Molecular dynamics simulation study and molecular docking descriptors in structure-based QSAR on acetylcholinesterase (AChE) inhibitors.

In this study we present an approach for predicting the inhibitory activity of acetylcholinesterase (AChE) inhibitors by combining molecular dynamics (MD) simulation and docking studies in a structure-based quantitative structure-activity relationship (QSAR) model. The MD simulation was performed on AChE to obtain enzyme conformation in a water environment. The resulting conformation of the enzyme was used for docking with the most potent inhibitor (26a). Docking analysis revealed that hydrophobic interactions play important roles in the AChE-inhibitor complex. Then, all inhibitors that could bind simultaneously at the catalytic site and at the peripheral anionic site of AChE were docked into the enzyme and their interactions with AChE were used as new interpretable descriptors in a structure-based QSAR model. The least squares support vector regression was constructed using the four most relevant docking descriptors and one molecular structure descriptor. The Q(2) value of the model was found to be 0.790. Furthermore, to study the enzyme conformation stability, a second MD simulation was performed on AChE-inhibitor 26a complex. In MD simulation, the topological parameters of the inhibitor were derived from the PRODRG server, and partial atomic charges were modified using the B3LYP/6-31G level of theory. The radius of gyration for the complex showed that AChE conformation did not change in the presence of the inhibitors.

Direct coupling of packed column supercritical fluid chromatography to continuous corona discharge ion mobility spectrometry.

In this study, packed column supercritical fluid chromatography (SFC) was directly coupled to a continuous corona discharge (CD) ion mobility spectrometer (IMS) with several modifications. The main advantage of the developed detector is its capability to introduce full column effluent up to 2000 mL min(-1) CO(2) gas directly into the IMS cell relative to 40 mL min(-1) CO(2) gas as a maximum tolerance, reported for the previous IMS detectors. This achievement was made possible because of using corona discharge instead of (63)Ni as an ionization source and locating the inlet and outlet of the CO(2) gas in the counter electrode of the CD in opposite direction. In addition, a heated interface was placed between back pressure regulator (BPR) and the IMS cell to heat the output of the BPR for introducing sample as the gas phase into the IMS cell. Furthermore, a make-up methanol flow was introduced between the column outlet and BPR to provide a more uniform flow through the BPR and also to prevent freezing and deposition of the analytes in the BPR. The performance of the SFC-CD-IMS was evaluated by analysis of testosterone, medroxyprogesterone, caffeine, and theophylline as test compounds and figures of merit for these compounds have been calculated.

Pneumatically assisted electrospray-ion mobility spectrometry for quantitative analysis of intact proteins.

In this work, quantitative analysis of intact proteins using ion mobility spectrometry (IMS) is introduced. For this purpose a pneumatically assisted electrospray ionization source with a new design was constructed. Liquid and nebulizer gas flow rates were optimized to achieve the highest response. The pneumatically assisted electrospray-IMS was used for quantitative analysis of insulin, bovine serum albumin (BSA) and human serum albumin (HSA). The analysis of proteins demonstrated that sensitivity of the pneumatically assisted electrospray-IMS is two to three times higher than that of conventional electrospray ionization (ESI) coupled to IMS. The linear dynamic ranges for insulin, BSA and HSA were found to be 1-75, 5-100 and 2-100 µg mL(-1) with detection limits of 0.3, 1 and 0.6 µg mL(-1), respectively. The relative standard deviations (RSD) for five replicate measurements of insulin, BSA, and HSA at 25 µg mL(-1) were recorded as 3, 4 and 1.5%, respectively. The proposed method can be considered as an alternative way for quantitative protein analysis.

Design and construct of a new detector for gas chromatography based on continuous negative corona discharge.

In this work, a new detector was designed and constructed based on negative corona discharge. This detector can be used separately or as a detector in gas chromatography. The detector and chromatographic variables including cell temperature, gas flow rates, voltage between the two electrodes, and column temperature were optimized. Chloroform was used as a test compound to evaluate the performance of the detector. The detection limit of chloroform was obtained 0.78 ng∕ml and its dynamic range was over the range of 2-840 ng∕ml. The relative standard detection was about 6% for the limit of quantification. This detector is able to be used as an alternative for analysis of compounds containing electronegative elements.

Simultaneous chemiluminescence determination of amoxicillin and clavulanic acid using least squares support vector regression.

