Occurrence of selected antibiotics in urban rivers in northwest Pakistan and assessment of ecotoxicological and antimicrobial resistance risks.

Antibiotics in aquatic systems of developing countries are a growing concern, particularly with the potential ecological risks and emergence of antimicrobial resistance. In Pakistan, antibiotics are widely consumed and released untreated into rivers, however, there is little information on their occurrence and potential risks. In this study, the concentrations and risk assessment of three commonly consumed antibiotics, ciprofloxacin (CIP), amoxicillin (AMX), and cefixime (CFM) belonging to different classes of fluoroquinolone, penicillin, and cephalosporin respectively were investigated in the Kabul River and its two tributaries, Bara River and Shah Alam River in the northwest region of the country. Composite samples were collected in different sampling campaigns and analyzed using the LC-ESI-MS/MS technique. All three antibiotics were found in higher concentrations ranging from 410 to 1810 ng/L, 180-850 ng/L, and 120-600 ng/L for CIP, AMX, and CFM respectively. The Friedman and Wilcoxon signed-ranked tests revealed insignificant differences in average concentrations of each antibiotic in the three rivers and the Pearson Correlation showed a significant positive correlation of CIP with both AMX and CFM indicating their similar pollution sources. Ecotoxicological risk assessment showed a higher risk to algae and bacteria (P. putida) in the rivers with CIP posing a greater risk. The potential risk of antimicrobial resistance development (ARD) was higher in all the three rivers, particularly in Kabul River where maximum risk quotients (RQARD) of 28.3, 9.4 and 3.4 were noted for CIP, CFM and AMX respectively. The human health (HH) risk was insignificant, though the RQHH was higher for the lower age groups (0-3 months). In addition, the combined flux of the antibiotics in the Kabul River was estimated as 59 tons/year with CIP having a significant flux relative to the other antibiotics.

Novel Cu(II) complexes as DNA-destabilizing agents and their DNA nuclease activity.

Here, we report a series of four novel Cu complexes, namely 2-(piperidin-1-ylmethyl)quinoline copper(II) nitrate, [LACu(NO3)2] (Cu1), 4-(quinolin-2-ylmethyl)morpholine copper(II) nitrate, [LBCu(NO3)2] (Cu2), 4-(quinolin-2-ylmethyl)morpholine copper(II) chloride, [LBCuCl2] (Cu3), and 2-(piperidin-1-ylmethyl)pyridine copper(II) chloride, [LCCu(µ-Cl)Cl]2 (Cu4). X-ray diffraction studies revealed that the geometry around the Cu(II) center could be best described as distorted octahedral in Cu1 and Cu2, whereas Cu3 and Cu4 showed distorted tetrahedral and square pyramidal geometries, respectively. DNA binding studies showed that Cu complexes Cu1-3 containing quinoline interacted via minor groove binding, whereas the Cu4 complex containing pyridine interacted via intercalation. All Cu complexes containing quinoline and pyridine caused destabilization of DNA at specific homogeneous G-C regions. The Cu1-3 complexes as groove binders destabilized the DNA structure much more than the Cu4 complex as an intercalator. Regarding groove binders, the Cu2 complex containing quinoline and morpholine caused the highest distortion and destabilization of the DNA structure, leading to high DNA cleavage efficiency.

Dihydropyrazole Derivatives Act as Potent α-Amylase Inhibitors and Free Radical Scavengers: Synthesis, Bioactivity Evaluation, Structure-Activity Relationship, ADMET, and Molecular Docking Studies.

