Molecularly imprinted graphite spray ionization-ion mobility spectrometry: application to trace analysis of the pesticide propoxur.

A porous graphite sheet modified by a molecularly imprinted polymer (MIP) was directly used as the spray ionization source for ion mobility spectrometry (IMS). Therefore, it was possible to selectively analyze samples extracted by the molecularly imprinted polymer. This obviates the need for the steps of elution, solvent evaporation, dissolution and injection. To prepare the sheet, the graphite surface was first modified by electrodeposition of a molecularly imprinted polypyrrole film. This polypyrrole film was fabricated in a three-electrode electrochemical system using cyclic voltammetry. The electropolymerization of the graphite sheet was carried out with LiClO4 as a supporting electrolyte in the reaction solution. The effects of the amount of monomer, the level of template concentrations, and the time of polymerization on the extraction efficiency of the MIP film were evaluated. The extraction conditions including extraction time, the extraction temperature, the pH values, the salt concentrations, and the stirring rate were also studied. Methanol was selected as the most suitable solvent for both desorption and ionization which occur simultaneously. The pesticide propoxur (acting as a test compound) was extracted from water samples and directly analyzed using IMS. The analytical parameters (working range: 1.0 to 250 ng·mL-1; detection limit: 0.3 ng·mL-1) indicated that the direct coupling of MIP and IMS has a great potential in terms of reproducibility, and speed of the analysis, while maintaining acceptable sensitivity. Graphical abstract Schematic presentation of molecularly imprinted graphite spray ionization coupled with ion mobility spectrometry (IMS) for rapid/selective extraction and ionization: Application to the pre-concentration of propoxur prior to its quantification by IMS.

DNA G-quadruplexes binding and antitumor activity of palladium aryl oxime ligand complexes encapsulated in either albumin or algal cellulose nanoparticles.

The interactions between two Pd complexes, designated as [Pd3(C,N-(C6H4C(Cl) = NO)-4)6] (complex 1) and [Pd3(C12H8C = NO)6] (complex 2), with the human telomeric G-quadruplex DNA, 5'-G3(T2AG3)3-3' (HTG21), were monitored using spectroscopic, biological, and molecular modeling studies. According to the UV-vis results, these complexes can strongly induce and stabilize G-quadruplex DNA structure with Kb1 = 4.5(±0.3) × 106 M-1 and Kb2 = 1.0(±0.2) × 107 M-1via groove mode in comparison with duplex DNA. The release mechanism of the Pd complexes from BSA nanoparticles followed a biphasic pattern unlike that of algal cellulose nanoparticles in vitro. In addition, the cytotoxicity of these complexes on MCF-7 cancer cells and PBMC normal cells was evaluated and compared with cisplatin under similar experimental conditions. Furthermore, to determine and verify the interaction mode of these compounds with G-quadruplex, the molecular docking technique was also performed. Our data clearly demonstrated that complex 2 had higher activity and cytotoxicity than that of complex 1 and could be further investigated in the future as a drug discovery platform.

Porous graphite sheet spray ionization ion mobility spectrometry.

In this work, a porous graphite sheet is introduced as the substrate in a spray ionization source for ion mobility spectrometry (PGSI-IMS) for the first time. This ionization source has some important advantages in comparison with the hollow needle, which is conventionally used in electrospray ionization. In order to prepare the hydrophilic surface needed to load samples on a graphite substrate, the graphite sheet was treated with hot sulfuric acid solution for 2 hours. Some parameters affecting the ionization efficiency were studied, and the optimized conditions were found to be 3.5-kV graphite voltage, 24-µL methanol flow rate, 500 mL min-1 the gas flow rate, and graphite sheet with a 60° tip angle and 3-mm distance from the counter electrode. Finally, analyses of some test compounds (imipramine, diclofenac, codeine, morphine, and ethion) were conducted to evaluate the capability of the new ionization source in the positive and negative modes. The satisfactory results proved the capability of the graphite sheet spray ionization, to be conveniently used for routine analysis of chemical compounds by IMS.

