Efficient and Selective Adsorption of cis-Diols via the Suzuki-Miyaura Cross-Coupling-Modified Phenylboronic-Acid Functionalized Covalent Organic Framework.

In this work, a functional group (boronic acid) was modified onto a covalent organic framework (COF) using the Suzuki-Miyaura cross-coupling reaction to obtain a phenylboronic acid-functionalized covalent organic framework (BrCOF-PBA). This product was used as a selective adsorbent and largely as an efficient solid-phase extractant of flavonoids containing cis-diol structures like quercetin (QUE). Five or six-membered cyclic esters generated from the COF were characterized, and some physicochemical studies were performed, resulting in excellent chemical stability and crystallinity, high specific surface area, stable pore structure, and regular pore size. Unique selectivity of BrCOF-PBA was observed toward QUE and exhibited a huge adsorption capacity (213.96 mg g-1) in a relatively short time (90 min). In contrast, the adsorption properties of morin (MOR) and kaempferol (KAE) with a certain degree of chemical similarity to QUE were only 27.62 and 21.76 mg g-1, respectively. BrCOF-PBA also demonstrated good reusability and robustness, making it an attractive composite material for further analytical applicability.

Portable paper-based probe for on-site ratiometric fluorescence determination of total flavonol glycosides in plant extract using smartphone imaging.

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al3+/Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al3+/Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80 µg mL- 1 and a lower detection limit of 2.07 µg mL- 1. The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al3+/Eu-MOF/paper-based probe used for total flavonol glycosides determination.

Study on performance of mimic uricase and its application in enzyme-free analysis.

Nanozymes were the novel research field to replace natural enzymes because of stability and low cost. However, the research on nanozymes was mainly focused on peroxidase, and there was little research about nanozymes with oxidase-like activity, especially mimic oxidase of small molecules related to human physiology. High levels of uric acid (UA) in the body can cause hyperuricemia and gout. And natural uricase cured this disease because it could oxidize UA. The oxidase-like activity of mixed valence state metal organic frameworks with cerium (MVSM) had been studied, but MVSM was found to have uricase-like activity in this article. The catalytic process of UA with MVSM was studied by a variety of analytical methods, which was similar to the natural uricase except for further oxidation of H2O2. The catalytic activity constants of MVSM were acquired by the Michaelis-Menten equation. MVSM had a better ability to catalyze UA in in vivo and in vitro experiments. An enzyme-free analysis-based mimic uricase for UA was established. All the experimental results proved that MVSM had a good prospect to replace the natural uricase. A nanomaterial, mixed valence state Ce-MOF (MVSM), with uricase-like activity has been found in vivo and in vitro. This material has potential to be a fluorescent analysis for detecting uric acid without uricase.

Fluorescence determination of quercetin in food samples using polyhedron-shaped MOF@MOF(NUZ-8) based on NH2-UiO-66 and ZIF-8.

A new metal-organic framework compound (MOF@MOF, NUZ-8) comprised of NH2-UiO-66 and ZIF-8 under the polyvinylpyrrolidone (PVP) as the structure modifier was synthesized through an internal extended growth method (IEGM). The resulting NUZ-8 emerged the unreported unique polyhedron shape and showed considerable specific surface area (1466.1862 m2/g), excellent adsorption capacity, and fluorescence. NUZ-8 was used as a probe for the rapid optical detection of natural antioxidant quercetin (QCT). Its outstanding selectivity and sensitivity to QCT are derived from the fact that NH2-UiO-66 acted as an optical tentacle to perceive QCT in virtue of its luminescence advantages, and ZIF-8 realized the selective enrichment of the QCT through its electron-rich framework structure. The experiments were carried out at an excitation wavelength of 335 nm and an emission wavelength range of 370-530 nm. Under conditions of the investigation, this probe realized the rapid detection of QCT and considerable adsorption capacity with wide linearity (0.3-80 µM), a low detection limit (0.14 µM), and acceptable recoveries (84.0-97.0%) in red wine samples, properties which were superior to many other detection platforms. The synthesis and the use of the above polyhedral composite provide guidance for the application of the IEGM in enhancing chemical sensing and instant determination of drugs.Graphical abstract Flow chart of this paper.

Nanozyme based on graphene oxide modified with Fe3O4, CuO, and cucurbit[6]uril for colorimetric determination of homocysteine.