In this work, both the batch and flow injection chemiluminescence (CL) methods have been proposed for the simultaneous determination of two structurally similar beta-lactams including amoxicillin and clavulanic acid (CLAV). Chemiluminescence spectral overlap of these two structurally similar beta-lactams is the main limitation for the simultaneous analysis of the two compounds. Least squares support vector regression (LS-SVR) was applied to relate concentration of both the compounds to their CL profiles. The parameters of the model, consisting of kernel parameter, sigma(2), and the regularization parameter, gamma, were optimized by constructing different LS-SVR models and the model with the minimum root mean squared error of cross-validation (RMSECV) for the calibration set was selected as the best model and its parameters were chosen as the optimized values. The performance of LS-SVR model was compared with Partial Least Squares (PLS) and the results revealed the superiority of the LS-SVR over PLS model. Under the optimized experimental conditions for both the compounds, when LS-SVR was applied, the detection limits obtained were 0.2 and 0.60 micromol L(-1) in the batch mode and 0.3 and 0.5 micromol L(-1) in the flow injection mode for CLAV and amoxicillin, respectively. The proposed method was utilized for the simultaneous determination of the compounds in pharmaceutical formulations and spiked plasma samples.

Simultaneous voltammetric determination of enrofloxacin and ciprofloxacin in urine and plasma using multiwall carbon nanotubes modified glassy carbon electrode by least-squares support vector machines.

A simple and sensitive method is proposed for the electrochemical determination of enrofloxacin (ENRO) and its primary metabolite ciprofloxacin (CIPRO) at a multiwall carbon nanotubes/glassy carbon electrode (MWCNT/GCE) using a least-squares support vector machine (LS-SVM) and linear sweep voltammetry. Simultaneous determination of ENRO and CIPRO at bare glassy carbon is associated with certain difficulties due to voltammogram overlapping and their low sensitivity. The resolution of the mixture was carried out using LS-SVM as a multivariate calibration method. Under the optimum conditions at pH 7.0, the linear sweep currents increased linearly with ENRO and CIPRO concentrations in ranges of 2.0-780.0 micromol L(-1) (0.7-280.3 microg mL(-1)) and 3.0-1200 micromol L(-1) (1.0-397.7 microg mL(-1)), respectively. The detection limits for ENRO and CIPRO were 0.5 and 0.9 micromol L(-1), respectively. The proposed method was applied to simultaneously determine both compounds in human urine, plasma and in pharmaceutical samples.

Simultaneous determination of ascorbic acid, epinephrine, and uric acid by differential pulse voltammetry using poly(p-xylenolsulfonephthalein) modified glassy carbon electrode.

A novel poly(p-xylenolsulfonephthalein) modified glassy carbon electrode was prepared for the simultaneous determination of ascorbic acid (AA), epinephrine (EP) and uric acid (UA). Cyclic voltammetric, chronoamperometric, and differential pulse voltammetric methods were used to investigate the modified electrode for the electrocatalytic oxidation of EP, AA, and UA in aqueous solutions. The separation of the oxidation peak potentials for AA-EP and EP-UA was about 200 and 130 mV, respectively. The calibration curves obtained for AA, EP, and UA were in the ranges of 10-1343, 2-390, and 0.1-560 micromol L(-1), respectively. The detection limits (S/N=3) were 4, 0.1, and 0.08 micromol L(-1) for AA, EP and UA, respectively. The diffusion coefficient and the catalytic rate constant for the oxidation of EP at the modified electrode were calculated as 1.40(+/-0.10) x 10(-4) cm(2) s(-1) and 1.06 x 10(3) mol(-1) Ls(-1), respectively. The present method was applied to the determination of EP in pharmaceutical and urine samples, AA in commercially available vitamin C tablet, and EP plus UA in urine samples.

Analysis of biogenic amines using corona discharge ion mobility spectrometry.

A new method based on corona discharge ion mobility spectrometry (CD-IMS) was developed for the analysis of biogenic amines including spermidine, spermine, putrescine, and cadaverine. The ion mobility spectra of the compounds were obtained with and without n-Nonylamine used as the reagent gas. The high proton affinity of n-Nonylamine prevented ion formation from compounds with a proton affinity lower than that of n-Nonylamine and, therefore, enhanced its selectivity. It was also realized that the ion mobility spectrum of n-Nonylamine varied with its concentration. A sample injection port of a gas chromatograph was modified and used as the sample introduction system into the CD-IMS. The detection limits, dynamic ranges, and analytical parameters of the compounds with and without using the reagent gas were obtained. The detection limits and dynamic ranges of the compounds were about 2ng and 2 orders of magnitude, respectively. The wide dynamic range of CD-IMS originates from the high current of the corona discharge. The results revealed the high capability of the CD-IMS for the analysis of biogenic amines.

