.3. The adsorption isotherm data was well described by the Langmuir model. The maximum adsorption capacities of SiO2@MPS@MIP for L-Trp and D-Trp were calculated to be 11.1 ± 0.9 and 2.66 ± 0.16mgg-1, respectively. An enantiomer excess value of 100% was achieved after adsorption of racemic Trp by the material. The work suggests that SiO2@MPS@MIP are a promising material for enantioseparation of Trp racemate in aqueous media. Graphical abstract.

The investigation of the reversed enantio-selectivity by an alpha-cyclodextrin doped thin film composite membrane

A facilitated-transport enantio-separation mechanism was proposed in this study and verified with an enantio-selective thin film composite membrane. The polysulfone membrane substrate was first fabricated at the optimized conditions, and the chiral selector α-CD was then incorporated into the selective layer by mixing with the MPD monomer for interfacial polymerization. Racemic tryptophan was employed as the model selectant, and inversed enantio-selectivities, 1.55 and 0.6 were observed from two different operation mode driven by concentration gradient and pressure gradient, respectively. The facilitated-transport separation mechanism was demonstrated by the concentration driven mode. The effects of other influencing factors including racemic feed concentration, α-CD concentration and pressure were also investigated.

Synthesis of molecularly imprinted polymer modified magnetic particles for chiral separation of tryptophan enantiomers in aqueous medium

Molecularly imprinted polymers coated magnetic particles (Fe3O4@MIPs) were prepared and used as adsorbents in solid phase extraction for efficient enantioseparation of racemic tryptophan (Trp) in aqueous medium. The amino-modified magnetic particles (Fe3O4-NH2) were first synthesized by one-pot hydrothermal method. Then the template molecules (L-Trp) were assembled on the surface of Fe3O4-NH2. Finally, Fe3O4@MIPs were prepared via a sol-gel method using L-Trp@Fe3O4-NH2 complex as matrix, 3-aminopropyltriethoxylsilane and n-octyltriethoxysilane as functional monomers. The as-prepared Fe3O4@MIPs were spherical with an average diameter about 149 ± 6.0 nm. The thickness of MIPs layer was approximately 3.5 ± 2.3 nm. The adsorption isotherms data of Fe3O4@MIPs toward L-Trp and D-Trp were well described by the Langmuir model. The maximum adsorption capacities of Fe3O4@MIPs for L-Trp and D-Trp were calculated to be 17.2 ± 0.34 mg/g and 7.2 ± 0.19 mg/g, respectively. The material exhibited good selectivity toward L-Trp with imprinting factor of 5.6. Excitingly, the enantiomeric excess (ee) of Trp in supernatant after adsorption of racemic Trp by Fe3O4@MIPs was as high as 100%. The result suggests that the imprinted caves in Fe3O4@MIPs are highly matched with L-Trp molecule in space structure and spatial arrangement of active functional groups. The work also demonstrates that sol-gel technology has great potential in preparation of MIPs for chiral separation.

Preparation of PSEBS membranes bearing (S)-(−)-methylbenzylamine as chiral selector

Nowadays, there is a strong need for replacement of racemates by enantiomerically pure drugs. Enantioseparation on polymer membranes seems to be one of the promising and economically feasible technologies for this purpose. As a material for membrane construction, linear polymer molecules bearing covalently bonded chiral selectors are very promising according to recent reports. A membrane formed from chloromethylated polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (PSEBS) was cast and subsequently functionalized with a chiral selector (S)-(−)-α-methylbenzylamine. In preferential sorption experiments with racemic tryptophan and ibuprofen, the prepared membrane exhibited a higher affinity to l-tryptophan and (R)-(−)-ibuprofen than to corresponding enantiomers. The significant change in peak ratio from 48:52 to 60:40 (d-tryptophan:l-tryptophan) was observed. This indicates the high potential of the covalently bonded (S)-(−)-α-methylbenzylamine selector for the fabrication of membranes selective towards chiral acids and ampholytes.

