Essential Oil from Tagetes minuta Has Antiquorum Sensing and Antibiofilm Potential against Pseudomonas aeruginosa Strain PAO1.

Biofilms are complex communities of microorganisms that are enclosed in a matrix that shows increased resistance to antimicrobial and immunological encounters. Mostly, the traditional methods to control biofilm are exhausted; therefore, the aim is to evaluate the potential of essential oil (EO) from Tagetes minuta to encounter biofilm and other related virulence factors. The EO of T. minuta was extracted through steam-distillation, analyzed on gas chromatography-mass spectrometry, and the biofilm inhibition assays were performed with various concentrations of EO. Mainly the EO from T. minuta contains cis-ß-ocimene (29.1%), trans-tagetenone (23.1%), and cis-tagetenone (17.7%). The virulence factors were monitored while applying different concentrations of EO and it was recorded that the EO from T. minuta significantly inhibited the virulence factors linked with quorum sensing (QS), such as pyocyanin production, protease production, and swarming motility. Biofilm formation is one of the most important virulence factors associated with the QS pathway and was inhibited up to 79% in the presence of EO. Antibacterial activity against the PAO1 of EO was not so promising particularly and it has high MIC (325 µg/mL) and MBC (5000 µg/mL). EO is quite efficient to inhibit biofilm in a very small concentration of 20 µg/mL, which confirms that the biofilm inhibition by EO is not by killing bacterial cells but by inhibiting the QS pathway. The study on PAO1 constructs carrying various QS reported genes confirmed that the EO interferes with the QS pathway that ultimately controls various virulence factors caused by PAO1.

Designing and Exploration of the Biological Potentials of Novel Centrosymmetric Heteroleptic Copper(II) Carboxylates.

Copper(II) complexes with a general formula [Cu2(3,4-F2C6H3CH2COO)4(L)2], where L = 2-methylpyridine (1) and 3-methylpyridine (2), are reported here. The FTIR spectra of the complexes confirmed the bridging bidentate coordination mode of the carboxylate ligand. The low (475 and 449 cm-1) and strong (727 & 725 cm-1) intensity bands in the FTIR spectra, due to Cu-N stretches and pyridyl ring vibrations, confirmed coordination of the 2-/3-methyl pyridine co-ligands in complexes 1 and 2, respectively. A binuclear paddlewheel structural arrangement with a square pyramidal geometry was confirmed for copper atoms in the complexes via single-crystal X-ray analysis. The DPPH, •OH radical, and α-amylase enzyme inhibition assays showed higher activities for the complexes than for the free ligand acid. The binding constant (Kb = 1.32 × 105 for 1 and 5.33 × 105 for 2) calculated via UV-VIS absorption measurements and docking scores (-6.59 for 1 and -7.43 for 2) calculated via molecular docking showed higher SS-DNA binding potential for 2 compared to 1. Viscosity measurement also reflected higher DNA binding ability for 2 than 1. Both complexes 1 and 2 (docking scores of -7.43 and -6.95, respectively) were found to be more active inhibitors than the free ligand acid (docking score of -5.5159) against the target α-amylase protein. This in silico study has shown that the herein reported compounds follow the rules of drug-likeness and exhibit good potential for bioavailability.

Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights.

The present study was designed to evaluate the in vitro and in silico potential of the Schiff bases (Z)-4-ethoxy-N-((5-nitrothiophen-2-yl)methylene)benzenamine (1) and (Z)-2,4-diiodo-6-((2-methyl-3-nitrophenylimino)methyl)phenol (2). These Schiff bases were synthesized according to a reported method using ethanol as a solvent, and each reaction was monitored on a TLC until completion of the reaction. The structures of both compounds were elucidated using spectroscopic techniques such as UV-Vis, FTIR, 1H NMR and 13C NMR. Molecular structure was determined using single-crystal XRD, which revealed that compounds 1 and 2 were monoclinic and triclinic, respectively. Hirshfeld surface analysis (HS) and 2D fingerprint plots were used to determine the intermolecular interactions along the contact contribution in the crystalline molecules. The structures of both compounds were optimized through a hybrid functional method B3LYP using the 6-31G(d,p) basis set, and various structural parameters were studied. The experimental and theoretical parameters (bond angle and bond length) of the compounds were compared with each other and are in close agreement. The in vitro esterase potential of the synthesized compounds was checked using a spectrophotometric model, while in silico molecular docking studies were performed with AutoDock against two enzymes of the esterase family. The docking studies and the in vitro assessment predicted that such molecules could be used as enzyme inhibitors against the tested enzymes: acetylcholine esterase (AChE) and butyrylcholine esterase (BChE).