Simultaneous chemiluminescence determination of thebaine and noscapine using support vector machine regression.

In this work, a batch chemiluminescence (CL) method has been proposed for the simultaneous determination of two structurally similar alkaloids, noscapine and thebaine. The method is based on the kinetic distinction of the CL reactions of noscapine and thebaine with Ru(bipy)(3)(2+) and Ce(IV) system in a sulfuric acid medium. The least squared support vector machine (LS-SVM) regression was applied for relating the concentrations of both compounds to their CL profiles. The parameters of the model consisting of sigma(2) and gamma were optimized by constructing LS-SVM models with all possible combinations of these two parameters to select the model with the minimum root mean squared error of cross validation (RMSECV) as the best. The parameters of this model were then selected as optimized values. Under the optimized experimental conditions for both compounds, the detection limits obtained using the LS-SVM regression were 0.08 and 0.1 micromo lL(-1) for noscapine and thebaine, respectively. The proposed method was utilized for the simultaneous determination of the compounds in pharmaceutical formulations and plasma samples with satisfactory results.

Simultaneous chemiluminescence determination of promazine and fluphenazine using support vector regression.

In this work, chemiluminescence (CL) behaviors of two selected phenothiazines, namely promazine and fluphenazine hydrochloride, were investigated for their simultaneous determination using oxidation of Ru(bipy)(3)(2+) by Ce(4+) ions in acidic media. This method is based on the kinetic distinction of the CL reactions of fluphenazine and promazine with Ru(bipy)(3)(2+) and Ce(4+) system in a sulfuric acid medium. Least square support vector regression models were constructed for relating concentrations of both compounds to their CL profiles. The parameters of the model consisting of sigma(2) and gamma were optimized using all possible combinations of sigma(2) and gamma to select the model with the minimum root mean square cross validation. Under optimized conditions, the univariate calibration curve was linear over the concentration ranges of 0.4-30.0 microg mL(-1) and 0.07-5.0 microg mL(-1) with detection limits of 0.1 microg mL(-1) and 0.04 microg mL(-1) for promazine and fluphenazine, respectively. The influence of potential interfering substances on the determination of promazine and fluphenazine were studied. The proposed method was used for simultaneous determination of both compounds in synthetic mixtures and in spiked human plasma.

Simultaneous determination of 2-furfural and 5-methyl-2-furfural using corona discharge ion mobility spectrometry.

A novel technique, corona discharge ion mobility spectrometry (CD-IMS), was developed for the qualitative and quantitative determination of 2-furfural (F) and 5-methyl-2-furfural (MF) in aqueous solutions. The limits of detection (LODs) were 5.3 x 10(-3) microg/mL for F and 6.7 x 10(-3) microg/mL for MF. The linear dynamic ranges of 1.16 x 10(-2) to 1.04 microg/mL and 2.20 x 10(-2) to 1.10 microg/mL were obtained for F and MF, respectively. The relative standard deviation was below 12% for both compounds. In addition to analysis of the individual compound, simultaneous determination of F and MF was also investigated. It was realized that F imposes a matrix effect on the MF signal and vice versa. The standard addition method was used to deal with the matrix effect. The recovery of the compounds in the synthetic samples validates the capability of the method.

Determination of ultra trace amount of enrofloxacin by adsorptive cathodic stripping voltammetry using copper(II) as an intermediate.

In this work, a simple and sensitive electroanalytical method was developed for the determination of enrofloxacin (ENRO) by adsorptive cathodic stripping voltammetry (ADSV) using Cu(II) as a suitable probe. The complex of copper(II) with ENRO was accumulated at the surface of a hanging mercury drop electrode at -0.10 V for 40 s. Then, the preconcentrated complex was reduced and the peak current was measured using square wave voltammetry (SWV). The optimization of experimental variables was conducted by experimental design and support vector machine (SVM) modeling. The model was used to find optimized values for the factors such as pH, Cu(II) concentration and accumulation potential. Under the optimized conditions, the peak current at -0.30 V is proportional to the concentration of ENRO over the range of 10.0-80.0 nmol L(-1) with a detection limit of 0.33 nmol L(-1). The influence of potential interfering substances on the determination of ENRO was examined. The method was successfully applied to determination of ENRO in plasma and pharmaceutical samples.

