Occurrence and risk evaluation of endocrine-disrupting chemicals in wastewater and surface water of Lahore, Pakistan.

The current study highlights the occurrence, spatial distribution, and risk assessment of 16 endocrine-disrupting chemicals (EDCs) including their transformation products (TPs) in the wastewater and surface water of Lahore, Pakistan, using solid-phase extraction followed by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The parent EDCs include bisphenol A (BPA), triclosan (TCS), triclocarban (TCC), estrone (E1), estradiol (E2), estriol (E3), ethinylestradiol (EE2), 4-n-octylphenol (4n-OP), and 4-n-nonylphenol (4n-NP). The TPs include two TPs each of BPA, TCC, and estrogens along with a TP of TCS. Most EDCs showed 100% detection frequency in the wastewater with highest median concentration of 1310 ng/L for E3. In the surface water, the highest median concentration was, however, observed for BPA (54.6 ng/L). Spatial variations in terms of sum of concentration due to all EDCs and their TPs were observed at different sampling points which suggest contamination due to industrial waste from nearby industrial estate. Risk evaluation in terms of risk quotient (RQ) and estradiol equivalent factor (EEQ) showed that most of EDCs and their TPs could pose high risk and estrogenicity to the surrounding environment. From the results of the current study, it is observed that the environment of Pakistan is deteriorating and is potential risk for endocrine disruption. It is, therefore, recommended to take stringent measures to make it sustainable for current as well as for future generations.

New organosulfur metallic compounds as potent drugs: synthesis, molecular modeling, spectral, antimicrobial, drug likeness and DFT analysis.

During the present investigation, two new sulfonamide-based Schiff base ligands, 4-{[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L1) and 4-{[1-(2-hydroxyphenyl)ethylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L2), have been synthesized and coordinated with the transition metals (V, Fe, Co, Ni, Cu and Zn). The ligands were characterized by their physical (color, melting point, yield and solubility), spectral (UV-Vis, FT-IR, LC-MS, 1H NMR and 13C NMR) and elemental data. The structures of the metal complexes (1)-(12) were evaluated through their physical (magnetic and conductance), spectral (UV-Vis, FT-IR and LC-MS) and elemental data. The molecular geometries of ligands and their selected metal complexes were optimized at their ground state energies by B3LYP level of density functional theory (DFT) utilizing 6-311+G (d, p) and LanL2DZ basis set. The first principle study has been discussed for the electronic properties, the molecular electrostatic possibilities as well as the quantum chemical identifiers. An obvious transition of intramolecular charge had been ascertained from the occupied to the unoccupied molecular orbitals. The UV-Vis analysis was performed through time-dependent density functional theory (TD-DFT) by CAM-B3LYP/6-311+G (d, p) function. The in vitro antimicrobial activity was studied against two fungal (Aspergillus niger and Aspergillus flavus) and four bacterial (Staphylococcus aureus, Klebsiela pneumoniae, Escherichia coli and Bacillus subtilis) species. The antioxidant activity was executed as antiradical DPPH scavenging activity (%), total iron reducing power (%) and total phenolic contents (mg GAE g-1). Additionally, enzyme inhibition activity was done against four enzymes (Protease, α-Amylase, Acetylcholinesterase and Butyrylcholinesterase). All the synthetic products exhibited significant bioactivity which were found to enhance upon chelation due to phenomenon of charge transfer from metal to ligand.

Structure-based designing and synthesis of 2-phenylchromone derivatives as potent tyrosinase inhibitors: In vitro and in silico studies.