Dihydropyrazole (1-22) derivatives were synthesized from already synthesized chalcones. The structures of all of the synthesized compounds were confirmed by elemental analysis and various spectroscopic techniques. Furthermore, the synthesized compounds were screened against α amylase as well as investigated for antioxidant activities. The synthesized compounds demonstrate good to excellent antioxidant activities with IC50 values ranging between 30.03 and 913.58 µM. Among the 22 evaluated compounds, 11 compounds exhibit excellent activity relative to the standard ascorbic acid IC50 = 287.30 µM. Interestingly, all of the evaluated compounds show good to excellent α amylase activity with IC50 values lying in the range between 0.5509 and 810.73 µM as compared to the standard acarbose IC50 = 73.12 µM. Among the investigated compounds, five compounds demonstrate better activity compared to the standard. In order to investigate the binding interactions of the evaluated compounds with amylase protein, molecular docking studies were conducted, which show an excellent docking score as compared to the standard. Furthermore, the physiochemical properties, drug likeness, and ADMET were investigated, and it was found that none of the compounds violate Lipiniski's rule of five, which shows that this class of compounds has enough potential to be used as a drug candidate in the near future.

Thiophene-Derived Schiff Base Complexes: Synthesis, Characterization, Antimicrobial Properties, and Molecular Docking.

Novel thiophene-derived Schiff base ligand DE, where DE is (E)-N1,N1-diethyl-N2-(thiophen-2-ylmethylene)ethane-1,2-diamine, and the corresponding M(II) complexes, [M(DE)X2] (M = Cu or Zn, X = Cl; M = Cd, X = Br), were prepared and structurally characterized. X-ray diffraction studies revealed that the geometry around the center of the M(II) complexes, [Zn(DE)Cl2] and [Cd(DE)Br2], could be best described as a distorted tetrahedral. In vitro antimicrobial screening of DE and its corresponding M(II) complexes, [M(DE)X2], was performed. The complexes were more potent and showed higher activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, fungi Candida albicans, and protozoa Leishmania major compared to the ligand. Among the studied complexes, [Cd(DE)Br2] exhibited the most promising antimicrobial activity against all the tested microbes compared to its analogs. These results were further supported by molecular docking studies. We believe that these complexes may significantly contribute to the efficient designing of metal-derived agents to treat microbial infections.

Biosynthesis and Anti-inflammatory Activity of Zinc Oxide Nanoparticles Using Leaf Extract of Senecio chrysanthemoides.

Nanotechnology has recently appeared as an important study subject in modern material sciences. Greener synthesis of nanoparticles has gained the attention of many scientists because of its integral characteristics such as effectiveness, eco-friendly, and low cost. In the present study by following the green synthesis approach, zinc oxide nanoparticles (ZnO NPs) were formed for the very first time by using Senecio chrysanthemoides leaf extract as a reducing agent. The UV-Vis spectrophotometer was used to study the synthesized ZnO NPs, and the specific peak was found to be at 349 nm. The characteristic Fourier transform infrared (FTIR) peak was found to be at 449 cm-1 which displays the peak of ZnO molecules. The surface morphology of the ZnO NPs was determined via scanning electron microscopy (SEM). The energy-dispersive X-ray spectroscopy (EDX) study showed that the synthesized ZnO NPs are present at the weight percentage of 66.38%. The X-ray diffraction (XRD) spectrum confirmed the hexagonal phase wurtzite structure, with the average particle size of 31 nm, and demonstrated the crystalline structure of ZnO NPs. Additionally, to all these experiments, we compared the anti-inflammatory properties of biogenic ZnO NPs to a standard drug. Biosynthesized ZnO NPs have revealed an effective anti-inflammatory activity at a higher concentration (100 mL-1) and showed 73% inhibition in comparison with diclofenac sodium drug. Zinc oxide was shown to be compatible with diclofenac sodium, according to the results. The ZnO NPs produced using the greener synthesis process have the potential to be used in a broad range of fields and also used as a good anti-inflammatory agent.

Synthesis and Characterization of Zinc(II), Cadmium(II), and Palladium(II) Complexes with the Thiophene-Derived Schiff Base Ligand.