Simultaneous determination of codeine and noscapine by flow-injection chemiluminescence method using N-PLS regression.

A flow injection chemiluminescent (FI-CL) method has been developed for the simultaneous determination of codeine and noscapine using N-PLS regression. The method is based on the fact that kinetic characteristics of codeine and noscapine are different in the Ru(phen)(3)(2+)-Ce(IV) CL system. In flow injection mode, codeine gives broad peak with the highest CL intensity at 4.4s, whereas the maximum CL intensity of the noscapine appears at about 2.6s. Moreover, the effect of increasing H(2)SO(4) concentration was different on the CL intensity of the compounds. An experimental design, central composite design (CCD), was used to realize the optimized variables such as Ru(II) and Ce(IV) concentrations for the both compounds. At the optimized condition, a three-way data structure (samples, H(2)SO(4) concentration, time) was constructed and followed by N-PLS regression. The number of factors for the N-PLS regression was selected based on the minimum values for the root mean squared error of cross validation (RMSECV). The proposed method is applied to the simultaneous quantification of codeine and noscapine in the pharmaceutical preparations.

Direct determination of ammoniacal nitrogen in water samples using corona discharge ion mobility spectrometry.

In this study, direct determination of ammoniacal nitrogen residues in water samples using corona discharge ion mobility spectrometry (CD-IMS) was investigated. Pyridine was used as an alternate reagent gas to enhance selectivity and sensitivity of the method. The results indicate that the limit of detection (LOD) was about 9.2x10(-3)mugmL(-1) and the linear dynamic range was obtained from 0.03 to 2.00mugmL(-1). The relative standard deviation was about 11%. Furthermore, this method was successfully applied to the direct determination of ammoniacal nitrogen in river and tap water samples and the results were compared with the Nessler method. The comparison of the results validates the potential of the proposed method as an alternative technique for the analysis of the ammoniacal nitrogen in water samples.

Determination of glutathione in hemolysed erythrocyte by flow injection analysis with chemiluminescence detection.

In this work, a new sensitive method is introduced for analysis of glutathione at trace levels in blood samples. The method is based on the effect of glutathione on the chemiluminescence signal of the oxidation of luminol by sodium periodate in basic solution. The influence of chemical and manifold variables on the sensitivity was studied. At the optimized conditions, the linear range for the determination of glutathione was 1.0x10(-8) to 1.0x10(-5) mol L(-1) with the detection limit (3sigma) of 8x10(-9) mol L(-1). The relative standard deviation for 10 repeated measurements of 1.0x10(-6) mol L(-1) of glutathione was 4%. The results of the method were compared with the Ellman reference method and no significant difference was found. The influence of potential interference substances on the determination of glutathione was studied. The proposed method was applied successfully for the determination of glutathione in real samples such as erythrocyte hemolysed in normal subjects and diabetes.

Design for electrospray ionization-ion mobility spectrometry.

In this study, a new design for electrospray ionization ion mobility spectrometry (ESI-IMS) was developed. This design has two important differences in comparison to the present ESI-IMS systems. First, a few centimeters of the cell comprising the electrospray needle was located outside of the oven used for heating the IMS cell. This modification prevents prespray solvent evaporation problems such as needle clogging and disturbance of the electrospray process. Second, in addition to the drift gas, a counterflow of a heated gas (desolvation gas) was used between the counter electrode and the ion gate to speed up the desolvation process (Hill, H. H., Jr. Anal. Chem. 1998, 70, 4929-4938). This modification increased the solvent evaporation and resulted in decreasing the drift time, increasing the peak intensity and increasing the resolving power (RP) or enhancing the resolution for separation of two adjacent ion peaks. In this work, the ion mobility spectra of different compounds including ethion, malathion, metalaxyl, fenamifos, methylamine, triethylamine, tributhylamine, codeine, and morphine were obtained to confirm enhancing of the resolving power of the ion peaks by using the desolvation gas. Furthermore, the method has also been applied to obtain the figures of merit for ethion as a test compound. The linear dynamic range for ethion was in the range 50-1000 microg/L with a limit of quantification of the 50 microg/L.

Determination of veterinary drug residues in chicken meat using corona discharge ion mobility spectrometry.