Syntheses and structural characterization of divalent metal complexes (Co, Ni, Pd and Zn) of sterically hindered thiourea ligand and a theoretical insight of their interaction with SARS-CoV-2 enzyme.

Reacting two equivalents of sterically hindered 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with CoCl2, NiBr2, PdX2 (X = Cl; Br) and ZnI2 in acetonitrile afforded the corresponding bulky thiourea ligand stabilized four coordinated monomeric [L2CoCl2] (1), [L2NiBr2] (2), [L2PdX2] (3a: X = Cl; 3b: X = Br) and [L2ZnI2] (4.2CH3CN) complexes. Compound 1, 2 and 4.2CH3CN are tetrahedral whereas Pd complexes (3a and 3b) are square planar. In solution, palladium complexes are dominated by cis-isomers. Structural characterization shows inter- and intramolecular hydrogen bonding. Hirshfeld surface and fingerprint plots indicated significant intermolecular interactions in the crystal network. Molecular docking analysis revealed relatively higher SARS-CoV-2 enzyme interacting abilities of the synthesized complexes compared to the free ligand. All compounds have been characterized by elemental analyses, NMR spectroscopy and single-crystal X-ray diffraction.

Carboxymethyl Cellulose/Gelatin Hydrogel Films Loaded with Zinc Oxide Nanoparticles for Sustainable Food Packaging Applications.

The current research work presented the synthesis of carboxymethyl cellulose-gelatin (CMC/GEL) blend and CMC/GEL/ZnO-Nps hydrogel films which were characterized by FT-IR and XRD, and applied to antibacterial and antioxidant activities for food preservation as well as for biomedical applications. ZnO-Nps were incorporated into the carboxymethyl cellulose (CMC) and gelatin (GEL) film-forming solution by solution casting followed by sonication. Homogenous mixing of ZnO-Nps with CMC/GEL blend improved thermal stability, mechanical properties, and moisture content of the neat CMC/GEL films. Further, a significant improvement was observed in the antibacterial activity and antioxidant properties of CMC/GEL/ZnO films against two food pathogens, Staphylococcus aureus and Escherichia coli. Overall, CMC/GEL/ZnO films are eco-friendly and can be applied in sustainable food packaging materials.

PMMA/ABS/CoCl2 Composites for Pharmaceutical Applications: Thermal, Antimicrobial, Antibiofilm, and Antioxidant Studies.

In this study, PMMA/ABS/CoCl2 ternary composite films were fabricated by the solution casting technique. The different weight ratios of cobalt chloride (≤10 wt) were incorporated into the PMMA/ABS blend (80:20). The chemical structure and thermal properties of the synthesized composites were assessed by FT-IR, TGA, and XRD. The biological properties of ternary composites, such as in vitro antibacterial activity and antioxidant capacity, were investigated. The enhanced thermal stability and promising antibacterial, selective antibiofilm, and potential antioxidant properties of PMMA/ABS/cobalt chloride composites demonstrated that they can be used for high-quality plastics and in many pharmaceutical applications.

Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species.

Anthocyanidins are the most abundant polyphenols in pomegranate juice. This class of molecules includes Delphinidin (Del), Cyanidin (Cya), and Pelargonidin (Pel). Using prostate, breast and pancreatic cancer cell lines PC3, MDA-MB-231, BxPC-3 and MiaPaCa-2, we show that anthocyanidins inhibit cell proliferation (measured by MTT assay) and induce apoptosis like cell death (measured by DNA/Histone ELISA). Copper chelator neocuproine and reactive oxygen species scavengers (thiourea for hydroxyl radical and superoxide dismutase for superoxide anion) significantly inhibit this reaction thus demonstrating that intracellular copper reacts with anthocyanidins in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitizes normal breast epithelial cells (MCF-10A) to Del-mediated growth inhibition as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters Ctr1 and ATP7A in MCF-10A cells, which is attenuated by the addition of Del in the medium. We propose that the copper mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of anthocyanidins.