Ingenious pH-sensitive etoposide loaded folic acid decorated mesoporous silica-carbon dot with carboxymethyl-ßcyclodextrin gatekeeper for targeted drug delivery and imaging.

A new strategy is reported for the synthesis of label-free fluorescent mesoporous silica (MS) by the introduction of fluorescent carbon dots in the MSs (MSCDs) in this work. Etoposide (ETO) loaded MSCDs have been used as a drug model. Carboxymethyl ß-cyclodextrin (CßCD) used as a gatekeeper agent was attached to amine-functionalized MSCDs to retain ETO molecules inside the nanocarrier. In order to target the nanocarrier to the site of action, folic acid (FA) was grafted onto the MSCDs surface (FA-CßCD-MSCDs). The in vitro release of an entrapped ETO from the formulation in phosphate buffered saline (PBS) (pH 7.4) and citrate buffer (pH 5.4) was investigated. At neutral pH in PBS, the pores are blocked by CßCD which prevent premature ETO release. However, under the weakly acidic intercellular environment of the tumor, the amide bond can be partially hydrolyzed and consequently lead to the ETO release from the nanocarrier. The targeted and ETO-loaded FA-CßCD-MSCDs showed a higher growth inhibition towards FA-positive HeLa cells compared with FA-negative HepG2 cells, as demonstrated by comparison of in vitro cytotoxicity experiments. In addition, the CDs emission was used for the fluorescent microscopic imaging. Moreover, molecular docking and molecular dynamics simulations (MDS) were applied to examine the interactions of ETO molecules with the topoisomerase II (Top II). ETO molecules bind Top II with overall binding constants of 3.08 × 1010 M-1, according to docking results. Based on MDS results, ETO-Top II complex is formed through hydrophobic interactions.

Aptamer-modified carbon nanomaterial based sorption coupled to paper spray ion mobility spectrometry for highly sensitive and selective determination of methamphetamine.

A cellulose paper was modified with an aptamer against methamphetamine on either carbon dots (CDs) or on multichannel carbon nanotubes (CNTs). The resulting sorbent was applied to the extraction of METH from blood or saliva. The METH-loaded paper than also was directly applied as a paper spray ionization source in ion mobility spectrometry. The carbon nanomaterial enhances sensitivity, and the aptamer enhances selectivity. The materials were covalently bound to the paper on one side, while the aptamer was immobilized on the other. After optimization of the extraction process and instrumental parameters, the limits of detection when using the aptamer-CNT modified paper are 0.6 ng·mL-1 for saliva, and 0.45 ng·mL-1 for plasma. The respective values when using aptamer-CD modified paper are 1.5 ng·mL-1 for saliva and 0.9 ng·mL-1 for plasma. Calibration plots are linear in the 2 to 150 ng·mL-1 METH concentration range for saliva, and in the 1.5 to 200 ng·mL-1 concentration ranges for blood when using the aptamer-CNT based method. When using the aptamer-CDs, the dynamic ranges extend from 5 to 200 ng·mL-1 and from 3 to 250 ng·mL-1, respectively. The method was applied to the determination of METH in real samples of saliva and blood, and the accuracy of the method was confirmed by comparison of the results with data analyzed by GC-MS. Graphical abstract ᅟ.

A fluorescent aptasensor for analysis of adenosine triphosphate based on aptamer-magnetic nanoparticles and its single-stranded complementary DNA labeled carbon dots.

