Zirconium(IV) coordination-mediated rapid and versatile post-modification of polydopamine coating as stationary phase for open-tubular capillary electrochromatography.

In recent years, mussel-inspired polydopamine (PDA)-based materials have attracted significant attention in the field of open-tubular capillary electrochromatography (OT-CEC) owing to their diverse and appealing properties. However, previously established functionalized PDA coating-based CEC stationary phases predominantly relied on the latent reactivity of PDA with amine/thiol-containing molecules, limiting the types of applicable modifiers and requiring time-consuming reaction processes. Herein, we presented a versatile and efficient method for the facile and rapid fabrication of diverse functionalized PDA coatings as OT-CEC stationary phases through a Zr(IV) coordination-mediated post-modification strategy. Different kinds of modifiers, including octadecylamine (ODA), lauric acid (LA), and perfluorooctanoic acid (PFOA), were rapidly and robustly grafted onto the PDA coating, verified through multiple characterization techniques. The influences of preparation parameters on the grafting efficiency of the functionalized PDA coating were systematically investigated. Utilizing the Zr(IV)-mediated ODA-, LA- and PFOA-functionalized PDA-based OT-CEC columns, we achieved high-efficiency baseline separation of a series of neutral analytes with excellent repeatability, good stability, and long lifetime. Given the strong universality of the Zr(IV) coordination-mediated post-modification approach, our study provides an effective pathway for advancing the development of a wider range of functional PDA-based chromatographic stationary phases.

High-Efficiency Enzyme Assay and Screening of Enzyme-Inhibiting Nanomaterials Using Capillary Electrophoresis with Hierarchically Porous Metal-Organic Framework-Based Immobilized Enzyme Microreactor.

Enzyme-inhibiting nanomaterials have significant potential for regulating enzyme activity. However, a universal and efficient method for systematically screening and evaluating the inhibitory effects of various nanomaterials on drug target enzymes has not been established. While the integrated technique of immobilized enzyme microreactor (IMER) with capillary electrophoresis (CE) serves as an effective tool for enzyme analysis, it still faces challenges such as low enzyme loadability, unsatisfactory stability, and limited applicability. Herein, hierarchical porous metal-organic frameworks (HP-MOFs) were explored as high-performance enzyme immobilization carriers and stationary phases to develop a novel HP-MOFs-based IMER-CE microanalysis system for efficient online enzyme assay and systematic screening of enzyme-inhibiting nanomaterials. As a proof-of-concept demonstration, the model enzyme xanthine oxidase (XOD) was immobilized on a HP-UiO-66-NH2 coated capillary, serving as an efficient and durable IMER for screening potential XOD-inhibiting nanomaterials. The hierarchically micro- and mesoporous structure and superior enzyme loadability of as-prepared HP-UiO-66-NH2-IMER was intensively characterized, followed by systematic evaluation of the separation performance of HP-UiO-66-NH2 coated column and the enzyme kinetics of the immobilized XOD. Compared to the microporous UiO-66-NH2-IMER, the HP-UiO-66-NH2-IMER-CE system showed significant improvements in enzyme loading, maximum reaction rate, repeatability, and long-term stability. Furthermore, the established method was effectively employed to screen the XOD inhibitory activity of various nanomaterials, revealing that graphene oxide, single wall carbon nanotube and three other nanomaterials exhibited inhibitory potentials. The HP-MOFs-based microanalysis system can be easily expanded by modifying the types of immobilized enzymes and holds the potential to accelerate the identification and rational design of effective enzyme-inhibiting nanomaterials.

Phosphatase-mimicking Zr@PDA nanozyme with excellent dispersion stability for the detection of fructose 1,6-diphosphate.

Zr4+-doped polydopamine (Zr@PDA) nanozyme with phosphatase-like activity was synthesized by a one-pot hydrothermal method for the first time. Compared with previous representative phosphatase-mimicking nanozymes (i.e., CeO2 NPs, ZrO2 NPs and UiO-66), Zr@PDA not only exhibited higher dispersion stability in water, but also higher catalytical efficiency. Kcat/Km of Zr@PDA is 35 and 12 times that of UiO-66 and ZrO2 NPs, respectively, which would endow the Zr@PDA-based analytical methods with high sensitivity. As a demonstration, a novel colorimetric method based on Zr@PDA nanozyme was developed for sensitive detection of the drug fructose 1,6-diphosphate. The linear range is 1-15 µM with a detection limit as low as 0.38 µM.