A nanozyme based on graphene oxide modified with Fe3O4 NPs, CuO NPs, and cucurbit[6]uril has been successfully fabricated by a simple sonochemical technique. By employing CB[6] as a specific binding pocket and Fe3O4@CuO-GO as a peroxidase mimic, this novel nanozyme (BN I) is equipped with molecular recognition ability and enhanced peroxidase-like activity. On the basis of the inhibition effect of homocysteine (Hcy) towards the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by BN I, a simple colorimetric method is established for the sensitive and selective determination of Hcy. This proposed method displays a good linear response in the range 5-200 µM with a detection limit of 1.8 µM. In the practical assay of human plasma samples, the relative standard deviations (RSD) are lower than 11% and the recoveries are between 98.0 and 104.9%. In the assay of human urine samples, the RSD are below 9.0% and the recoveries range from 94.0 to 103.5%. The colorimetric method presented offers a convenient and accurate way for the determination of biomarkers in point-of-care testing (POCT).

Halloysite nanotubes in analytical sciences and in drug delivery: A review.

Halloysite (HNT) is a natural inorganic mineral that has many applications in manufacturing. This review (with 192 references) covers (a) the chemical properties of halloysites, (b) the effects of alkali and acid etching on the loading capacity and the release behavior of halloysites, (c) the use of halloysite nanotubes in analytical sciences and drug delivery, and (d) recent trends in the preparation of magnetic HNTs. Synthetic methods such as co-precipitation, thermal decomposition, and solvothermal method are discussed, with emphasis on optimal magnetization. In the analytical field, recent advancements are summarized in terms of applications of HNT-nanocomposites for extraction and detection of heavy metal ions, dyes, organic pollutants, and biomolecules. The review also covers methods for synthesizing molecularly imprinted polymer-modified HNTs and magnetic HNTs. With respect to drug delivery, the toxicity, techniques for drug loading and the various classes of drug-halloysite nanocomposites are discussed. This review gives a general insight on the utilization of HNT in analytical determination and drug delivery systems which may be useful for researchers to generate new ideas. Graphical abstract Schematic presentation of the structure of halloysite nanotubes, selected examples of modifications and functionalization, and represetative field of applications.

Less interference fluorescence analytical strategy: Bridging substance-triggered ratiometric sensor with convenient preparation and application.

High interference and narrow application range are key of bottleneck of recent fluorescence analysis methods, which limit their wide application in the sensing field. Therefore, to overcome these disadvantages, a ratiometric fluorescence sensing system utilizing berberine (BER) and silver nanoclusters protected by dihydrolipoic acid (DHLA-AgNCs) was constructed for the first time in this work, to achieve determination of BER and daunorubicin (Dau). BER aqueous solution (non-planar conformation) has no fluorescence emission. When it was mixed with DHLA-AgNCs, the conformation of BER became planar, producing fluorescence emission at 515 nm besides the fluorescence emission peak of DHLA-AgNCs at 653 nm. With the increase of BER concentration added in system, the fluorescence intensity of BER (planar conformation) at 515 nm increased obviously and the fluorescence intensity of DHLA-AgNCs decreased slightly. Therefore, the dual emission fluorescence sensing system was constructed based on a fluorescence substance and non fluorescence substance, to achieve determination of BER. Meanwhile, based on the bridging effect of BER and fluorescence resonance energy transfer effect from Dau, the altering of two peaks intensity was utilized to achieve determination of Dau. Thus, this dual emission sensing system can not only be used for fluorescence analysis of BER and its analogues, but also based on the bridging effect of BER, allowing the determination of Dau and its analogues that could not be directly measured with silver nanoclusters, expanding the application range of traditional dual emission detection systems. Meanwhile, this system has strong anti-interference ability and low toxicity to the human body and less pollution to the sample and environment. This provides a new direction and universal research strategy for the construction of new fluorescence sensing systems in the future for the analysis of target substances that cannot be directly detected with conventional fluorescence analysis methods.

Polyethyleneimine in designed nanocomposite based magnetic halloysite nanotubes for extraction and determination of gallic acid in green tea.

An innovative and simple nanocomposite denoted as MHNTs@PEI was synthesized for gallic acid (GA) analytical sample pretreatment. Polyethyleneimine (PEI) functionalized was binded onto magnetic halloysite nanotubes (MHNTs) to inhence adsorption capacity. MHNTs@PEI was obtained only through two steps modification (amination and PEI modification). Characterizations showed that there are layers of synthetic PEI on the tubular structure of the material and magnetic spheres on its surface, both indicating successful synthesis of the nanocomposite. Furthermore, the adsorption isotherms and kinetic modeling showed that the Langmuir model and pseudo-first-order model fit the adsorption data, respectively. MHNTs@PEI achieved an adsorption capacity of 158 mg·g-1. Overall, the abundant adsorption sites significantly improved the adsorption performance of the MHNTs@PEI. Regeneration tests demonstrated that the MHNTs@PEI exhibits effective adsorption, even after undergoing five consecutive cycles. Optimization of key parameters (ratio, volume of elution, elution time and frequency) in the process of adsorption and desorption was also conducted. The limit of detection (LOD) and that of the quantification (LOQ) were 0.19 and 0.63 µg·mL-1, respectively, and the recoveries were 95.67-99.43 %. Finally, the excellent magnetism (43.5 emu·g-1) and the adsorption feature of MHNTs@PEI enabled its successful utilization in analytical sample pretreatment through the extraction of GA from green tea.