A new fluorimetric aptasensor was designed for the determination of adenosine triphosphate (ATP) based on magnetic nanoparticles (MNPs) and carbon dots (CDs). In this analytical strategy, an ATP aptamer was conjugated on MNPs and a complementary strand of the aptamer (CS) was labeled with CDs. The aptamer and its CS were hybridized to form a double helical structure. The hybridized aptamers could be used for the specific recognition of ATP in a biological complex matrix using a strong magnetic field to remove the interfering effect. In the absence of ATP, no CDs-CS could be released into the solution and this resulted in a weak fluorescence signal. In the presence of ATP, the target binds to its aptamer and causes the dissociation of the double helical structure and liberation of the CS, such that a strong fluorescence signal was generated. The increased fluorescence signal was proportional to ATP concentration. The limit of detection was estimated to be 1.0 pmol L-1 with a dynamic range of 3.0 pmol L-1 to 5.0 nmol L-1 . The specific aptasensor was applied to detect ATP in human serum samples with satisfactory results. Moreover, molecular dynamic simulation (MDS) studies were used to analyze interactions of the ATP molecule with the aptamer.

Folate receptor-targeted multimodal fluorescence mesosilica nanoparticles for imaging, delivery palladium complex and in vitro G-quadruplex DNA interaction.

New folic acid-conjugated mesoporous silica nanoparticles were synthesized. The effect of calcination at 400°C on the fluorescence characteristics of mesoporous silica nanoparticles were studied in this work. The formed carbon dots (CDs) from calcination were used as the source of fluorescence. 3-Aminopropyltriethoxysilane was then used to amine-functionalized the fluorescent surface of mesoporous silica nanoparticles. The amine fluorescence mesoporous silica nanoparticles (amine-FMSNs) were coupled with folic acid (FA) as the target ligand (FA-amine-FMSNs). A palladium complex was also synthesized and encapsulated in the FA-amine-FMSNs yielded fluorescent property with therapeutic effect. The in vitro release of an entrapped palladium complex from FA-amine-FMSNs was studied under physiological conditions. According to the cell viability assay on HeLa (positive FR) and Hep-G2 (negative FR) cells, the targeted delivery system inhibited the growth of positive FR with higher selectivity compared with negative FR cells. Also, the emission CDs were used for fluorescence microscopic imaging. To confirm anti-cancer activity of the palladium complex, the interaction between palladium complex and G-quadruplex DNA were investigated with multi-spectroscopic methods and molecular modeling. The molecular docking studies showed a partial intercalation mode with a 4.27 × 105 M-1 binding constant.

Conical Torch: The Next-Generation Inductively Coupled Plasma Source for Spectrochemical Analysis.

A completely new ICP torch for optical/mass spectrometry is introduced with a conical geometry leading to significant reduction in gas and power consumption. As a new holistic methodology, the torch has been designed on the basis of fluid flow patterns, heat transfer, plasma physics, and analytical performance. Computer simulations, capable of accounting for magneto-hydrodynamic effects, have been used to optimize torch geometry. The result is a "conical" torch with up to 70% reduction in argon flow and more than 4 times power density compared with traditional "cylindrical" torches. Based on experimental measurements, these features lead to a stable plasma with 1000-1700K higher excitation/rotational temperature and a 5-fold increase in electron number density compared to common torches. Interferences from easily ionizable elements (e.g., Na) are also observed to be minimized due to 3 times higher robustness (Mg II/Mg I ratio). Eventually, analytical parameters including detection limits for multielement analysis indicate comparable/better performance of the new torch in comparison with conventional torches.

Immobilized aptamer paper spray ionization source for ion mobility spectrometry.

A selective thin-film microextraction based on aptamer immobilized on cellulose paper was used as a paper spray ionization source for ion mobility spectrometry (PSI-IMS), for the first time. In this method, the paper is not only used as an ionization source but also it is utilized for the selective extraction of analyte, based on immobilized aptamer. This combination integrates both sample preparation and analyte ionization in a Whatman paper. To that end, an appropriate sample introduction system with a novel design was constructed for the paper spray ionization source. Using this system, a continuous solvent flow works as an elution and spray solvent simultaneously. In this method, analyte is adsorbed on a triangular paper with immobilized aptamer and then it is desorbed and ionized by elution solvent and applied high voltage on paper, respectively. The effects of different experimental parameters such as applied voltage, angle of paper tip, distance between paper tip and counter electrode, elution solvent type, and solvent flow rate were optimized. The proposed method was exhaustively validated in terms of sensitivity and reproducibility by analyzing the standard solutions of codeine and acetamiprid. The analytical results obtained are promising enough to ensure the use of immobilized aptamer paper-spray as both the extraction and ionization techniques in IMS for direct analysis of biomedicine.