MXene/ZnS/chitosan-cellulose composite with Schottky heterostructure for efficient removal of anionic dyes by synergistic effect of adsorption and photocatalytic degradation.

Nowadays, dye water pollution is becoming increasingly severe. Composite of MXene, ZnS, and chitosan-cellulose material (MX/ZnS/CC) was developed to remove anionic dyes through the synergistic effect of adsorption and photocatalytic degradation. MXene was introduced as the cocatalyst to form Schottky heterostructure with ZnS for improving the separation efficiency of photocarriers and photocatalytic performance. Chitosan-cellulose material mainly served as the dye adsorbent, while also could improve material stability and assist in generation of free radicals for dye degradation. The physics and chemistry properties of MX/ZnS/CC composite were systematically inspected through various characterizations. MX/ZnS/CC composite exhibited good adsorption ability to anionic dyes with adsorption capacity up to 1.29 g/g, and excellent synergistic effects of adsorption and photodegradation with synergistic removal capacity up to 5.63 g/g. MX/ZnS/CC composite performed higher synergistic removal ability and better optical and electrical properties than pure MXene, ZnS, chitosan-cellulose material, and MXene/ZnS. After compounding, the synergistic removal percentage of dyes increased by a maximum of 309 %. MX/ZnS/CC composite mainly adsorbs anionic dyes through electrostatic interactions and catalyzes the generation of •O2-, h+, and •OH to degrade dyes, which has been successfully used to remove anionic dyes from environmental water, achieving a 100 % removal of 50 mg/L dye.

[Deep eutectic solvents synergistic with carboxymethyl -ß-cyclodextrin on the improvement of chiral separation of metoprolol by capillary electrophoresis].

The physical and chemical properties of chiral drugs are very similar. However, their pharmacological and toxicological effects vary significantly. For example, one enantiomer may have favorable properties whereas the other may be ineffective or even have toxic side effects. Hence, exploring innovative strategies to improve enantiomeric resolution is of great importance. Metoprolol (MET) is a ß-receptor blocker used to treat hypertension, stable angina pectoris, and supraventricular tachyarrhythmia. Establishing chiral separation and analysis methods of MET enantiomers is important for enhancing the quality of chiral drugs. Capillary electrophoresis (CE) has the advantages of a small sample size, simple operation, high separation efficiency, and many alternative modes; therefore it is widely used in the field of chiral drug separation. The chiral selectors commonly used for CE-based chiral separation include cyclodextrin (CD) and its derivatives, polysaccharides, proteins, and macrocyclic antibiotics. CD is one of the most commonly used and effective chiral selectors for CE. The relatively hydrophobic structure inside the cavity and the relatively hydrophilic structure outside the cavity of CD enable it and chiral molecules to form inclusion compounds with different binding constants, thus achieving chiral separation. However, the use of CD alone as a chiral selector does not always yield satisfactory separation results. Hence, the addition of other additives, such as ionic liquids and deep eutectic solvents (DESs) to assist CD-based chiral separation systems has received extensive attention. Previous studies on the enantiomeric separation of MET by CE have focused on the addition of CD and its derivatives alone for separation. Few studies have been conducted on the synergistic addition of auxiliary additives to CD to improve the enantiomeric resolution of MET. In this study, three DESs, namely, choline chloride-D-glucose, choline chloride-D-fructose, and lactate-D-glucose, were used for the CE-based chiral separation of MET for the first time, and the synergistic effect of the DESs on the separation of MET enantiomers by CD-based capillary zone electrophoresis was speculated. For this purpose, an uncoated fused silica capillary with inner diameter of 50 µm, total length of 50 cm and effective length of 41.5 cm was used as the separation column. First, the effects of CD type, CD concentration, buffer pH, and buffer concentration on MET separation were investigated, and the optimal conditions (15 mmol/L carboxymethyl-ß-cyclodextrin (CM-ß-CD), pH=3.0, and 40 mmol/L phosphate buffer) were obtained. Other CE conditions were as follows: UV detection at 230 nm, applied voltage of 25 kV. All operations were carried out at 20 ℃. Next, three types of DESs were prepared as auxiliary additives via a mixed-heating method. The DESs were mixed in a 50 mL round-bottomed flask at a certain molar ratio and then heated in a water bath at 80 ℃ for 3 h until a clear and transparent liquid was obtained. The effects of different DESs and their mass fraction on chiral separation were subsequently studied. The optimal choline chloride-D-fructose mass fraction was ultimately determined to be 1.5%. The resolution of MET increased from 1.30 without DES to 2.61 with 1.5% choline chloride-D-fructose, thereby achieving baseline separation. Finally, the separation effect and mechanism were speculated. The MET chiral separation method established in this study is of great significance for improving the quality of chiral compounds and ensuring the safety and effectiveness of clinical drugs. Furthermore, it may be useful in the research and development of CE-based chiral separation techniques using CD derivatives with DESs.