Discovery of a Potent Dual Son of Sevenless 1 (SOS1) and Epidermal Growth Factor Receptor (EGFR) Inhibitor for the Treatment of Prostate Cancer.

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.

Preparation of molecularly imprinted polymers on the surface of magnetic carbon nanotubes with a pseudo template for rapid simultaneous extraction of four fluoroquinolones in egg samples.

Fluoroquinolones (FQs) have emerged as one of the most important class of antibiotics. Due to their low concentration in bio-matrix samples which contain a lot of interfering substances, the efficient solid phase extraction and accurate determination of FQs remain a challenge. In this paper, a new strategy for the isolation and enrichment of FQs from egg samples was obtained by molecularly imprinted polymers on the surface of magnetic carbon nanotubes (MCNTs@MIP), which not only can be collected and separated rapidly by an external magnetic field, but also have a high specific surface area, outstanding mechanical properties and specific recognition for FQs. MCNTs@MIP were prepared using ofloxacin as a pseudo template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker. The characteristics of the MCNTs@MIP were assessed by transmission electron microscopy (TEM), multipoint Brunauer-Emmett-Teller (BET) analysis, vibrating sample magnetometry (VSM), X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. The results of the adsorption experiments not only demonstrated rapid dynamic adsorption but also showed a high selectivity toward FQs. An extraction method using MCNTs@MIP coupled with high performance liquid chromatography (HPLC) was developed for the determination of four FQs in egg samples. The recovery of four FQs ranged from 95.2% ± 3.2% to 100.7% ± 3.1% and the detection limits ranged from 0.25-0.40 ng g(-1). The results demonstrate that the proposed method based on pseudo template MCNTs@MIP is a promising approach for the preconcentration, purification, and simultaneous analysis of four FQs in bio-matrix samples.

Loading behavior of gatifloxacin in urine and lake water on a novel magnetic molecularly imprinted polymer used as extraction sorbent with spectrophotometric analysis.

The loading behavior of gatifloxacin (GTFX) in human urine and lake water on a novel magnetic molecularly imprinted polymer used as extraction sorbent with UV-Visible spectrometric analysis has been studied. The magnetic polymers had been prepared using GTFX as template molecule and Fe3O4 as magnetic component. The polymer had been characterized by SEM, Fourier-transform infrared spectrometry, and appropriate magnet separator. Parameters affecting the extraction efficiency were evaluated in order to achieve optimal loading and reduce nonspecific interactions. Good linearity of the method had been obtained in the range between 0.25 and 15 µg mL(-1) by UV-Vis spectrophotometry at 286 nm with spectral analysis from 240 to 400 nm. The method detection and quantification limits of GTFX in water were 0.075 and 0.25 µg mL(-1), respectively. This study showed good selectivity and loading efficiency (α > 2) of the polymers. The loading behavior of GTFX in the samples spiked on polymers had been obtained and each other with recovery higher than 91% with RSD% between 2.5 and 3.3. No pretreatment of samples were needed and no interference of compounds in urine and lake water were observed during adsorption.

Research progress of sensors based on molecularly imprinted polymers in analytical and biomedical analysis.

Molecularly imprinted polymers (MIPs) have had tremendous impact on biomimetic recognition due to their precise specificity and high affinity comparable to that of antibodies, which has shown the great advantages of easy preparation, good stability and low cost. The combination of MIPs with other analytical technologies can not only achieve rapid extraction and sensitive detection of target compounds, improving the level of analysis, but also achieve precise targeted delivery, in-vivo imaging and other applications. Among them, the recognition mechanism plays a vital role in chemical and biological sensing, while the improvement of the recognition element, such as the addition of new nanomaterials, can greatly improve the analytical performance of the sensor, especially in terms of selectivity. Currently, due to the need for rapid diagnosis and improved sensing properties (such as selectivity, stability, and cost-effectiveness), researchers are investigating new recognition elements and their combinations to improve the recognition capabilities of chemical sensing and bio-sensing. Therefore, this review mainly discusses the design strategies of optical sensors, electrochemical sensors and photoelectric sensors with molecular imprinting technology and their applications in environmental systems, food fields, drug detection and biology including bacteria and viruses.