The present study describes the discovery of novel inhibitors of mushroom tyrosinase enzyme. For that purpose, a series of varyingly substituted 2-phenylchromone analogues 1-28 were synthesized and characterized in detail by various spectroscopic techniques (UV-Vis, FTIR, 1H NMR, 13C NMR) and mass spectrometry. All the derivatives (1-28) were screened in vitro for their inhibitory potential against mushroom tyrosinase enzyme. Interestingly, all the synthetic compounds displayed good to excellent inhibitory activity with IC50 values ranging from 0.093 ± 0.003 µg/ml to 23.58 ± 0.94 µg/ml for brominated 3-hydroxy-2-phenylchromones and 0.22 ± 0.017 µg/ml to 22.22 ± 1.1 µg/ml for brominated 2-phenylchromones against tyrosinase in comparison to the standard kojic acid (IC50 = 1.79 ± 0.64 µg/ml). Remarkably, the bromine atoms attached on ring A attribute to increases the inhibitory potential of 2-phenylchromone moiety and anti-tyrosinase assay demonstrated that compound 10 (IC50 = 0.093 ± 0.003 µg/ml) was found almost nineteenfold, 11 (IC50 = 0.126 ± 0.015 µg/ml) fourteenfold and 26 (IC50 = 0.22 ± 0.017 µg/ml) about eightfold more active than the positive control. Notably, among the already literature reported tyrosinase inhibitors, these analogues have been found the most active inhibitors of mushroom tyrosinase with the lowest possible IC50 values. To design and develop novel tyrosinase inhibitors using 2-phenylchromone as a structural motif in the future, a limited structure-activity relationship was established. Moreover, in silico studies were carried out to rationalize the binding mode of interactions of all the targeted compounds (1-28) with the active site of enzymes. The experimental and theoretical results are in parallel with one another. In addition, molecular description was performed with the drug-likeness and bioactivity scores. Computational analysis predicted that few compounds are in a linear correlation with Lipinski's RO5 indicating superb drug-likeness and bioactivity score for drug targets.

Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies.

To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1H-, 13C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes.

Synthesis, structure-activity relationship and molecular docking studies of 3-O-flavonol glycosides as cholinesterase inhibitors.

The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3-O-flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3-O-flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, 1H, 13C NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds (21-30) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another.

Antimicrobial metal-based thiophene derived compounds.

A novel series of thiophene derived Schiff bases and their transition metal- [Co(II), Cu(II), Zn(II), Ni(II)] based compounds are reported. The Schiff bases act as tridentate ligands toward metal ions via azomethine-N, deprotonated-N of ammine substituents and S-atom of thienyl moiety. The synthesized ligands along with their metal complexes were screened for their in vitro antibacterial activity against six bacterial pathogens (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and for antifungal activity against six fungal pathogens (Trichophytonlongifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata). The results of antimicrobial studies revealed the free ligands to possess potential activity which significantly increased upon chelation.

Synthesis, structure elucidation, SC-XRD/DFT, molecular modelling simulations and DNA binding studies of 3,5-diphenyl-4,5-dihydro-1H-pyrazole chalcones.

Deoxyribonucleic acid (DNA) acts as the most important intracellular target for various drugs. Exploring the DNA binding interactions of small bioactive molecules offers a structural guideline for designing new drugs with higher clinical efficacy and enhanced selectivity. This study presents the facile synthesis of pyrazoline-derived compounds (4a)-(4f) by reacting substituted chalcones with hydrazine hydrate using formic acid. The structure elucidation of substituted pyrazoline compounds was carried out using 1H-NMR, FT-IR and elemental analyses. While the crystal structures of two compounds (4a) and (4b) have been resolved by single-crystal X-ray diffraction (SC-XRD) analysis. Hirshfeld surface analysis also endorsed their greater molecular stability. Computational calculations at DFT/B3LYP/6-311++G(d,p) were executed to compare the structural properties (bond angle and bond length) and explore reactivity descriptors, frontier molecular orbitals (FMO), Mulliken atomic charges (MAC), molecular electrostatic potential (MEP) and electronic properties. All the compounds were evaluated for DNA binding interactions by UV-Vis spectrophotometric analysis. The results revealed that compounds (4a)-(4f) bind to DNA via non-covalent binding mode having binding constant values ranging from 1.22 × 103 to 6.81 × 104 M-1. The negative values of Gibbs free energy also proved the interaction of studied compounds with DNA as a spontaneous process. The findings of molecular docking simulations depicted that these studied compounds showed significant binding interactions with DNA and these results were consistent with experimental findings. Compound (4b) was concluded as the most potent compound of the series with the highest binding constant (4.95 × 104) and strongest binding affinity (-8.48 kcal/mol).Communicated by Ramaswamy H. Sarma.