Sulfonic Functionalized Polydopamine Coatings with pH-Independent Surface Charge for Optimizing Capillary Electrophoretic Separations.

Enhancing the pH-independence and controlling the magnitude of electroosmotic flow (EOF) are critical for highly efficient and reproducible capillary electrophoresis (CE) separations. Herein, we present a novel capillary modification method utilizing sulfonated periodate-induced polydopamine (SPD) coating to achieve pH-independent and highly reproducible cathodic EOF in CE. The SPD-coated capillaries were obtained through post-sulfonation treatment of periodate-induced PDA (PDA-SP) coatings adhered on the capillary inner surface. The successful immobilization of the SPD coating and the substantial grafting of sulfonic acid groups were confirmed by a series of characterization techniques. The excellent capability of PDA-SP@capillary in masking silanol groups and maintaining a highly robust EOF mobility was verified. Additionally, the parameters of sulfonation affecting the EOF mobilities were thoroughly examined. The obtained optimum SPD-coated column offered the anticipated highly pH-independent and high-strength cathodic EOF, which is essential for enhancing the CE separation performance and improving analysis efficiency. Consequently, the developed SPD-coated capillaries enabled successful high-efficiency separation of aromatic acids and nucleosides and rapid cyclodextrin-based chiral analysis of racemic drugs. Moreover, the SPD-coated columns exhibited a long lifetime and demonstrated good intra-day, inter-day, and column-to-column repeatability.

Study on the Selectivity of Molecular Imprinting Materials Determined through Hydrogen Bonding on Template Molecular Structures of Flavonoids.

Molecular imprinting technology is widely used for the specific identification of compounds, but the selective recognition mechanisms of the same compounds still need to be further studied. Based on differences in hydrogen bond size and orientation, molecularly imprinted polymers (MIPs) were designed to adsorb flavonols with the same parent core and different hydroxyl groups. A surface-imprinted material was designed with silicon dioxide as the carrier, myricetin as the template molecule, and methacrylic acid (MAA) as the functional monomer. Scanning electron microscopy (SEM), Brunauer-Emmett-Teller surface area (BET) analyses, Fourier-transform infrared spectroscopy (FT-IR), and other characterization experiments were carried out. The intrinsic mechanism of the MIPs was also explored. The MIPs showed good adsorption of myricetin and other flavonoids through hydrogen bonding and steric hindrance. The adsorption capacity was 3.12-9.04 mg/g, and the imprinting factor was 1.78-3.37. Flavonoids with different hydroxyl groups in different numbers and directions had different hydrogen bond strengths with functional monomers. R2, R4, and R1 on 2-phenylchromogenone had stronger electronegativity, and the hydroxyl group was also more likely to form and have stronger hydrogen bonds. The hydroxyl negativity and the degree of steric hindrance of flavonoids played a major role in the recognition of molecularly imprinted materials. This study is of great significance for the synthesis of and selection of templates for analogous molecular imprinting materials.

Boron nanosheets as a phosphatase mimicking nanozyme with ultrahigh catalytic activity for prodrug-based cancer therapy.

Boron nanosheets (BNSs) are reported as a new phosphatase mimicking nanozyme. Surprisingly, the catalytic rate of BNSs is up to 17 times those of known phosphatase mimicking nanozymes. By adding polyols and Lewis bases, the catalytic activity of BNSs was attributed to the Lewis acidity of the B centers of the BNSs. Theoretical investigation shows that the B centers are responsible for the catalytic hydrolysis of phosphoesters. Moreover, the biomimetic activity of the BNSs was further explored for enhancing anticancer therapy through nanozyme-catalyzed prodrug conversion.

Accelerating the Phosphatase-like Activity of Uio-66-NH2 by Catalytically Inactive Metal Ions and Its Application for Improved Fluorescence Detection of Cardiac Troponin I.

