Enantiomeric analysis of chiral phenyl aromatic compounds by coated capillary electrochromatography based on a MOF-on-MOF stationary phase.

Chiral phenyl aromatic compounds (CPACs) are widely used in drug development, food/cosmetic production, and other organic synthesis processes, and their different enantiomers have distinct physiological activities and application differences. A double-layer metal-organic framework composite (MOF-on-MOF) was obtained by in situ synthesis of chiral metal-organic framework (CMOM-3S) on the surface of an iron-based metal-organic framework (NH2-MIL-101(Fe)). According to our investigation, MOF-on-MOF composite was for the first time applied to the stationary phase of capillary electrochromatography (CEC), and enantioseparations of eight CPACs were accomplished. Compared with single CMOM-3S, the enantioseparation performance of the coated capillary columns based on NH2-MIL-101(Fe)@CMOM-3S was improved by 34.07 ~ 720.0%. The R-/S-mandelic acid in actual sample (apricot leaves) was detected by the newly CEC system to be 0.0118 mg mL-1 and 0.0523 mg mL-1, respectively. The spike recoveries were 96.60 ~ 104.7%, indicating its good stability and accuracy. In addition, the selective adsorption capacity of MOF-on-MOF composites was verified by adsorption experiments.

Dual-ligand 3D lammelar chiral metal-organic framework for capillary electrochromatographic enantioseparations.

Dual-ligand metal-organic frameworks (MOFs) based on tryptophan and camphoric acid were designed and synthesized as the stationary phase of the capillary electrochromatography (CEC) system. This CEC system showed significantly improved enantioseparation ability for nine drugs, compared with the single-ligand MOF stationary phase. Characterization methods such as N2 adsorption-desorption isotherms and scanning electron microscopy proved that the dual-ligand MOFs possessed excellent 3D spatial structures (ligand ratio is 1:1) which ensured the enantioseparation capability of the CEC system. The influence of ligand types on the chiral selectivity of MOFs was explored using racemic phenylalaninol and its single enantiomers as models. When the chiral type of the ligands is consistent, the enantioseparation ability of the CEC system is better. The chromatographic conditions such as buffer concentration, buffer pH, organic solvent addition ratio, and applied voltage were optimized, and satisfactory repeatability and stability of the CEC system were verified. Additionally, the enantioseparation mechanism of the CEC system was discussed through adsorption kinetic experiments, adsorption isotherm fitting, and thermodynamics.

One-step synthesis of chiral molecularly imprinted polymer TiO2 nanoparticles for enantioseparation of phenylalanine in coated capillary electrochromatography.

A novel chiral molecularly imprinted polymer TiO2 nanoparticle was synthesized in one step for the enantioseparation of phenylalanine in coated capillary electrochromatography. To the author's knowledge, the chiral molecularly imprinted nanomaterials have still not been reported, to date. Chiral molecularly imprinted TiO2 nanomaterials (L-PHE@MIP(APTES-TEOS)@TiO2) were used as a chiral stationary phase to separate the phenylalanine enantiomers in coated capillary electrochromatography (CEC). The imprinted coating was prepared from L-phenylalanine (L-PHE) as the template, TiO2 nanoparticles (NPs) as the support substrate, 3-aminopropyltriethoxysilane (APTES) as the functional monomer, and tetraethyl silicate (TEOS) as the cross-linker. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO2@capillary. Fourier transform infrared spectra (FT-IR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA) were employed for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO2. The effects of the applied voltage, pH value, buffer concentration, and acetonitrile content were investigated  experimentally to determine the optimum conditions for CEC. The best resolution for  phenylalanine enantiomers by CEC reached a value of 3.48. In addition, the specific recognition effect of L-PHE@MIP(APTES-TEOS)@TiO2 on PHE enantiomers was studied by selective experiment. Finally, adsorption kinetic research, adsorption equilibrium isotherm study, and adsorption thermodynamic experiment were carried out to investigate the separation mechanism of PHE enantiomers with the L-PHE@MIP (APTES-TEOS)@TiO2@capillary, and the results were consistent with those of CEC experiments.

Carboxymethyl-ß-cyclodextrin and histidine-zeolitic imidazolate framework-8 used for enantioseparation of three basic drugs in open-tubular capillary electrochromatography.