Mononuclear Tricoordinate Copper(I) and Silver(I) Halide Complexes of a Sterically Bulky Thiourea Ligand and a Computational Insight of Their Interaction with Human Insulin.

Reaction of two equivalents of the bulky 1,3-bis(2,6-diethylphenyl)thiourea ligand (L) with MX (being M = Cu+, Ag+; and X = Cl-, Br-, I-) in acetonitrile afforded neutral complexes of the type [MXL2] [CuClL2].2CH3CN (1a); [CuBrL2].2CH3CN (1b); [CuIL2] (1c): [AgClL2] (2a); [AgBrL2] (2b) and [AgIL2] (2c). The two aromatic groups in free ligand were found to be trans with respect to the thiourea unit, which was a reason to link the ligand molecules via intermolecular hydrogen bonding. Intramolecular hydrogen bonding was observed in all metal complexes. The copper complexes 1a and 1b are acetonitrile solvated and show not only intra- but also intermolecular hydrogen bonding between the coordinated thiourea and the solvated acetonitrile molecules. Silver complexes reported here are the first examples of structurally characterized tricoordinated thiourea-stabilized monomeric silver(I) halides. Molecular docking studies were carried out to analyze the binding modes of the metal complexes inside the active site of the human insulin (HI) protein. Analysis of the docked conformations revealed that the electrostatic and aromatic interactions of the protein N-terminal residues (i.e., Phe and His) may assist in anchoring and stabilizing the metal complexes inside the active site. According to the results of docking studies, the silver complexes exhibited the strongest inhibitory capability against the HI protein, which possesses a deactivating group, directly bonded to silver. All compounds were fully characterized by elemental analysis, NMR spectroscopy, and molecular structures of the ligand, and five out of six metal complexes were also confirmed by single-crystal X-ray diffraction.

Synthesis, characterization, antioxidant, antileishmanial, anticancer, DNA and theoretical SARS-CoV-2 interaction studies of copper(II) carboxylate complexes.

Copper(II) carboxylate complexes [Cu2(OOCR)4L2] (1) and [Cu2(OOCR`)4OCO(R`)CuL2]n (2), where L = 2-methyl pyridine, R = 2-chlorophenyl acetate and R` = 2-fluorophenyl acetate were synthesized and characterized by FT-IR spectroscopy and single crystal X-ray analysis. Complex 1 exhibits the typical paddlewheel array of a dinuclear copper(II) complex with carboxylate ligands. In complex 2, this scaffold is further extended into a polymeric arrangement based on alternate paddlewheel and square planar moieties with distinct coordination spheres. The complexes showed better 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical scavenging activities and have been found to be more potent antileishmanial agents than their corresponding free ligand acid species. UV-Vis absorption titrations revealed good DNA binding abilities {Kb = 9.8 × 104 M-1 (1) and 9.9 × 104 M-1 (2)} implying partial intercalation of the complexes into DNA base pairs along with groove binding. The complexes displayed in vitro cytotoxic activity against malignant glioma U-87 (MG U87) cell lines. Computational docking studies further support complex-DNA binding by intercalation. Molecular docking investigations revealed probable interactions of the complexes with spike protein, the nucleocapsid protein of SARS-CoV-2 and with the angiotensin converting enzyme of human cells.

Coordination Chemistry of Bulky Aminopryridinates with Main Group and Transition Metals.

The coordination chemistry of bidentate aminopyridinato ligands (ApH), in particular 2-aminopyridines, is a highly popular area of research. Due to easy accessibility and versatility, 2-aminopyridines have played a prominent role as alternatives to cyclopentadienyl ligands in coordination chemistry. Easily modifiable steric bulks and the ability for fine-tuning of electronic effects have allowed researchers to control not only the metal-to-ligand stoichiometry but also the properties of their metal complexes. Previously, ligand redistribution was frequently observed for ligands of small steric demands. Bulky aminopyridinato ligands refer to ligands that incorporate alkyl-substituted phenyl groups at the amine/amido nitrogen and at the sixth position of the pyridine ring. The steric crowding allowed the stabilization of transition metals in unusually low oxidation conditions. One of the remarkable developments, for example, is the stabilization of metal-metal quintuple bonds by these ligands, thus providing a diamagnetic platform to study such systems chemically. Application of metal aminopyridinates in homogeneous catalysis has also broadened considerably in recent years. This review provides a comprehensive account of advances made with such ligands since their development for main group and transition elements.