Compared with natural enzymes, nanozymes usually exhibit much lower catalytic activities, which limit the sensitivities of nanozyme-based immunoassays. Herein, several metal ions without enzyme-like activities were engineered onto Uio-66-NH2 nanozyme through postsynthetic modification. The obtained Mn+@Uio-66-NH2 (Mn+ = Zn2+, Cd2+, Co2+, Ca2+and Ni2+) exhibited improved phosphatase-like catalytic activities. In particular, a 12-fold increase in the catalytic efficiency (kcat/Km) of Uio-66-NH2 was observed after the modification with Zn2+. Mechanism investigations indicate that both the amino groups and oxygen-containing functional groups in Uio-66-NH2 are the binding sites of Zn2+, and the modified Zn2+ ions on Uio-66-NH2 serve as the additional catalytic sites for improving the catalytic performance. Furthermore, the highly active Zn2+@Uio-66-NH2 was used as a nanozyme label to develop a fluorescence immunoassay method for the detection of cardiac troponin I (cTnI). Compared with pristine Uio-66-NH2, Zn2+@Uio-66-NH2 can widen the linear range by 1 order of magnitude (from 10 pg/mL-1 µg/mL to 1 pg/mL-1 µg/mL) and also lower the detection limit by 5 times (from 4.7 pg/mL to 0.9 pg/mL).

Chitosan-alginate sponge with multiple cross-linking networks for adsorption of anionic dyes: Preparation, property evaluation, mechanism exploration, and application.

A chitosan-alginate sponge (CAS) with multiple cross-linking networks was developed using chitosan, sodium alginate, polyvinyl alcohol, and glutaraldehyde to adsorb and enrich the anionic dyes form the food samples. The multiple networks in CAS refer to the electrostatic cross-linking network, hydrogen bonding cross-linking network, and covalent cross-linking network. Compared with pure chitosan and alginate sponges, the CAS showed better three-dimensional network structure, mechanical behavior, and stability, which is benefit by multiple cross-linking networks. The physical and chemical properties of CAS were systematically studied by a series of characterizations. The adsorption performance of CAS on anionic dyes was inspected with different dye concentration, time, temperature, and pH conditions. CAS exhibited a good and stable adsorption property to amaranth, carmine, and sunset yellow with the saturation adsorption capacity of 94.34, 111.5, and 80.05 mg∙g-1, respectively. Furthermore, CAS performed outstanding selectivity to anionic dyes with the selectivity factor up to 16.99. Through electrostatic potential analysis, it is inferred that CAS mainly adsorbs anionic dyes through electrostatic interactions. CAS showed satisfactory reusability, maintaining 97 %-99 % of adsorption performance after six cycles of recycling. Finally, CAS was combined with high-performance liquid chromatography for the enrichment and detection of anionic dyes in candy and cocktail samples, achieving the enrichment factor up to 84.77.

Protein Recognition Based on Temperature-Stimulated Multiparameter Response Virtual Array Sensing Strategy.

In the field of array sensing, researchers are committed to miniaturizing array sensing systems while ensuring the acquisition of multiple sensing information. Here, a new strategy called "stimulus responsive array sensing" was presented to obtain virtual multiple sensing without constructing multiple physical sensing units. Based on bioluminescence resonance energy transfer, where luciferase acts as the donor and temperature stimulus response polymers act as the receptors, by using only one sensing unit to output multiple stimulus responsive sensing signals in temperature dimension, an equivalent array sensing could be achieved. This strategy can distinguish and quantify a variety of proteins. More importantly, glucose responsive monomers were doped in polymers; thus, more virtual sensing units can be further increased to obtain more sensing signals, greatly increasing the accuracy of protein recognition, and it can also be used to differentiate several compositions of protein under different glucose concentrations in urine caused by different renal diseases. The results show the potential of the "stimulus responsive array sensing" for analyzing molecular compositions in complex biological systems and show a new tack in array sensing.

[Research progress on the construction and applications of metal-organic frameworks in chromatographic stationary phases].