Aptasensor based on fluorescence resonance energy transfer for the analysis of adenosine in urine samples of lung cancer patients.

A new aptasensor was designed for the analysis of adenosine based on fluorescence resonance energy transfer (FRET) between CdS quantum dot (QDs) as a donor and polypyrrole (Ppy) as an acceptor. The QDs were covalently bonded to anti-adenosine aptamer where its fluorescence was quenched by Ppy. When Ppy was replaced by adenosine, the fluorescence of QDs was restored and its intensity was proportional to the adenosine concentration. Under the optimized conditions, a linear range was found to be 23-146 nM with a detection limit of 9.3 nM. The method was used for analysis of adenosine in urine samples of lung cancer patients and its accuracy was evaluated by comparison of the results of the proposed method with the standard method of HPLC-UV. Furthermore, the interactions of adenosine molecules with the aptamer were investigated using molecular modeling, including molecular dynamic simulations (MDS). The results demonstrated that each G-quadruplex aptamer can capture two adenosine molecules.

Aptamer-conjugated magnetic nanoparticles for extraction of adenosine from urine followed by electrospray ion mobility spectrometry.

Magnetic nanoparticles (MNPs) conjugated with aptamer was developed for the selective extraction of adenosine in urine samples followed by electrospray ionization-ion mobility spectrometry (ESI-IMS). The ion mobility spectrum of adenosine showed two peaks at low concentrations and two more peaks related to dimer of adenosine at high concentrations. However, the ion mobility spectrum of eluent at low concentration showed only the peaks related to dimer of adenosine. In other words, aptamer captured two adenosine molecules between the top G-quartet and the two short stems, where they bonded to each other. The mass spectrum of the eluent also validated the presence of dimer (m/z 535.95). The effect of extraction parameters on extraction efficiency including sorbent amount, elution conditions (solvent type and volume) and adsorption conditions were investigated. Under the optimized conditions, the linear dynamic range was found to be 0.05-5.00 µg mL(-1) with detection limit of 0.02 µg mL(-1). The extraction efficiency was 94% and the relative standard deviation was 4% for three replicate measurements of adenosine at 0.25 µg mL(-1) in urine samples. As a practical application, the method was applied for the determination of adenosine in urine samples of patients with lung cancer, and the obtained results were in good agreement with those obtained by HPLC-UV method. Therefore, the proposed method is an alternative clinical analysis.

Spectroscopic, biological, and molecular modeling studies on the interactions of [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from bovine serum albumin (BSA) nanoparticles.

The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential target of anticancer drugs. In this work, a mononuclear Fe(III) complex containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer. The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'-G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods of UV-vis, fluorescence, and circular dichroism showed that the metal complex can effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex was measured by these methods and it was found to be 4.53(±0.30) × 10(5) M(-1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA amplification. The cell viability assay showed that the complex has significant antitumor activities against Hela cells. According to the UV-vis results, the interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower than G-quadruplex. Furthermore, the release of the complex incorporated in bovine serum albumin nanoparticles was also investigated in physiological conditions. The release of the complex followed a bi-phasic release pattern with high and low releasing rates at the first and second phases, respectively. Also, in order to obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular modeling was performed. The molecular docking results showed that the Fe(III) complex was docked to the end-stacked of the G-quadruplex with a π-π interaction, created between the meloxicam ligand and the guanine bases of the G-quadruplex.

Anticodeine aptamer immobilized on a Whatman cellulose paper for thin-film microextraction of codeine from urine followed by electrospray ionization ion mobility spectrometry.