A positive corona discharge ion mobility spectrometry (CD-IMS) has been evaluated for the determination of three residual veterinary drugs including furazolidone (FUR), chloramphenicol (CAP), and enrofloxacin (ENR) in poultry for the first time. Pretreatment included extraction of the drugs from samples and further treatment of the extracts by solid phase extraction (SPE) using C(18) sorbents. The limits of quantification (LOQs) were less than 20 microg kg(-1) for all compounds. The calibration plots for these compounds were linear to about three orders of magnitude. The validity of the method was demonstrated by the analysis of spiked and real samples.

Determination of bismuth and copper using adsorptive stripping voltammetry couple with continuous wavelet transform.

A new method is proposed for the determination of bismuth and copper in the presence of each other based on adsorptive stripping voltammetry of complexes of Bi(III)-chromazorul-S and Cu(II)-chromazorul-S at a hanging mercury drop electrode (HMDE). Copper is an interfering element for the determination of Bi(III) because, the voltammograms of Bi(III) and Cu(II) overlapped with each other. Continuous wavelet transform (CWT) was applied to separate the voltammograms. In this regards, wavelet filter, resolution of the peaks and the fitness were optimized to obtain minimum detection limit for the elements. Through continuous wavelet transform Symlet4 (Sym4) wavelet filter at dilation 6, quantitative and qualitative analysis the mixture solutions of bismuth and copper was performed. It was also realized that copper imposes a matrix effect on the determination of Bi(III) and the standard addition method was able to cope with this effect. Bismuth does not have matrix effect on copper determination, therefore, the calibration curve using wavelet coefficients of CWT was used for determination of Cu(II) in the presence of Bi(III). The detection limits were 0.10 and 0.05ngml(-1) for bismuth and copper, respectively. The linear dynamic range of 0.1-30.0 and 0.1-32.0ngml(-1) were obtained for determination of bismuth in the presence of 24.0ngml(-1) of copper and copper in the presence of 24.0ngml(-1) of bismuth, respectively. The method was used for determination of these two cations in water and human hair samples. The results indicate the ability of method for the determination of these two elements in real samples.

Simultaneous kinetic determination of thiocyanate and sulfide using eigenvalue ranking and correlation ranking in principal component-wavelet neural network.

In this work, two toxic compound, sulfide and thiocyanate were determined simultaneously using kinetic spectrophotometry. These anions have shown the catalytic effects on the reaction between iodine and azide. Since the system was nonlinear, a nonlinear model, principal component-wavelet neural network (PC-WNN) was used as the multivariate calibration method. The principal component analysis was used to decrease the dimension of the original matrix. In other words, the scores of the PCs, 5, instead of the original variables, 301, were used as the input for the model. Two methods were used to select the most relevant principal components: eigenvalue ranking and correlation ranking. In this work, eigenvalue and correlation ranking methods have shown better results for thiocyanate and sulfide, respectively, and it can be concluded that these methods are complementary. The WNN has several advantages relative to other types of neural network such as better convergence ability. The data set was divided to calibration, prediction and validation sets. Each set was selected so that the concentrations of the analytes were approximately covered the entire ranges of the analytes. Mean relative error for thiocyanate and sulfide in validation set were 8.5 and 10.6, respectively. Thiocyanate and sulfide can be determined in the range of 60-700ng ml(-1) and 20-400ng ml(-1), respectively. The proposed method was applied for the determination of sulfide and thiocyanate in real samples such as tap, waste and river waters with satisfactory results.

Wavelet neural network modeling in QSPR for prediction of solubility of 25 anthraquinone dyes at different temperatures and pressures in supercritical carbon dioxide.

A wavelet neural network (WNN) model in quantitative structure property relationship (QSPR) was developed for predicting solubility of 25 anthraquinone dyes in supercritical carbon dioxide over a wide range of pressures (70-770 bar) and temperatures (291-423 K). A large number of descriptors were calculated with Dragon software and a subset of calculated descriptors was selected from 18 classes of Dragon descriptors with a stepwise multiple linear regression (MLR) as a feature selection technique. Six calculated and two experimental descriptors, pressure and temperature, were selected as the most feasible descriptors. The selected descriptors were used as input nodes in a wavelet neural network (WNN) model. The wavelet neural network architecture and its parameters were optimized simultaneously. The data was randomly divided to the training, prediction and validation sets. The predictive ability of the model was evaluated using validation data set. The root mean squares error (RMSE) and mean absolute errors were 0.339 and 0.221, respectively, for the validation data set. The performance of the WNN model was also compared with artificial neural network (ANN) model and the results showed the superiority of the WNN over ANN model.