Metal-organic frameworks (MOFs) are a class of porous crystalline materials composed of metal centers or clusters assembled with organic ligands. These materials possess excellent properties, such as large surface areas, high porosities, uniform pore sizes, and diverse structures. Thus, MOFs have been widely applied in various fields, including catalysis, adsorption, sensing, sample pretreatment, and chromatographic separation. The applications of MOFs as stationary phases for chromatographic separation and analysis have attracted considerable attention from the research community in recent years. Compared with traditional chromatographic stationary phases, such as mesoporous silica, nanoparticles, and porous layers, MOFs possess flexible and tunable pore sizes and structures, thereby enabling precise control over their intermolecular interactions. Furthermore, the wide range of functional ligands and topologies of MOFs could potentially facilitate the separation and analysis of complex samples. These unique advantages render MOFs highly suitable for constructing novel chromatographic stationary phases.This article focuses primarily on the construction methods of MOFs as chromatographic stationary phases, and provides an overview of the latest research advancements in their applications in several chromatographic separation techniques such as high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrochromatography (CEC). The existing methods for the preparation and construction of MOFs-based chromatographic stationary phases are classified and evaluated. The construction methods for MOFs as stationary phases for HPLC mainly include filling, precursor-doped polymerization, and post-modification. The construction methods for MOFs as stationary phases for GC predominantly include in situ growth, static coating, and dynamic coating. The stationary phases for CEC can be categorized into packed columns, monolithic columns, and open-tubular columns. Compared with monolithic and packed columns, open-tubular CEC (OT-CEC) offers numerous advantages, including a more flexible and convenient preparation method, enhanced compatibility with various separation media, and higher separation efficiency. Consequently, OT-CEC has emerged as an important method for investigating the preparation of stationary phases for CEC. Several methods such as physical adsorption, covalent attachment, and electrostatic interactions have been developed for the preparation and modification of MOFs-based CEC stationary phases, and extensive studies have been conducted to optimize the performance and applications of MOFs in OT-CEC. However, the existing methods for constructing MOFs-based chromatographic stationary phases present certain limitations. Therefore, the selection of the appropriate MOFs, optimization of their preparation methods, and examination of their performance in different separation modes have become the focus of intensive research.This review also summarizes the different analytical targets (e. g., chiral small molecules, biomacromolecules, and nonchiral molecules) and corresponding separation effects achieved using various MOFs-based chromatographic stationary phases. Finally, future studies focusing on the development of MOFs as chromatographic separation media are discussed. Overall, this review provides a valuable reference for the rational construction and practical applications of advanced MOFs-based chromatographic stationary phases.

Strategy of Choosing Templates in Molecular Imprinting to Expand the Recognition Width for Family-Selectivity.

The class-selective molecular-imprinted polymers (MIPs) have shown the recognition ability to multiple targeted molecules through using one or multiple templates. However, choosing the right templates, the core problem, still lacks a systemic guide and decision-making. In this work, we propose a strategy of selecting templates through expanding the recognition width for the improvement of class-selectivity. First, three families of genotoxic impurity (GTI) were selected as model objects, and the spatial size and binding energy of each GTI-monomer complexes were obtained and compared by computational simulation. The two indexes of energy width (WE) and size width (WL) were introduced to compare the similarity and differences on the two recognition factors, binding strength and spatial size, among these GTIs in each family. Through shortening the width to increase similarity on binding energy and size, the dual templates in the aromatic amines (AI) family and sulfonic acid esters (SI) family were successfully selected. Correspondingly, the prepared dual-template MIPs in the two GTI families can simultaneously recognize all the GTIs comparing with that of single template MIP, respectively. Meanwhile, through comparing the adsorption capacity of the selected template and its analogues in one GTI family, the recognition efficiency of the dual-template MIPs was higher than that of the single-template MIP. This indicates that though using the selected right templates, the higher class-selectivity and the larger recognition width can be realized. Thus, this work can solve the problem of blind template selection, and provide the useful theoretical guidance for designing family-selective molecular imprinting.

Improved selectivity of molecularly imprinted polymers based on the synergistic action of hydrogen bond and electrostatic interaction.

Based on the synergistic action of hydrogen bond and electrostatic interaction, provided by methacrylic acid and 2-aminoethyl ester hydrochloride (FM2), respectively, novel molecularly imprinted polymers (SA-MIPs) were designed to improve its selective recognition ability. Diclofenac sodium (DFC) was chosen as the template molecule of this study. The interaction and their recognition sites between two functional monomers and templates were confirmed by nuclear magnetic resonance hydrogen spectroscopy. Because of the synergistic action of hydrogen bond and electrostatic interaction, the imprinting factor (IF) of SA-MIPs (IF = 2.26) is superior to the corresponding monofunctional monomer imprinting materials (IF = 1.52, 1.20) and the materials using two functional monomers with an only single type of interaction (IF = 1.54, 1.75). The results of selective adsorption experiments indicate that the selective recognition ability of SA-MIPs is significantly better than that of the other four MIPs, and the difference in selectivity coefficient for methyl orange is the largest between SA-MIPs and the MIPs only using FM2, which is about 70 times. In addition, x-ray photoelectron spectroscopy was used to verify the interaction between SA-MIPs and the template. This work and its explanation of the interaction mechanism at the molecular level will be helpful for the rational design of novel MIPs with higher selectivity. Besides, SA-MIPs have good adsorption performance (37.75 mg/g) for DFC in aqueous solutions, which could be used as potential adsorption materials for the effective removal of DFC in the aquatic environment.