Zn(II), Pd(II), and Cd(II) complexes, [L TH MCl 2 ] (M = Zn, Pd; X = Br, Cl) and [L TH Cd(µ-X)X] n (X = Cl, Br; n = n, 2), supported by the (E)-N 1,N 1-dimethyl-N 2-(thiophen-2-ylmethylene)ethane-1,2-diamine (L TH ) ligand are synthesized and structurally characterized. Density functional theory (DFT) electronic structure calculations and variable-temperature NMR support the presence of two conformers and a dynamic interconversion process of the minor conformer to the major one in solution. It is found that the existence of two relevant complex conformers and their respective ratios in solution depend on the central metal ions and counter ions, either Cl- or Br-. Among the two relevant conformers, a single conformer is crystallized and X-ray diffraction analysis revealed a distorted tetrahedral geometry for Zn(II) complexes, and a distorted square planar and square pyramidal geometry for Pd(II) and Cd(II) complexes, respectively. It is shown that [L TH MCl 2 ]/LiO i Pr (M = Zn, Pd) and [L TH Cd(µ-Cl)Cl] n /LiO i Pr can effectively catalyze the ring-opening polymerization (ROP) reaction of rac-lactide (rac-LA) with 94% conversion within 30 s with [L TH ZnCl 2 ]/LiO i Pr at 0 °C. Overall, hetero-enriched poly(lactic acid)s (PLAs) were provided by these catalytic systems with [L TH ZnCl 2 ]/LiO i Pr producing PLA with higher heterotactic bias (P r up to 0.74 at 0 °C).

Catalytic performance of tridentate versus bidentate Co(ii) complexes supported by Schiff base ligands in vinyl addition polymerization of norbornene.

A series of Co(ii) complexes supported by Schiff base ligands, LA-LC, where LA, LB, and LC are (E)-3-methoxy-N-(quinolin-2-ylmethylene)propan-1-amine, (E)-N 1,N 1-dimethyl-N 2-(pyridin-2-ylmethylene)ethane-1,2-diamine, and (E)-N 1,N 1-dimethyl-N 2-(thiophen-2-ylmethylene)ethane-1,2-diamine, respectively, were designed and synthesized. Structural studies revealed a distorted trigonal bipyramidal geometry for [LBCoCl2] and a distorted tetrahedral geometry for [LCCoCl2]. After activation with modified methyl aluminoxane (MMAO), all the Co(ii) complexes catalyzed the polymerization of norbornene (NB) to yield vinyl-type polynorbornenes (PNBs) with activities of up to 4.69 × 104 gPNB mol Co-1 h-1 at 25 °C. High-molecular-weight (M n of up to 1.71 × 105 g mol-1) soluble PNBs with moderate molecular-weight distributions (MWD) were obtained. The activity of the Co(ii)/MMAO catalytic system is influenced by the steric hindrance and electronic properties of the ligands.

Synthesis, structures, and catalytic efficiency in ring opening polymerization of rac-lactide with tridentate vs. bidentate cobalt(ii), zinc(ii), and cadmium(ii) complexes containing N-substituted N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)amine ligands.

A series of Co(ii), Zn(ii), and Cd(ii) complexes supported by 1-(3,5-dimethyl-1H-pyrazol-1-yl)-N-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-N-(furan-2-ylmethyl)methanamine (LA) and N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)-4-isopropylaniline (LB) were synthesized. The direct chelation of CoCl2·6H2O, ZnCl2, and CdBr2·4H2O by the ligands produced [LnMX2] (Ln = LA or LB; M = Zn or Co, with X = Cl; M = Cd, with X = Br) complexes in high yields. Structural studies revealed that [LBCoCl2] and [LBZnCl2] adopted distorted tetrahedral geometries, as LB coordinated the metal centers in a bidentate fashion, while LA coordinated the metal centers in a tridentate fashion through the nitrogen atoms of the pyrazole and amine moieties, so that [LACoCl2] and [LAZnCl2] exhibited trigonal bipyramidal geometries and [LACdBr2] a square pyramidal geometry. [LBCdBr2] has two Cd-containing structures per unit cell, whereby one Cd center adopted a distorted tetrahedral geometry and the other exhibited square bipyramidal geometry. The in situ-generated alkyl derivatives of the synthesized complexes were assessed in the ring-opening polymerization of rac-lactide. Heterotactic polylactides (PLAs) were furnished with all complexes. The [LBZnCl2]/MeLi system produced PLA with a superior heterotactic bias (P r up to 0.94) at -25 °C. PLAs with wide-ranging polydispersity indices (1.16-2.23) and low molecular weights were produced in all cases, irrespective of the specific M(II) center and ancillary ligand utilized.