Formation of a dimeric tungsten(i) complex via C-H activation.

An aminopyridinato ligand stabilized and coordinatively unsaturated dimeric tungsten(0) complex having an electronic structure with six metal centred HOMOs (σ2,π2,π2,δ2,δ2, and δ*2) has been isolated and structurally characterized. Its reaction with a cryptand leads to a C-H bond activation of one of the isopropyl groups of the N-ligand to form a dimeric tungsten(i) complex.

Novel cis-[(NHC)1(NHC)2(L)Cl]platinum(ii) complexes - synthesis, structures, and anticancer activities.

A general synthesis of novel platinum(ii) complexes bearing two different, cis-oriented, N-heterocyclic carbene (NHC) ligands is presented. Easily accessible cis-[PtII(NHC)(DMSO)] precursor complexes were converted to either cis-[PtII(NHC)2Cl2] complexes such as 5a and 5b, or to novel mixed cis-[PtII(NHC)1(NHC)2Cl2] complexes such as 5c-h by successive introduction of the individual carbene ligands. The 'symmetric' complexes 5a and 5b were also converted to cationic cis-[PtII(NHC)2(PPh3)Cl]+Cl- complexes 8a and 8b. The structures of the ten new complexes, comprising benzylated and alkylated imidazol-2-ylidene ligands, were analysed by 1H, 13C and 195Pt NMR spectroscopy and also by X-ray diffraction for 5a, 5d, 5h, and 8a. The neutral complexes 5 were cytotoxic against a panel of seven human cancer cell lines with IC50 values in the low micromolar range, while the cationic complexes 8 reached even nanomolar IC50 values. Complex 5h carrying the substitution pattern of the natural antitumoral agent Combretastatin A-4 showed a conspicuous specificity for cancer cell lines sensitive to this drug. In electrophoretic mobility shift assays, the cis-biscarbene complexes 5b and 8b led to an unwinding or aggregation of plasmid DNA, while the trans-biscarbene complex 1b showed no such effect.

Adjusting the DNA Interaction and Anticancer Activity of Pt(II) N-Heterocyclic Carbene Complexes by Steric Shielding of the Trans Leaving Group.

Five platinum(II) complexes bearing a (1,3-dibenzyl)imidazol-2-ylidene ligand but different leaving groups trans to it were examined for cytotoxicity, DNA and cell cycle interference, vascular disrupting properties, and nephrotoxicity. The cytotoxicity of complexes 3a-c increased with the steric shielding of their leaving chloride ligand, and complex 3c, featuring two triphenylphosphanes, was the most efficacious, with submicromolar IC50 concentrations. Complexes 3a-c interacted with DNA in electrophoretic mobility shift and ethidium bromide binding assays. The cationic complex 3c did not bind coordinatively to DNA but led to its aggregation, damage that is not amenable to the usual repair mechanisms. Accordingly, it arrested the cell cycle of melanoma cells in G1 phase, whereas cis-dichlorido[(1,3-dibenzyl)imidazol-2-ylidene](dimethyl sulfoxide) platinum(II) 3a induced G2/M phase arrest. Complex 3c also disrupted the blood vessels in the chorioallantoic membrane of fertilized chicken eggs. Ex vivo studies using precision-cut tissue slices suggested the nephrotoxicities of 3a-c to be clinically manageable.

From chromium-chromium quintuple bonds to molecular squares and porous coordination polymers.

Reaction of the quintuply bonded chromium(I) dimer [ApCrCrAp] (Ap = sterically demanding 2-aminopyridinate) with pyrazine yields a chromium(II) complex with a η(4):η(4) face-on coordinated pyrazine dianion. Reaction with 4,4'-bipyridine, on the other hand, completely cleaves the metal-metal bond, leading to a chromium(II)-based molecular square. XRD and magnetic measurements show ligand radical anions and a ferrimagnetic alignment of alternating metal and ligand magnetic moments. Controlled polymerization of the molecular square with pyrazine yields a porous coordination polymer featuring both reduced and nonreduced linkers.