Mixed-Solvent-Mediated Strategy for Enhancing Light Absorption of Polydopamine and Adhesion Persistence of Dopamine Solutions.

Mussel-inspired polydopamine (PDA) and its derivative materials have exhibited a huge potential as a facile and versatile route to fabricate multifunctional coatings on virtually any substrate surface. However, their performance and applicability are frequently obstructed by limited optical absorption in visible regions of PDA and poor surface adhesion persistence of dopamine solutions. Herein, we report a facile strategy to improve these problems by rationally regulating the dopamine polymerization pathway through mixed-solvent-mediated periodate oxidation of dopamine. The spectral analysis, ultrahigh-performance liquid chromatography coupled with high-resolution mass spectrometry, and density functional theory simulations systematically demonstrate that the mixed-solvent reaction systems can effectively accelerate the periodate-induced formation of cyclized moieties in the PDA microstructure and inhibit their further oxidative cleavage, thus contributing to narrowing the inherent energy band gap of PDA and improving the long-lasting surface deposition performance of aged dopamine solutions. Moreover, the newly constructed cyclized species-rich PDA coatings have excellent surface uniformity and significantly enhanced chemical stability. Benefiting from these fascinating properties, they have been further used for permanent dyeing of natural gray hair with remarkably improved blackening effect and excellent practicability, which exhibited their promising prospect in real-world applications.

Chiral zinc oxide functionalized quartz crystal microbalance sensor for enantioselective recognition of amino acids.

Chiral transition metal oxides with tunable structures and multiple physicochemical features have been increasingly applied for chiral sensing and detection. In this work, chiral zinc oxide (ZnO) was first applied as selector to construct quartz crystal microbalance (QCM) sensor for enantioselective recognition of amino acids. The chiral ZnO was prepared by a methionine-induced self-assembly strategy and its high topological chirality was confirmed by several techniques such as circular dichroism spectrum. The chiral discrimination factors were calculated by frequency shifts in response to aspartic acid, phenylalanine, lysine and arginine on L-ZnO surface, achieving 1.89 ± 0.04, 1.76 ± 0.11, 1.66 ± 0.07 and 1.54 ± 0.09, respectively. Notably, L-enantiomers preferred stronger absorptions on L-ZnO surface as compared to D-forms. It was further found that this sensor was appropriate for quantitative analysis and enantiomer excess analysis and adsorption kinetics study. Furthermore, molecular docking revealed the recognition mechanism, where chiral distinction was caused by the different steric interactions between enantiomers and chiral ZnO. This method enjoyed merits of high enantioselectivity, simple preparation and low cost, offering newly chiral sensing method for other molecules.

Zirconium-amino acid framework as a green phosphatase-like nanozyme for the selective detection of phosphate-containing drugs.

The zirconium-amino acid framework MIP-202(Zr) was reported as a green phosphatase-like nanozyme for the first time. Moreover, its phosphatase-like activity can be inhibited by phosphate-containing drugs. Based on this finding, a universal fluorimetric strategy for sensing phosphate-containing drugs was developed. The detection limit was as low as 2 ng mL-1 for the model drug alendronate sodium. This strategy exhibits excellent selectivity over other non-phosphate-containing drugs and will broaden the applications of phosphatase-like nanozymes in clinical pharmacy.

Homomesoporous Metal-Organic Framework for High-Performance Electrochromatographic Separation.