Metal Based Bioactive Nitrogen and Oxygen Donor Mono and Bis Schiff Bases: Design, Synthesis, Spectral Characterization, Computational Analysis and Antibacterial Screening.

The scientific interest in developing the advanced metal based compounds to inhibit and control bacterial infections is continuously rising. Keeping in view their pharmacological significance, two new bioactive symmetrical phenylenediamine mono- and bis-Schiff bases, 2-{[(4-aminophenyl)imino]methyl}-6-methoxyphenol (L1) and 2,2'-{benzene-1,2-diylbis[nitrilomethylylidene]}bis(6-methoxyphenol) (L2) have been synthesized and characterized by using physical techniques, spectral methods, elemental and DFT based computational analysis with B3LYP/6-311++G(d, p) basis set. Furthermore, the synthesized ligands were complexed with VO, Mn, Co, Ni, Cu and Zn ions in ratio [M:L,1:2 and 1:1], respectively. All the complexes exhibited significant antibacterial action against all tested bacterial strains. But overall, the zinc complexes possessed higher antibacterial activity. These results concluded that metal complexes might be promising induction in the upcoming time for medical purposes.

Heating effect on quality characteristics of mixed canola cooking oils.

BACKGROUND: The subcontinent is famous for its variety of seasonal foods cooked in vegetable seed cooking oils at elevated heating. Oils are often of poor quality that effect to consumer health. The work, therefore, planned to examine the effects of heat on the quality of mixed canola cooking oils (MCCOs). MCCOs were analyzed by preparing volatile fatty acid methyl esters (FAMEs) and for physiochemical properties. RESULTS: A major change was observed in the FAs composition of various MCCOs as coded K-1 to K-5. MCCOs were found rich in unsaturated 9-octadecanoic acid (oleic acid C18:1) and 9, 12-octadecadienoic acid (linoleic acid C18:2) along saturated octadecanoic acid (stearic acid C18:0). Results reveals that canola oil samples are mixed in the range of 4-30% with other vegetable oils and animal fats. The quality of canola cooking oils further reduced after heating to 100 °C, 200 °C and 350 °C, respectively. Quality parameters of MCCOs were significantly altered after heating and found as color (510-520 nm to 570-600 nm), mass 220-237 g to 210-225 g, volume 250 mL to 239 mL, pH (6.76-6.89), specific gravity (0.87-0.92), refractive index (1.471-1.475), saponification value (SV) (0.7-2.5), un-saponifiable matter (2.4-9.8%) and acid value (AV) (1.20-5.0 mg KOH). CONCLUSION: Heating of oils at elevated temperature have shown a significant effect on pH, specific gravity and un-saponifiable matter (p-value < 0.05). Large changes in the physicochemical parameters and FAs composition help to develop a conclusion that cooking at high temperatures affects the quality of mixed canola cooking oils.

Quantum chemical designing of novel fullerene-free acceptor molecules for organic solar cell applications.