Enantioselective Separation of Racemic Tryptophan with Sonochemically Prepared Egg Albumin Microspheres

AbstractNew approaches for chiral resolution are gaining importance and are of economic interest for the development of pharmaceuticals, agrochemicals, chiral sensors and food additives. Herein we disclose the first examples in which sonochemically prepared egg albumin microspheres (EAMs) were used for chiral resolution of an amino acid. When EAMs were in contact with an aqueous solution of racemic tryptophan (Trp) they selectively interacted with L‐Trp leading to 94% enantiomeric excess (ee) of D‐Trp. In a control experiment in which the egg protein, without applying ultrasonic waves to form microspheres, was dissolved and exposed to racemic Trp, no chiral resolution was observed. The effects of temperature and concentration were studied in detail. These preliminary results show that EAMs produced by sonication may provide a simple, cost‐effective an unconventional way to chiral separation of racemic amino acids.

Preparation and Characterization of Cellulose Membrane Modified with β-Cyclodextrin for Chiral Separation

In this study, it is first time to obtain a complete separation of using β-cyclodextrin (β-CD) modified cellulose microfiltration membrane. Commercially cellulose membrane with the pore diameter of 0.22μm was functionalized with β-cyclodextrin (β-CD) by aldolization at the solid–liquid interface. Filtration experiments were carried out using a dead-end filtration cell holding a flat sheet membrane with effective area of 36 mm2. Aqueous solution of racemic tryptophan (0.05g/L, 150 mL) was forced to permeate through the cellulose membrane immobilized by β-CD at a flow rate of 0.1 ml/min through the membrane microdevice. Chiral ligand exchange chromatography was used to determine the concentration and ratio of D- and L-tryptophan in the filtrate. A complete separation of racemic tryptophan can be obtained by using this novel composite membrane-based separation system. In addition, a multi-stage filtration separation was applied in order to obtain higher permselectivity. The objective of this study is to obtain an easy prepared chiral membrane with good reproducibility and can be applied to a variety of chiral separations.

Green preparation and selective permeation of d-Tryptophan imprinted composite membrane for racemic tryptophan

Enantioseparation of racemic tryptophan is very important for pharmaceutical production. Conventional separation methods are high costly, energy intensive and environmentally unfriendly. Permeation separation based on membrane separation technique is a promising technology with advantages of energy efficient, clean and no additives. However, lots of organic compounds are commonly used for the traditional preparation of various membranes for enantioseparation of racemic tryptophan. Thus, we developed a totally green and clean preparation method using nature polymer sodium alginate as functional polymer, water as solvent and CaCl2 as crosslinking agent. Besides, polyvinylidene fluoride membrane was selected as supported membrane. Molecularly imprinted technology with d-Tryptophan as template molecule was introduced to enlarge mass transfer flux. Various methods were used in characterization of molecularly imprinted composite membrane (MICM) and non-imprinted composite membrane (NICM). Effects of preparing conditions, permeation conditions and concentration polarization on permeation performance of MICM by pressure-driven were investigated. High enantiomeric excess (ee%>98%) of the permeation solution could be obtained under mild conditions. Reducing the presence of concentration polarization was beneficial to maintaining high ee% (>98%). Moreover, the thermo and chemical stability of MICM were studied too. Comparison with previous studies indicated that the proposed totally green and clean method was not only low costly and environment friendly but also beneficial to significantly increasing ee.

Green preparation of d-tryptophan imprinted self-supported membrane for ultrahigh enantioseparation of racemic tryptophan

Green and clean preparation of molecularly imprinted membrane for ultrahigh enantioseparation of racemic tryptophan.

ChemInform Abstract: Convenient Synthesis of 1‐Aryl‐9H‐β‐carboline‐3‐carbaldehydes and Their Transformation into Dihydropyrimidinone Derivatives by Biginelli Reaction.

Abstract In the present work, a practical synthesis of 1-aryl-β-carboline-3-carbaldehydes as versatile building blocks and their application in Biginelli reaction is reported. The starting material of the four-step synthesis is racemic tryptophan methyl ester. The procedure involves a Pictet–Spengler cyclization, a dehydrogenation, an ester reduction, and an alcohol oxidation step. The β-carboline-3-carbaldehydes were further transformed using a Biginelli reaction into derivatives containing a pharmacologically significant dihydropyrimidine ring at position-3.