Preparation and Application of Nanozymes with Uricase-Like Activity Based on Molecularly Imprinted Polymers.

Nanozymes have advantages over natural enzymes in terms of efficiency, stability, and economy. MVSM (Mixed Valence State MOF) is a nano-oxidase with uricase-like activity that may catalyze uric acid (UA) in the body into allantoin and H2 O2 to treat gout and hyperuricemia by substituting natural uricase. However, it cannot specifically identify and choose UA. To increase the selectivity and affinity of MVSM for UA, the composite material MVSM@MIP is innovatively synthesized using a new synthetic approach termed the "two-step synthesis method," which may prevent UA from being oxidized by MVSM during manufacture in this study. At the same time, this study also provides experimental proof of the effective creation of the material, the advantages of the "two-step synthesis approach," and the high selectivity and affinity of MVSM@MIP for UA. Based on these findings, the suggested technique may be used to effectively catalyze uric acid in human urine with high activity.

Degradation study of rutin as template from magnetic composite molecularly imprinted polymer supernatant samples by liquid chromatography-mass spectrometry.

Compound structure change of the template molecule from rutin samples might affect the selectivity and adsorption of molecularly imprinted polymers based on magnetic halloysite nanotubes (MHNTs@MIPs). In the present study, not only MHNTs@MIPs were successfully characterized by TEM, SEM, EDS, FT-IR, TGA and VSM, but related compounds and potential degradation factors of template molecule rutin were also investigated in the polymerization and elution process of MHNTs@MIPs by high-performance liquid chromatography together with photodiode array and tandem mass spectrometry (HPLC-PDA-MS/MS) in negative ion mode. Nine flavonol components were detected in rutin active pharmaceutical ingredient samples, such as rutin, isoquercetrin, kaempferol-3-O-rutoside, isorhamnetin-3-O-rutoside, quercetin, kaempferol, isorhamnetin and two unknown triglycosides. Under acidic, basic, oxidative and solvent conditions, two common degradants with negative ESI-MS ions at m/z 317 and 349 were found. Meanwhile, protocatechuic acid and methyl ester were also observed as two characteristic oxidative degradants. Compared to above degradation results, rutin-dimethylsulfoxide adduct and oxidative degradant were observed in the synthesis supernatant, which demonstrated that appropriate solvents and strict control of the oxygen level were critical in the synthesis process. Therefore, degradation studies provide a solid foundation for the optimization of MHNT@MIP synthesis with rutin as a template, which can be potentially applied to other templates for further material performance investigation.

Study Destination Choice and Career Preferences of International Students at China Pharmaceutical University.

This study had two main thematic aims: first, to determine the factors that influenced the choice of international students at China Pharmaceutical University (CPU) to consider China as a study destination; second, to determine the career preferences of international students upon completion of their various programs of study. As a cross-sectional study, relevant data were collected from undergraduate pharmacy students and postgraduates using a self-administered questionnaire. On the whole, the five most important pull factors that influenced the choice of China as the study destination for the respondents were: (1) quality of education, (2) quality of academic staff, (3) security, (4) desire to obtain a certificate from a foreign country and (5) availability of scholarship opportunities. With respect to the career choices, the top three career preferences of the international students were: (1) to work in the pharmaceutical industry (i.e., pharmaceutical manufacturing companies), (2) to practice clinical pharmacy and (3) to seek employment opportunities outside their countries. This study provides additional details on why China has gradually become a study destination of choice for international students. The career preferences of students could be useful in the design of academic programs that could meet their job aspirations.

Recent Advances in Construction and Application of Metal-Nanozymes in Pharmaceutical Analysis.

Nanozymes, made of emerging nanomaterials, have similar activity to natural enzyme and exhibit promising applications in in the fields of environment, biology and medicine, and food safety science. In recent years, with the deep finding and research to nanozymes by researchers, its application in field of pharmaceutical analysis has emerged gradually, possessing great significance in drug safety evaluation and quality control. This review summarizes the construction of metal nanozymes, strategies to improve their performance and their application in pharmaceutical detection and analysis, especially in detection of target analytes consisting of small molecule medicine macromolecule, toxic and others, which proposes theoretical foundation for development of nanozymes in this field. At the same time, it also provides opportunities and challenges for the construction and application of new nanozymes.

Novel composite nanomaterials based on magnetic molecularly imprinted polymers for selective extraction and determination of rutin in fruit juice.