Organic solar cells (OSCs) with bulk heterojunction (BHJ) structures consisting of electron-donor and electron-acceptor materials have achieved impressive progress over the past decade, demonstrating their great potential in practical applications. In this study, we have designed five fullerene-free acceptor-based molecules containing indaceno-dithiophene as a central core moiety. We studied the optoelectronic features of these newly architecture molecules by using DFT and TD-DFT approaches. For the investigation of the optoelectronic characteristics of the reference and newly designed molecules, we performed different parameters including FMO's, absorption maxima, excitation energy, transition density matrix (TDM) along with binding energy, dipole moment, the partial density of states, charge mobility, and charge transfer analysis. Among all engineered molecules, SK1 has proven to be the most efficient solar cell due to its promising optoelectronic and photovoltaic properties. SK1 reveals smaller band-gap (Egap = 1.959 eV) and lesser λh (0.0070 eV) and λe (0.0051 eV). SK1 illustrated comparable binding energy value (0.33 eV) and lowest excitation energy (1.62 eV) which will lead to improved power conversion efficiency values. The SK1 molecule demonstrated the highest λmax value (764 nm) in the solvent phase which could lead to redshift absorption for achieving the high efficiency of OSCs. This molecular modeling approves that the best working efficiency of organic solar devices can be achieved by terminal group modifications due to their promising photovoltaic and optoelectronic properties. It is evident from the current analysis that all the theoretically fabricated molecules (SK1-SK5) are fabulous and highly suggested to experimental workers for their synthesis and advancement of these highly competent solar devices in the future.

Metal incorporated aminothiazole-derived compounds: synthesis, density function theory analysis, in vitro antibacterial and antioxidant evaluation.

The present study advocates the combined experimental and computational study of metal-based aminothiazole-derived Schiff base ligands. The structure and electronic properties of ligands have been experimentally studied by spectroscopic methods (UV-Vis, FT-IR, 1H-NMR and 13C-NMR), mass spectrometry, elemental analysis and theoretically by density function theory (DFT). Computational calculations employing the B3LYP/6-31 + G(d,p) functional of DFT were executed to explore the optimized geometrical structures of ligands along with geometric parameters, molecular electrostatic potential (MEP) surfaces and frontier molecular orbital (FMO) energies. Global reactivity parameters estimated from FMO energy gaps signified the bioactive nature of ligands. The synthesized ligands were used for chelation with 3d-transition metals [VO(IV), Cr(III), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)] in 1 : 2 (metal : ligand) molar ratio. The spectral and magnetic results confirmed the formation of octahedral geometry around all the divalent and trivalent metal centres, whereas the tetravalent vanadyl centres were confirmed to have square-pyramidal geometry. All the as-synthesized compounds were investigated for in vitro antibacterial potential against two Gram-negative (Salmonella typhimurium and Escherichia coli) and two Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacteria. Antibacterial assay results displayed pronounced activity, and their activity is comparable to that of a standard drug (streptomycin). The antioxidant potential of these compounds was assessed by employing diphenyl picryl hydrazide radical scavenging activity. The results displayed that all the metal chelates have exhibited more bioactivity in contrast with free ligands. The chelation was the main reason for their enhanced bioactivity. These results indicated that the thiazole metal-based compounds could be exploited as antioxidant and antimicrobial candidates.

Green photosensitisers for the degradation of selected pesticides of high risk in most susceptible food: A safer approach.

Pesticides are the leading defence against pests, but their unsafe use reciprocates the pesticide residues in highly susceptible food and is becoming a serious risk for human health. In this study, mint extract and riboflavin were tested as photosensitisers in combination with light irradiation of different frequencies, employed for various time intervals to improve the photo-degradation of deltamethrin (DM) and lambda cyhalothrin (λ-CHT) in cauliflower. Different source of light was studied, either in ultraviolet range (UV-C, 254 nm or UV-A, 320-380 nm) or sunlight simulator (> 380-800 nm). The degradation of the pesticides varied depending on the type of photosensitiser and light source. Photo-degradation of the DM and λ-CHT was enhanced by applying the mint extracts and riboflavin and a more significant degradation was achieved with UV-C than with either UV-A or sunlight, reaching a maximum decrement of the concentration by 67-76%. The light treatments did not significantly affect the in-vitro antioxidant activity of the natural antioxidants in cauliflower. A calculated dietary risk assessment revealed that obvious dietary health hazards of DM and λ-CHT pesticides when sprayed on cauliflower for pest control. The use of green chemical photosensitisers (mint extract and riboflavin) in combination with UV light irradiation represents a novel, sustainable, and safe approach to pesticide reduction in produce.