Convenient synthesis of 1-aryl-9H-β-carboline-3-carbaldehydes and their transformation into dihydropyrimidinone derivatives by Biginelli reaction

In the present work, a practical synthesis of 1-aryl-β-carboline-3-carbaldehydes as versatile building blocks and their application in Biginelli reaction is reported. The starting material of the four-step synthesis is racemic tryptophan methyl ester. The procedure involves a Pictet–Spengler cyclization, a dehydrogenation, an ester reduction, and an alcohol oxidation step. The β-carboline-3-carbaldehydes were further transformed using a Biginelli reaction into derivatives containing a pharmacologically significant dihydropyrimidine ring at position-3.

Enantioseparation of Racemic Mixtures Based on Solvent Sublation

A method of solvent sublation was developed for the enantioseparation of racemic ofloxacin (rac Oflx) and racemic tryptophan (rac Trp). In this method, dibenzoyl-L-tartaric acid (L-DBTA) and di-(2-ethylhexyl) phosphoric acid (D2EHPA) and sodium lauryl sulfate (SDS) were used as chiral coextractants and foamer, respectively. Several important parameters influencing the separation performances, such as pH in aqueous phase, concentrations of rac mixtures, L-DBTA, D2EHPA, and SDS, were investigated. Under the optimal operation conditions, the enantiomeric excess and enantioselectivity were 60.08% and 5.58 for Oflx and 65.09% and 6.31 for Trp, respectively. The yields of D-enantiomer and L-enantiomer were 34.23% and 8.54% for Oflx and 18.59% and 3.93% for Trp, respectively. The results suggest that the enantioselectivities have been enhanced compared with the traditional chiral extraction. This technique is an efficient chiral separation method, with many advantages such as low expenditures of organic solvent, low consumption of chiral extractant, and easy realization of multistage operation.

Preparation, characterization and application of β-cyclodextrin-glutaraldehyde crosslinked membrane for the enantiomeric separation of amino acids

The polysulfone membrane (PS) and β-cyclodextrin glutaraldehyde crosslinked polysulfone membrane (β-CDXM) were prepared by phase inversion technique from the solutions prepared by solubilizing polysulfone polymer, β-cyclodextrin in N, N-dimethyl formamide (DMF) and adding glutaraldehyde. The membranes were extensively characterized by various techniques including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM) and atomic force microscopy (AFM) to correlate membrane characteristics with their performance. ATR-FTIR and XRD studies indicated strong hydrogen bonding interactions between polysulfone and glutaraldehyde crosslinked (XβCD) network. TGA indicates a different range of thermal degradation due to change in enthalpy and presence of crosslinked structure. The membranes were tested by performing separation of enantiomers from racemic phenylalanine (Phe) and racemic tryptophan (Trp) in reverse osmosis. The results of experiments indicated that incorporation of β-cyclodextrin in polysulfone polymer had provided enantiomer discriminating capability to the membrane therefore β-CDXM had exhibited enantioselectivity for D-Phe and D-Trp. The observation confirmed that chiral environment is essential for enantiomer separation. The maximum enantioselectivity (>81%) was observed for the D-Phe.

Synthesis and application of clindamycin succinate as a novel chiral selector for capillary electrophoresis

A novel chiral selector, clindamycin succinate, was synthesized and first used as a chiral selector in capillary electrophoresis (CE). The chiral resolution ability of this kind of clindamycin derivation was studied by CE using some racemic drugs as model analytes. From the experimental results, it was found that both resolution and selectivity of the selector were dependent on the following parameters: concentration of chiral selectors, pH of the running buffer, temperature of the capillary column, applied voltage and organic modifier used. The results show that the chiral selector possesses high resolution toward some racemic drugs, including ofloxacin, chlorphenamine, tryptophan, propranolol, sotalol and metoprolol. Excellent chiral resolution of these tested drugs was achieved under the optimal conditions of 50 mM clindamycin succinate, 10% MeOH v/v, 50 mM Tris buffer, pH 4.0, at 22 kV and 20 °C within 25 min.