In this work, with the attempt to further improve the selectivity, magnetism and loading proportion of existing adsorbents, a novel composite (MGO/MHNTs@MIPs) was synthesized by electrostatically combining molecularly imprinted polymer based on the surface of magnetic halloysite nanotubes (MHNTs@MIPs) with magnetic graphene oxide (MGO). Then some characterizations were done to prove its successful synthesis. Besides, the bonding experiment showed that it possessed a loading capacity of up to 132 mg·g-1, and the adsorption behavior of MGO/MHNTs@MIPs was elucidated by Langmuir isotherm model and Pseudo-second order model. By comparing its adsorption capacity to analogues, we concluded that the MGO/MHNTs@MIPs with the MHNTs@MIPs as basic elements exhibited higher selectivity (imprinting factor = 2.25) than that of MGO/MHNTs@NIPs based on MHNTs@NIPs for template rutin. Furthermore, a series of solid phase extraction conditions were optimized, and then the materials were used for the extraction and detection of rutin in fruit juice under the optimal conditions.

Sensitive and selective detection of carbamazepine in serum samples by bionic double-antibody sandwich method based on cucurbit[7]uril and molecular imprinted polymers.

A novel bionic enzyme-linked immunosorbent assay (BELISA) based on double-antibody sandwich method is firstly designed for the detection of carbamazepine (CBZ) in human serum samples. In this BELISA system, cucurbit[7]uril (CB[7]) is employed as an artificial capture antibody (cAb), and molecularly imprinted polymers (MIPs) is used as an artificial detection antibody (dAb). Nanozymes (PdNPs) as signal generators are integrated with MIPs. This couple of bionic antibodies exhibits not only the excellent physical and chemical stability, but also the superior molecular recognition ability. Based on two bionic antibodies that can selectively recognize different sites of CBZ molecule, a new BELISA method has been constructed for the first time. The proposed BELISA method displays a good linear relationship ranging from 2 to 20 µg mL-1. The detection limit is 0.37 µg mL-1, which can well meet clinical testing demand. It provides a more stable and economical method for clinical therapeutic drug monitoring (TDM).

Simple and Efficient Detection Approach of Quercetin from Biological Matrix by Novel Surface Imprinted Polymer Based Magnetic Halloysite Nanotubes Prepared by a Sol-Gel Method.

Molecular imprinted polymers coated magnetic halloysite nanotubes (MHNTs-MIPs) were prepared through sol-gel method by using quercetin (Que), APTES and TEOS as template, monomer and cross-linker agent, respectively. The synthesized MHNTs-MIPs were characterized by fourier transform infrared, scanning electron microscope, transmission electron microscope, XRD and vibrating sample magnetometer. Various parameters influencing the binding capacity of the MHNTs-MIPs were investigated with the help of response surface methodology. Selectivity experiments showed that the MHNTs-MIPs exhibited the maximum selective rebinding to Que. Therefore, the MHNTs-MIPs was applied as a solid-phase extraction adsorbent for the extraction and preconcentration of quercetin and luteolin in serum and urine samples. The limits of detection for quercetin and luteolin range from 0.51 to 1.32 ng mL-1 in serum and from 0.23 to 1.05 ng mL-1 in urine, the recoveries are between 95.20 and 103.73% with the RSD less than 5.77%. While the recovery hardly decreased after several cycles. The designed MHNTs-MIP with high affinity, sensitivity and maximum selectivity toward Que in SPE might recommend a novel method for the extraction of flavonoids in other samples like natural products.

ZnO nanorods/Fe3O4-graphene oxide/metal-organic framework nanocomposite: recyclable and robust photocatalyst for degradation of pharmaceutical pollutants.

Nanosized semiconductors are widely utilized as solar energy based photocatalyst. However, the deficiencies such as poor adsorption toward contaminants and recyclability issues, rapid recombination of photo-introduced radicals, and deactivation by scavengers are still be the obstacle. To addressing those obstacles, zeolitic imidazolate framework-8 (ZIF-8), photosensitive ZnO, and paramagnetic Fe3O4 were anchored on conductive graphene oxide (GO) to prepare a nanocomposite photocatalyst ZnO/Fe3O4-GO/ZIF. The photocatalyst showed good robustness to scavengers of hydroxyl radicals (OH•), superoxide radicals (O2•-), and hole (h+) with hydrophobic ZIF-8 modified surface. Finally, four pharmaceuticals (sulfamethazine, metronidazole, norfloxacin, and 4-acetaminophen) were degraded rapidly under simulated solar irradiation for 1 h, and the photocatalyst could be recycled at least ten times without obvious deactivation. The final results show that combination of semiconductor, graphene oxide and ZIF-8 is a good idea for construction of efficient photocatalyst. It offers new views in interface modification of nanomaterials, photocatalysis, and adsorption.