Metal organic frameworks (MOFs) have drawn broad attention as a novel stationary phase due to their highly porous structure, modifiable pores, large specific surface areas, and satisfactory stability. In this paper, histidine-zeolitic imidazolate framework-8 (His-ZIF-8) synthesized at room temperature was physically coated to the internal surface of the capillary column and the carboxymethyl-ß-cyclodextrin (CM-ß-CD) as the chiral selector was chemically bonded to the His-ZIF-8@capillary column. The prepared CM-ß-CD@His-ZIF-8@capillary column was used for the enantioseparation of amlodipine, propranolol, and atenolol in capillary electrochromatography. In contrast to the CM-ß-CD@capillary column without His-ZIF-8, the CM-ß-CD@His-ZIF-8@capillary column reveals significantly improved enantiodiscrimination performance for amlodipine (Rs : 0 → 2.29), propranolol (Rs : 0 → 1.69), and atenolol (Rs : 0 → 0.79). His-ZIF-8 concentration, buffer pH, buffer concentration, and the proportion of organic modifier were evaluated in detail with enantiomerically separating chiral molecules. The repeatability of intraday, day-to-day, and column-to-column have been discussed; the result was preferable, and the relative standard deviation (RSD) of separation parameters was <6.7%.

Metal organic framework- modified monolithic column immobilized with pepsin for enantioseparation in capillary electrochromatography.

Metal-organic frameworks (MOFs), defined as a class of microporous hybrid materials, are established by coordination of metal cations with functional organic ligands. In addition to outstanding porosity and large surface area, the structures and functions of MOFs can be designed and adjusted based on different destinations, which would be employed as stationary phases in various chromatographic modes. Pepsin, a class of protein, has been investigated as chiral selector owing to their unique interactions with analytes based on chiral or affinity selectivity. In this work, MOF-5 was exploited to grow on the support of poly (glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths by layer-by-layer self-assembly method. Pepsin was subsequently bonded with the carboxyl group of MOF-5 through amidation reaction. The ultimate pepsin@MOF-5@poly(GMA-co-EDMA) column was applied for enantioseparation of six basic chiral drugs by capillary electrochromatography with good resolution and repeatability. Compared with the pepsin modified monolithic column, the newly prepared column with MOF-5 shows significantly enhanced enantiomeric resolution, which reveals that MOFs-modified capillary monolithic columns lead a promising road to separation of racemates by chromatography.

Enhanced enantioseparation of drugs by capillary electrochromatography with a L-cysteine functionalized gold nanoparticle based stationary phase.

Nanoparticles, which have unique properties, have attracted growing attention in enantiomeric separation nowadays. In this paper, an L-cysteine functionalized gold nanoparticle (L-Cys-GNP) based capillary column was prepared and applied in separating drug enantiomers in capillary electrochromatography (CEC) with lactobionic acid (LA) as a chiral selector. Compared with bare fused-silica capillary columns, the capillary columns modified with L-Cys-GNPs showed excellent chiral separation performance. A series of parameters affecting the enantiomeric separation were systematically investigated.

Coassemble dopamine and GHK tripeptide into fluorescent nanoparticles for pH sensing.

Fluorescent nanostructures have been widely applied to biomedical researches and clinical diagnosis such as biolabeling/imaging/sensing and have even acted as therapy reagents. Peptide-based fluorescent nanostructures attract recent interest from biomedical researchers. Inspired by the natural existence of GHK-Cu complex with a growth factor-like effect in human blood, here we have developed a novel approach for designing nanosensors through the co-assembling of two kinds of biomolecules. By making best use of both π-π stacking between carbon rings and the easy-oxidation property of an important transmitter molecule, dopamine (DA), we successfully built up a supersensitive and robust fluorescent pH nanosensor by co-assembling oxidized DA (DAox ) with a tripeptide GHK. The GHK-DAox nanostructures have a quantum yield of 20.82%, which might be the brightest one among all the current co-assembling structures merely through unmodified biomolecules. We envision this approach could open a new avenue for not only hybrid nanostructure construction, but also may inspire the bioengineering of in vivo luminescent probes.

A novel ultrasensitive surface plasmon resonance-based nanosensor for nitrite detection.

Nitrite is a common food additive, however, its reduction product, nitrosamine, is a strong carcinogen, and hence the ultra-sensitive detection of nitrite is an effective means to prevent related cancers. In this study, different sized gold nanoparticles (AuNPs) were modified with P-aminothiophenol (ATP) and naphthylethylenediamine (NED). In the presence of nitrite, satellite-like AuNPs aggregates formed via the diazotization coupling reaction and the color of the system was changed by the functionalized AuNPs aggregates. The carcinogenic nitrite content could be detected by colorimetry according to the change in the system color. The linear concentration range of sodium nitrite was 0-1.0 µg mL-1 and the detection limit was determined to be 3.0 ng mL-1. Compared with the traditional method, this method has the advantages of high sensitivity, low detection limit, good selectivity and can significantly lower the naked-eye detection limit to 3.0 ng mL-1. In addition, this method is suitable for the determination of nitrite in various foods. We think this novel designed highly sensitive nitrate nanosensor holds great market potential.