Novel membrane processes for the enantiomeric resolution of tryptophan by selective permeation enhancements

AbstractNovel membrane processes for the effective enantioresolution of racemic mixtures have been evaluated. The incorporation of human serum albumin (HSA) in the strip solution of a permeation cell resulted in the partial optical resolution of a racemic tryptophan mixture, as the permeation of L‐tryptophan, which binds to HSA more strongly, was enhanced selectively over that of D‐tryptophan. A second approach in which a racemic mixture was introduced to the strip solution prior to the experiments showed better performance by selectively decreasing the flux of the more weakly bound D‐tryptophan. The highest enantioselectivity of ∼9.76 was achieved with a third, novel design consisting of two permeation cells in series, which can encompass the advantages of affinity dialysis. An industrial scale unit is proposed based on this concept and a suitably validated mathematical model. © 2010 American Institute of Chemical Engineers AIChE J, 2011

Comparative Study of Enantioseparation of Racemic Tryptophan by Ultrafiltration Using BSA-Immobilized and BSA-Interpenetrating Network Polysulfone Membranes

Effectiveness of Bovine Serum Albumin (BSA) as chiral recognizing protein in enantiomers separation by ultrafiltration technique was studied by immobilizing BSA on the membrane and incorporating BSA as semi-interpenetrating network in the membrane matrix. Separation of racemic tryptophan solution was performed in closed loop cross flow ultrafiltration using BSA immobilized polysulfone membrane and polysulfone membrane having BSA semi-IPN network. The volumetric flux (Jv), the solute flux (Js), the separation factor (α), and the enantiomeric excess (%ee) of two types of membranes at different trans-membrane pressures and permeation times were determined. BSA semi-IPN membrane exhibits higher volumetric as well as solute fluxes compared to BSA immobilized membrane. Separation factor (α) to the order of 1.89 was achieved with BSA immobilized membrane after 8 h of ultrafiltration and in the same duration BSA-IPN membrane exhibited separation factor (α) to the order of 1.62. BSA immobilized membrane exhibits higher enantiomeric excess (30.8%) compared to BSA semi-IPN membrane (23.8%) after 8 hrs. BSA molecules available on membrane as immobilized or as semi-IPN under go complexion with tryptophan enantiomers differently. BSA immobilized membrane performed better separation and enantiomeric purity; however, the solute flux of the membrane decreases.

The facile synthesis of an aldehyde-containing graft copolymer membrane for covalent protein capture with retention of protein functionality

The immobilization of biomolecules onto an insoluble carrier surface has always been a subject of great interest to enhance their resistance to pH and temperature, which aids in an increased activity lifespan as well as easy reuse of the said biomolecules. However, traditional methods are only able to provide single-layer biomolecular binding and require multiple chemical reactions to prepare the final substrate before the immobilization can be carried out properly. Here we report a facile one-step chemical synthesis of a new aldehyde-bearing graft copolymer via atom transfer radical polymerization (ATRP) for covalent protein capture in a multilayered approach to covalently capture bovine serum albumin (BSA) onto a polymeric membrane. The resultant protein-bound membrane illustrated the retention of BSA's stereoselective discrimination ability by binding to an excess of 2 mol of tryptophan/mol of BSA and demonstrated an enantioresolution of a 0.184 mM racemic tryptophan mixture with a time-averaged-separation factor of 2.9.

Effects of spacer arm length and benzoation on enantioseparation performance of β-cyclodextrin functionalized cellulose membranes

Abstract The enantiomeric resolution performance of cellulose membranes functionalized with chiral layers of beta-cyclodextrin (β-CD) of various spacer arm lengths has been investigated. 6-O-(p-toluenesulfonyl)-β-cyclodextrin (Ts-β-CD) was reacted with ethylenediamine (EDA), diaminopropane (PDA) and diaminobutane (BDA) to synthesize the aminated beta-cyclodextrins EDA-β-CD, PDA-β-CD and BDA-β-CD, respectively, which were subsequently grafted onto partially oxidized cellulose membranes via reductive amination. The enantioselectivity, in racemic tryptophan resolution, increased with decreasing spacer arm length, i.e., α BDA-β-CD α PDA-β-CD α EDA-β-CD , while the highest selectivity of 1.20 was obtained when a mixture of chiral selectors was grafted to the membranes. The lower selectivity of membranes grafted with longer spacer arms was attributed to their lower grafting efficiency and, consequently, the presence of more defective regions. Further improvement of enantioselectivity, to ∼1.3–1.5, was realized by substituting the hydroxyl groups on the aminated cyclodextrins with benzoate groups. This increase in enantioselectivity was consistent with molecular modeling predictions of the complex formation energies between the enantiomers and various chiral selectors.