Semi-Empirical Topological Method for Prediction of the Relative Retention Time of Polychlorinated Biphenyl Congeners on 18 Different HR GC Columns

High resolution gas chromatographic relative retention time (HRGC-RRT) models were developed to predict relative retention times of the 209 individual polychlorinated biphenyls (PCBs) congeners. To estimate and predict the HRGC-RRT values of all PCBs on 18 different stationary phases, a multiple linear regression equation of the form RRT = ao + a1 (no. o-Cl) + a2 (no. m-Cl) + a3 (no. p-Cl) + a4 (VM or SM) was used. Molecular descriptors in the models included the number of ortho-, meta-, and para-chlorine substituents (no. o-Cl, m-Cl and p-Cl, respectively), the semi-empirically calculated molecular volume (VM), and the molecular surface area (SM). By means of the final variable selection method, four optimal semi-empirical descriptors were selected to develop a QSRR model for the prediction of RRT in PCBs with a correlation coefficient between 0.9272 and 0.9928 and a leave-one-out cross-validation correlation coefficient between 0.9230 and 0.9924 on each stationary phase. The root mean squares errors over different 18 stationary phases are within the range of 0.0108–0.0335. The accuracy of all the developed models were investigated using cross-validation leave-one-out (LOO), Y-randomization, external validation through an odd–even number and division of the entire data set into training and test sets

Molecular docking and CoMFA studies of thiazoloquin(az)olin(on)es as CD38 inhibitors: determination of inhibitory mechanism, pharmacophore interactions, and design of new inhibitors

<p>In this research, molecular docking and 3D-QSAR studies were carried out on a series of 79 thiazoloquin(az)olin(on)es as CD38 inhibitors. Based on docking results, four interactions including hydrogen bonding with main chain of GLU-226 (H-M-GLU-226), Van der Waals interactions with side chain of TRP-125 (V-S-TRP-125), TRP-189 (V-S-TRP-189), and THR-221 (V-S-THR-221) were considered as pharmacological interactions. Active conformation of each ligand was extracted from docking studies and was used for carrying out 3D-QSAR modeling. Comparative molecular field analysis (CoMFA) was performed on CD38 inhibitory activities of these compounds on human and mouse. We developed CoMFA models with five components as optimum models for both data-sets. For human data-set, a model with high predictive power was developed. <i>R</i>², RMSE, and <i>F</i>-test values for training set of this model were .94, .24, and 179.58, respectively, and <i>R</i>² and RMSE for its test set were .92 and .32, respectively. The <i>q</i>² and RMSE values for leave-one-out cross validation test on training set were .78 and .46, respectively, that demonstrate created model is robust. Based on extracted steric and electrostatic contour maps for this model, three inhibitors with pIC₅₀ larger than 8.85 were designed.</p

Optimization of Auxiliary Solvent Demulsification Microextraction for Determination of Cyanide in Environmental Water and Biological Samples by Microvolume UV-Vis Spectrophotometry

A new, simple, rapid and efficient solvent terminated-auxiliary solvent-dispersive liquid-liquid microextraction (ST-AS-DLLME) technique for determination of cyanide ions by microvolume UV-Vis spectrophotometry was developed. Effective parameters on the extraction and absorbance of cyanide were optimized using two optimization methods: fractional factorial design (FFD) and central composite design (CCD). Zinc(II) tetraphenylporphyrine (ZnTPP) was used as a selective cyanide receptor agent. Methyl isobutyl ketone (MIBK), ethanol and 1-butanol were used as extraction solvent, dispersive solvent and demulsifier solvent, respectively. The method shows very good selectivity in presence of other species. The analytical curve was linear in the range of 4.0-130 &#181;g L-1 with a limit of detection of 1.0 &#181;g L-1. Relative standard deviation (RSD) of the method for ten replicate measurements of 100 &#181;g L-1 of cyanide was 1.1%. The method was successfully applied for determination of cyanide in natural water and plasma samples with good spike recoveries