Stereoselective polymerization of methyl methacrylate and rac-lactide mediated by iminomethylpyridine based Cu(ii) complexes.

Iminomethylpyridine based copper(ii) complexes [LnCuCl2] (Ln = LA, LC-LF) and [LBCu(µ-Cl)Cl]2 have been synthesized and characterized. [LCCuCl2] and [LECuCl2] were identified to possess distorted square pyramidal geometries obtained via N,N'-bidentate coordination, whereas [LFCuCl2] showed N,N',N''-coordination of the corresponding ligand (LF). [LBCu(µ-Cl)Cl]2 was found to be dimeric with a distorted square pyramidal geometry around the Cu(ii) center. The catalytic properties of dimethyl derivatives, generated in situ, towards the ring opening polymerization (ROP) of rac-LA were investigated. All the complexes efficiently polymerized rac-LA and yielded heterotactic poly(lactide) (PLA) (P r up to 0.88 at -25 °C). Further, these complexes could effectively polymerize methyl methacrylate (MMA) at 60 °C in the presence of modified methylaluminoxane (MMAO), to furnish syndio-enriched PMMA. The catalytic efficacies of synthesized complexes can be correlated to the suitable complexity of the substituents attached to the ligand architecture. Thus, both the steric and electronic properties as well as the orientation of the various substituents relative to the xy plane of the pyridyl moiety and metal center play an influential role in steering catalytic activities, whereas the selectivities remain unaffected.

Dichlorido{2,6-diisopropyl-N-[(S)-pyrrolidin-2-ylmeth-yl]aniline-κ(2) N,N'}palladium(II).

In the title compound, [PdCl2(C17H28N2)], the Pd(II) atom displays a square-planar coordination involving two N atoms of a 2,6-diisopropyl-N-[(S)-pyrrolidin-2-ylmeth-yl]aniline ligand and two chloride ligands, with a deviation of 0.090 (1) Šfor the Pd(II) atom from the best plane. The absolute configuration of the chiral C atom of the pyrrolidine ring is S, which induces R configurations at the two N atoms of the aniline ligand. Optical isomerism arising from the chelate five-membered ring is configured as δ. The Pd-N bond lengths are 2.040 (3) and 2.072 (2) Å, and the Pd-Cl bond lengths are 2.3055 (8) and 2.3160 (8) Å. In the crystal, pairs of N-H⋯Cl hydrogen bonds link mol-ecules into discrete dimers.

(2R)-N-(2-Benzoyl-phen-yl)-1-benzyl-pyrrolidine-2-carboxamide.

In the title compound, C(25)H(24)N(2)O(2), the dihedral angle between the two benzene rings of the benzophenone moiety is 59.10 (6)°. An intra-molecular, bifurcated N-H⋯(O,N) hydrogen bond, which generates S(6) and S(5) rings, respectively, helps to establish the overall conformation of the mol-ecule.

Dichlorido[(S)-N-(1-phenyl-ethyl-idene)-1-(pyridin-2-yl)ethanamine-κN,N']zinc(II) dichloro-methane solvate.

In the title compound, [ZnCl(2)(C(15)H(16)N(2))]·CH(2)Cl(2), the Zn(II) atom has a distorted tetra-hedral coordination by two Cl atoms and two N atoms from the organic ligand [the average Zn-N and Zn-Cl bond lengths are 2.060 (4) Šand Zn-Cl = 2.179 (16) Å, respectively]. The dihedral angle between the N-Zn-N and Cl-Zn-Cl planes is 89.9 (1)°. The phenyl ring forms a dihedral angle of 40.6 (5)° with the imine plane.