A combination of thin-film microextaction based on an aptamer immobilized on modified Whatman cellulose paper followed by electrospray ionization ion mobility spectrometry has been developed for the analysis of codeine in urine samples. The immobilization is based on the covalent linking of an amino-modified anticodeine aptamer to aldehyde groups of the oxidized cellulose paper. The covalent bonds were examined by infrared spectroscopy and elemental analysis. The effect of the extraction parameters, including the elution conditions (solvent type and volume), extraction time, and extraction temperature, on the extraction efficiency were investigated. Under the optimized conditions, the linear dynamic range was found to be 10-300 ng/mL with a detection limit of 3.4 ng/mL for codeine in urine. The relative standard deviation was 6.8% for three replicate measurements of codeine at 100 ng/mL in urine. Furthermore, the samples were analyzed with a standard method for the analysis of codeine using high-performance liquid chromatography with ultraviolet detection. The comparison of the results validates the accuracy of the proposed method as an alternative method for the analysis of codeine in urine samples.

A mononuclear zinc(II) complex with piroxicam: crystal structure, DNA- and BSA-binding studies; in vitro cell cytotoxicity and molecular modeling of oxicam complexes.

A new mononuclear Zn(II) complex, trans-[Zn(Pir)2(DMSO)2], where Pir(-) is 4-hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), has been synthesized and characterized. The crystal structure of the complex was obtained by the single crystal X-ray diffraction technique. The interaction of the complex with DNA and BSA was investigated. The complex interacts with FS-DNA by two binding modes, viz., electrostatic and groove binding (major and minor). The microenvironment and the secondary structure of BSA are changed in the presence of the complex. The anticancer effects of the seven complexes of oxicam family were also determined on the human K562 cell lines and the results showed reasonable cytotoxicities. The interactions of the oxicam complexes with BSA and DNA were modeled by molecular docking and molecular dynamic simulation methods.

Experimental and molecular modeling studies of the interaction of the polypyridyl Fe(II) and Fe(III) complexes with DNA and BSA.

Two mononuclear iron complexes, [Fe(tppz)2](PF6)2·H2O (1) and Fe(tppz)Cl3·2CHCl3 (2) where tppz is (2,3,5,6-tetra(2-pyridyl)pyrazine), have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-Vis and IR) and single crystal X-ray structure analysis. The interaction of (1) as the nitrate salt ([Fe(tppz)2](NO3)2) with calf-thymus DNA (CT-DNA) has been monitored by UV-Vis spectroscopy, competitive fluorescence titration, circular dichroism (CD), voltammetric techniques, viscosity measurement, and gel electrophoresis. Gel electrophoresis of DNA with [Fe(tppz)2](NO3)2 demonstrated that the complex also has the ability to cleave supercoiled plasmid DNA. The results have indicated that the complex binds to CT-DNA by three binding modes, viz., electrostatic, groove and partial insertion of the pyridyl rings between the base stacks of double-stranded DNA. Molecular docking of [Fe(tppz)2](NO3)2 with the DNA sequence d(ACCGACGTCGGT)2 suggests the complex fits into the major groove. The water-insoluble complex (2) can catalyze the cleavage of BSA at 40 °C. There are no reports of the catalytic effect of polypyridyl metal complexes on the BSA cleavage. Molecular docking of (2) with BSA suggests that, when the chloro ligands in the axial positions are replaced by water molecules, the BSA can interact with the Fe(III) complex more easily.

Extraction of methocarbamol from human plasma with a polypyrrole/multiwalled carbon nanotubes composite decorated with magnetic nanoparticles as an adsorbent followed by electrospray ionization ion mobility spectrometry detection.

