Reza Aalizadeh

Extended Suspect and Non-Target Strategies to Characterize Emerging Polar Organic Contaminants in Raw Wastewater with LC-HRMS/MS.

An integrated workflow based on liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer (LC-QTOF-MS) was developed and applied to detect and identify suspect and unknown contaminants in Greek wastewater. Tentative identifications were initially based on mass accuracy, isotopic pattern, plausibility of the chromatographic retention time and MS/MS spectral interpretation (comparison with spectral libraries, in silico fragmentation). Moreover, new specific strategies for the identification of metabolites were applied to obtain extra confidence including the comparison of diurnal and/or weekly concentration trends of the metabolite and parent compounds and the complementary use of HILIC. Thirteen of 284 predicted and literature metabolites of selected pharmaceuticals and nicotine were tentatively identified in influent samples from Athens and seven were finally confirmed with reference standards. Thirty four nontarget compounds were tentatively identified, four were also confirmed. The sulfonated surfactant diglycol ether sulfate was identified along with others in the homologous series (SO4C2H4(OC2H4)xOH), which have not been previously reported in wastewater. As many surfactants were originally found as nontargets, these compounds were studied in detail through retrospective analysis.

2D and 3D quantitative structure-activity relationship study of hepatitis C virus NS5B polymerase inhibitors by comparative molecular field analysis and comparative molecular similarity indices analysis methods.

In this present study, three-dimensional quantitative structure–activity relationship (3D-QSAR) and 2D-QSAR analyses were performed on the series of compounds Hepatitis C Virus NS5B polymerase inhibitors using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and stepwise multiple linear regression (SW-MLR) approaches. A CoMFA model with good predictive ability was generated based on training set of 39 compounds and showed satisfactory statistical results (q2= 0.600, r2 = 0.871). To improve the contribution of points for next analyses, CoMFA (after region focusing) was employed in biases of similar alignment and showed appropriate predictive results (q2 = 0.691, r2 = 0.889). A reliable CoMSIA model out of 31 different combinations with the higher “leave-one-out’” cross-validation correlation coefficients (q2) were obtained and indicated suitable statistical results (q2 = 0.664, r2 = 0.911). An external test set of nine compounds were used to evaluate...

UHPLC-QTOF MS screening of pharmaceuticals and their metabolites in treated wastewater samples from Athens.

After consumption, pharmaceuticals are excreted as parent compounds and/or metabolites in urine and faeces. Some are not completely removed during wastewater treatments, forcing sewage treatment plants (STPs) to apply alternative technologies to guarantee quality of treated water. To monitor the removal efficiency of STPs, not only unchanged compounds and metabolites have to be taken into account, but also formation of possible transformation products (TPs). In this work, QTOF MS has been used for screening metabolites/TPs of pharmaceuticals in effluent wastewater from Athens. A customised database was built with the exact masses of metabolites reported in literature for the parent drugs found in an initial screening. Additionally, TPs identified in previous degradation experiments performed at our laboratory were included. Up to 34 metabolites/TPs were detected for omeprazole, venlafaxine, clindamycin, clarithromycin, clopidogrel or dipyrone, among others. Seven corresponded to TPs whose reference standards were available at our lab, seven were TPs previously identified in laboratory degradation experiments, eight were TPs tentatively identified by QTOF MS without reference standards, and twelve TPs were discovered after using the common fragmentation pathway approach. Tentative identification of TPs was supported by prediction of their chromatographic retention time based on the use of advanced chemometric QSRR models.

Quantitative Structure–Retention Relationship Models To Support Nontarget High-Resolution Mass Spectrometric Screening of Emerging Contaminants in Environmental Samples

Over the past decade, the application of liquid chromatography-high resolution mass spectroscopy (LC-HRMS) has been growing extensively due to its ability to analyze a wide range of suspected and unknown compounds in environmental samples. However, various criteria, such as mass accuracy and isotopic pattern of the precursor ion, MS/MS spectra evaluation, and retention time plausibility, should be met to reach a certain identification confidence. In this context, a comprehensive workflow based on computational tools was developed to understand the retention time behavior of a large number of compounds belonging to emerging contaminants. Two extensive data sets were built for two chromatographic systems, one for positive and one for negative electrospray ionization mode, containing information for the retention time of 528 and 298 compounds, respectively, to expand the applicability domain of the developed models. Then, the data sets were split into training and test set, employing k-nearest neighborhood c...

Ozonation of ranitidine: Effect of experimental parameters and identification of transformation products.

This study focuses on the effect of experimental parameters on the removal of ranitidine (RAN) during ozonation and the identification of the formed transformation products (TPs). The influence of pH value, the initial concentrations, the inorganic and the organic matter on RANs removal were evaluated. Results indicated high reactivity of RAN with molecular aqueous ozone. Initial ozone concentration and pH were proven the major process parameters. Alkaline pH values promoted degradation and overall mineralization. Dissolved organic matter reacts competitively to RAN with the oxidants (ozone and/or radicals), influencing the target compounds removal. The presence of inorganic ions in the matrix did not seem to affect RAN ozonation. A total of eleven TPs were identified and structurally elucidated, with the complementary use of both Reversed Phase (RP) and Hydrophilic Interaction Liquid Chromatography (HILIC) quadrupole time of flight tandem mass spectrometry (Q-ToF-MS/MS). Most of the TPs (TP-304, TP-315b, TP-299b, TP-333, TP-283) were generated by the attack of ozone at the double bond or the adjacent secondary amine, with the abstraction of NO2 moiety, forming TPs with an aldehyde group and an imine bond. Oxidized derivatives with a carboxylic group (TP-315a, TP-331a, TP-331b, TP-299a) were also formed. RAN S-oxide was identified as an ozonation TP (TP-330) and its structure was confirmed through the analysis of a reference standard. TP-214 was also produced during ozonation, through the CN bond rupture adjacent to the NO2 moiety. HILIC was used complementary to RP, either for the separation and identification of TPs with isomeric structures that may have been co-eluted in RPLC or for the detection of new TPs that were not eluted in the RP chromatographic system. Retention time prediction was used as a supporting tool for the identification of TPs and results were in accordance with the experimental ones in both RP and HILIC.

Analysis of B-Raf^{\mathrm{V600E}} inhibitors using 2D and 3D-QSAR, molecular docking and pharmacophore studies

In the present work, a molecular modeling study was carried out using 2D and 3D quantitative structure-activity relationships for the various series of compounds known as B-Raf

3D-QSAR and molecular docking study of LRRK2 kinase inhibitors by CoMFA and CoMSIA methods.

^{\mathrm{V600E}}

QSAR study of HCV NS5B polymerase inhibitors using the genetic algorithm-multiple linear regression (GA-MLR).

V600E inhibitors. For 2D-QSAR analysis, a linear model was developed by MLR based on GA-OLS with appropriate results