Metal-organic frameworks (MOFs) have exhibited tremendous potential in the area of separation science. However, most of the developed MOF-based stationary phases contained only microporous structures and suffer from limited separation performance. Herein, homomesoporous MOFs with excellent mass transfer capability and strong thermodynamic interactions are first explored as the novel stationary phase for high-performance capillary electrochromatographic separations. As a proof of concept, noninterpenetrated mesoMOF-1 with uniform mesopore sizes (22.5 × 26.1 Å) and good stability was facilely grown on the inner surface of capillaries and applied as a homomesoporous MOF coating-based stationary phase for high-efficiency electrochromatographic separation. Seven types of analytes with different molecular dimensions were all baseline separated on a mesoMOF-1 coated column with high theoretical plate numbers and excellent repeatability, exhibiting significantly improved separation selectivity and column efficiency in comparison to a microporous HKUST-1 coated column. The maximum column efficiencies of the mesoMOF-1 coated column for substituted benzenes and halobenzenes reached up to 1.4 × 105 plates/m, and its mass loadability was also much higher than that of the HKUST-1 coated column. In addition, based on the analysis of adsorption kinetics and chromatographic retention behaviors, the interaction and retention mechanisms of different molecular-weight analytes on mesoMOF-1 coated stationary phases were systematically explored and disclosed in detail. These results indicate that the homomesoporous MOF-based stationary phase can effectively balance the kinetic diffusion (mass transfer capability) and thermodynamic interactions (the strength of adsorption interaction), having great potential for high-performance chromatographic separation.

Preparation of dummy molecularly imprinted polymers for selective extraction of aromatic amine genotoxic impurities.

To ensure drug safety, the quality monitoring of genotoxic impurities (GTIs) which have very trace content in medicine is important. Therefore, it should be established an efficient sample pretreatment method to extract GTIs to achieve specific enrichment. In this work, dummy template molecular imprinting technology (DMIT) was used as dummy template molecule (DTM) to substitute for the target molecule (TM) for established the pretreatment of the sample containing aromatic amine GTIs. A novel strategy for screening out DTM by calculation of computer simulation is established, where the binding energy between the template and functional monomer has the relatively lowest value (-9.60 kcal/mol). Then dummy template molecular imprinted polymer (DMIP) was prepared by bulk polymerization according to the molar ratio of template molecule-functional monomer-crosslinker = 1:4:8, the prepared DMIP exhibited the highest adsorption (Q = 8.6 mg/g) and good blotting effect (IF = 1.3) and can simultaneously adsorb three aromatic amine GTIs. The optimal adsorption conditions were obtained by conditional optimization of solid phase extraction (SPE). The solution of pH 7 was chosen as the loading condition, and methanol/acetic acid (90:10, v/v) was chosen as the elution condition. Finally, we determined 2, 6-dichloroaniline in diclofenac sodium at a 5 ppm level and p-toluidine as the TMs in torasemide sample at 10 ppm by using DMIT-based solid phase extraction and analysis by HPLC, it satisfied the quality control of GTIs in pharmaceutics. DMIT by this strategy has great potential in the sample preparation of GTIs.

Study the interactions between multiple flavonoids and bovine serum albumin by the developed equilibrium dialysis.

The therapeutic function of traditional Chinese medicine (TCM) is based on the combination effect of multiple active ingredients. However, the current pharmacological studies mainly focus on the protein binding of the single component from TCM, which is difficult to explain the overall therapeutic mechanism. Thus in this work the equilibrium dialysis method combined with high performance liquid chromatography (HPLC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to study the interactions between multi-components and protein. Firstly, the binding constants of seven different structural types of flavonoids with bovine serum albumin (BSA) were determined. The results showed that the binding affinity of flavones and flavonols with BSA was stronger than that of dihydroflavonoids, and the substitution of glycosides would reduce the binding affinity with BSA. The results of competitive displacement experiment showed that there existed competitive interactions among the four flavonoids (rutin, luteolin, hesperetin and kaempferol). The binding constants of flavonoids to BSA were significantly changed under the condition of multi-components coexistence. Especially, the binding constant of hesperetin to BSA increased from 9.46 × 104 L/mol to 1.49 × 106 L/mol under the coexistence of rutin. The results of fluorescence spectroscopy showed that the reason for competitive binding was that the four flavonoids were mainly bound to the IIA region of BSA. Finally, the method was successfully applied to study the binding of multiple components in Radix Scutellariae (RS) extract with BSA. Five flavonoids in RS extract were identified by UPLC-MS/MS, they had different degrees of binding to BSA, among which oroxylin A had the strongest binding degree. In conclusion, the equilibrium dialysis was reliable and sufficiently accurate for study of the interaction between multi-components or TCM extract and protein, which can provided a theoretical basis for the scientific explanation of the overall treatment mechanism of TCM.