In this work, a polypyrrole/multiwalled carbon nanotubes composite decorated with Fe3 O4 nanoparticles was chemically synthesized and applied as a novel adsorbent for the extraction of methocarbamol from human plasma. Electrospray ionization ion mobility spectrometry was used for the determination of the analyte. The properties of the magnetic-modified adsorbent were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform IR spectroscopy, and X-ray diffraction. The effects of experimental parameters on the extraction efficiency of the sorbent were investigated. Under the optimized conditions, the linear dynamic range was found to be 2-150 ng/mL with the detection limit of 0.9 ng/mL. The relative standard deviation was 5.3% for three replicate measurements of methocarbamol in plasma sample. The extraction efficiency of the sorbent for the determination of different drugs with various polarities was also compared to that of Fe3 O4 -polypyrrole and Fe3 O4 -multiwalled carbon nanotubes sorbents. Finally, the method was used for the determination of methocarbamol in blood samples.

Experimental and molecular modeling studies on the interaction of the Ru(II)-piroxicam with DNA and BSA.

A mononuclear Ru(II) complex containing two piroxicam (Pir(-)) ligands was synthesized and fully characterized. Interaction studies of the Pir(-) anion and the Ru(II) complex with DNA and BSA were carried out using spectroscopic techniques. The results suggested that the Pir(-) anion binds to DNA in a moderately strong fashion via intercalation between the base stacks of double-stranded DNA, while the Ru(II) complex is a groove binder and interacts with DNA with more affinity. Moreover, the results demonstrated that the microenvironment and the secondary structure of BSA were changed in the presence of Pir(‾) and Ru(II) complex. The free Pir(‾) ligand and the Ru(II) complex can lead to the photocleavage of DNA supercoiled pUC57. Finally, the binding of the Ru(II) complex to BSA and DNA was modeled by molecular docking and molecular dynamic simulation methods.

Aptamer based extraction followed by electrospray ionization-ion mobility spectrometry for analysis of tetracycline in biological fluids.

An extraction method based on aptamer sorbent followed by electrospray ionization-ion mobility spectrometry (ESI-IMS) has been developed for the analysis of tetracycline in human urine and plasma samples. The effect of extraction parameters on the extraction efficiency including washing (solvent type and volume) and elution (solvent type, volume and flow rate) were investigated. Under the optimized conditions, the linear dynamic ranges for tetracycline in urine and plasma samples were found to be 0.05-5.00 µg/mL and 0.10-5.00 µg/mL with detection limits of 0.019 and 0.037 µg/mL, respectively. The extraction efficiency was 86.5% for urine and it was 82.8% for plasma samples. The relative standard deviation was 5.9% and 6.3% for six replicate measurements of tetracycline at 1 and 2 µg/mL in urine and plasma samples, respectively.

A chemiluminescent metalloimmunoassay based on copper-enhanced gold nanoparticles for quantification of human growth hormone.

A chemiluminescence (CL) immunoassay was developed to determine human growth hormone (hGH) based on copper-enhanced gold nanoparticles. In this method, gold nanoparticles were deposited on polystyrene wells for adsorption of human growth antibodies as well as catalyst for reducing of copper ions from the copper enhancer solution. The reduction of copper ions was prevented where the gold nanoparticles were covered by the antibody-antigen immunocomplex. The deposited copper on Au nanoparticles was then dissolved in HNO3 solution and quantified using the CL method. The CL intensity response was logarithmically dependent on the hGH concentrations over the range 0.2-50 ng/mL, with a detection limit (3σ) of 0.036 ng/mL.

Investigation of the interaction between amodiaquine and human serum albumin by fluorescence spectroscopy and molecular modeling.

The interaction of amodiaquine (AQ) with human serum albumin (HSA) has been studied by fluorescence spectroscopy. Based on the sign and magnitude of the enthalpy and entropy changes (ΔH(0) = -43.27 kJ mol(-1) and ΔS(0) = -50.03 J mol(-1) K(-1)), hydrogen bond and van der Waals forces were suggested as the main interacting forces. Moreover, the efficiency of energy transfer and distance between HSA and acceptor AQ was calculated. Finally, the binding of AQ to HSA was modeled by molecular docking and molecular dynamic simulation methods. Excellent agreement was found between the experimental and theoretical results. Both experimental results and modeling methods suggested that AQ binds mainly to the sub-domain IIA of HSA.