Exploring 3-Benzyloxyflavones as new lead cholinesterase inhibitors: synthesis, structure-activity relationship and molecular modelling simulations.

In this protocol, a series of 3-benzyloxyflavone derivatives have been designed, synthesized, characterized and investigated in vitro as cholinesterase inhibitors. The findings showed that all the synthesized target compounds (1-10) are potent dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with varying IC50 values. In comparison, they are more active against AChE than BChE. Remarkably, amongst the series, the compound 2 was identified as the most active inhibitor of both AChE (IC50 = 0.05 ± 0.01 µM) and BChE (IC50 = 0.09 ± 0.02 µM) relative to the standard Donepezil (IC50 = 0.09 ± 0.01 for AChE and 0.13 ± 0.04 µM for BChE). Moreover, the derivatives 5 (IC50 = 0.07 ± 0.02 µM) and 10 (0.08 ± 0.02 µM) exhibited the highest selective inhibition against AChE as compared to the standard. Preliminary structure-activity relationship was established and thus found that cholinesterase inhibitory activities of these compounds are highly dependent on the nature and position of various substituents on Ring-B of the 3-Benzyloxyflavone scaffolds. In order to find out the nature of binding interactions of the compounds and active sites of the enzymes, molecular docking studies were carried out.[Formula: see text]HIGHLIGHTS3-benzyloxyflavone analogues were designed, synthesized and characterized.The target molecules (1-10) were evaluated for their inhibitory potential against AChE and BChE inhibitory activities.Limited structure-activity relationship was developed based on the different substituent patterns on aryl part.Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interactions at the active pocket site of the enzyme.Communicated by Ramaswamy H. Sarma.

Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity.

The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H2LBn][Cl]2 (2), and [H2LMe][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2L, 1). The Pd(II) complexes, [Pd(LBn)2][Cl]2 (4), [Pd(LMe)2][Cl][TfO] (5), Pd(LBn)Cl2 (6) and Pd(LMe)Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGbo. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies.

Synthesis of new Pro-PYE ligands as co-catalysts toward Pd-catalyzed Heck-Mizoroki cross coupling reactions.

The present research work describes the synthesis of five new ligands containing pyridinium amine, [H2L1][OTf]2-[H2L5][I]2 from two new precursors, [P3 Et][I] and [P2 Me][CF3SO3]. The structure elucidations of the compounds were confirmed by multinuclear NMR (1H, 13C), FT-IR and by single crystal XRD techniques. Theoretical DFT studies were carried out to get better insight into the electronic levels and structural features of all the molecules. These synthesized new Pro-PYE ligands [H2L1][OTf]2-[H2L5][I]2 were found to be significantly active as co-catalysts for Pd(CH3CO2)2 toward Heck-Mizoroki coupling reactions with wide substrate scope in the order of [H2L1][OTf]2 ≫ [H2L2][OTf]2 > [H2L3][OTf]2 > [H2L4][OTf]2 > [H2L5][I]2.

Synthesis, spectral characterization, and biological evaluation of transition metal complexes of bidentate N, o donor schiff bases.

New series of three bidentate N, O donor type Schiff bases (L (1) )-(L (3) ) were prepared by using ethylene-1,2-diamine with 5-methyl furfural, 2-anisaldehyde, and 2-hydroxybenzaldehyde in an equimolar ratio. These ligands were further complexed with Co(II), Cu(II), Ni(II), and Zn(II) metals to produce their new metal complexes having an octahedral geometry. These compounds were characterized on the basis of their physical, spectral, and analytical data. Elemental analysis and spectral data of the uncomplexed ligands and their metal(II) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds. All ligands and their metal complexes were screened for antimicrobial activity. The results of antimicrobial activity indicated that metal complexes have significantly higher activity than corresponding ligands. This higher activity might be due to chelation process which reduces the polarity of metal ion by coordinating with ligands.