CO2 and SO2 activation by a Cr-Cr quintuple bond.

A quintuply bonded dichromium complex stabilized by aminopyridinato ligands activates CO2 and SO2 by reducing the (formal) bond order of the metal-metal bonds. Oxygen abstraction is observed during CO2 activation. SO2 activation proceeds via formation of a unique dithionite complex/coordination. Furthermore, N2O activation was investigated and the formation of a tetrameric Cr-oxo complex was observed.

The ligand-based quintuple bond-shortening concept and some of its limitations.

Herein, the ligand-based concept of shortening quintuple bonds and some of its limitations are reported. In dichromium-diguanidinato complexes, the length of the quintuple bond can be influenced by the substituent at the central carbon atom of the used ligand. The guanidinato ligand with a 2,6-dimethylpiperidine backbone was found to be the optimal ligand. The reduction of its chromium(II) chloride-ate complex gave a quintuply bonded bimetallic complex with a Cr-Cr distance of 1.7056 (12) Å. Its metal-metal distance, the shortest observed in any stable compound yet, is of essentially the same length as that of the longest alkane C-C bond (1.704 (4) Å). Both molecules, the alkane and the Cr complex, are of remarkable stability. Furthermore, an unsupported Cr(I) dimer with an effective bond order (EBO) of 1.25 between the two metal atoms, indicated by CASSCF/CASPT2 calculations, was isolated as a by-product. The formation of this by-product indicates that with a certain bulk of the guanidinato ligand, other coordination isomers become relevant. Over-reduction takes place, and a chromium-arene sandwich complex structurally related to the classic dibenzene chromium complex was observed, even when bulkier substituents are introduced at the central carbon atom of the used guanidinato ligand.

Quintuple bond reactivity toward group 16 and 17 elements: addition vs insertion.

The low valent, coordinatively unsaturated, and formally quintuply bonded bimetallic aminopyridinato chromium complex 1 was investigated regarding its reactivity toward group 16 and 17 elements. Reaction of 1 with O(2) yielded a dimeric Cr oxo complex 2, a compound with a high formal oxidation state carrying both bridging and terminal oxo ligands. Reactions with the higher homologues of the group lead to the formation of dimeric Cr(II) complexes in which E(2)(2-) ligands were formed [E = S (3), Se (4), and Te (5)]. Here the quintuply bonded dichromium unit formally undergoes an addition reaction. Reaction of 1 with the homo diatomic molecules of the group 17 elements leads to products in which the Cr-Cr quintuple bond is inserted into the corresponding X(2) molecule [X = Cl (6), Br (7), and I (8)]. Complex 1 was also found to insert into the S-S and Se-Se bonds of 1,2-diphenyldisulfane or the corresponding selenium compound (complexes 9 and 10, respectively). All the compounds have been characterized by NMR and elemental analysis. Additionally, eight of the complexes have been characterized by X-ray analysis. The bimetallic Cr(II) complexes feature metal-metal distances between 1.8369(18) and 1.918(12) Å.

Highly active titanium-based olefin polymerization catalysts bearing bulky aminopyridinato ligands.

A series of titanium complexes have been prepared using either salt metathesis or amine elimination reactions. Reacting the potassium salt of Ap*H {Ap*H = N-(2,6-diisopropylphenyl)-[6-(2,4,6-triisopropylphenyl)pyridin-2-yl]amine} (1) with [TiCl(4)(THF)(2)] results in the formation of a nucleophilic ring-opening product of the coordinated tetrahydrofuran (THF) ligand [Ap*TiCl(2)(OC(4)H(8)Cl)] (7). Alkylation with benzylmagnesium chloride gave rise to the corresponding benzyl complex [Ap*TiBn(2)(OC(4)H(8)Cl)] (8). However, THF ring opening was overcome by adopting an amine elimination route instead of salt metathesis. Mono(aminopyridinato)titanium trichloro complexes were prepared in high yields using [(CH(3))(2)NTiCl(3)], together with the corresponding sterically demanding aminopyridine as the starting material. The synthesized complexes could then be alkylated selectively. These complexes were characterized by spectroscopic methods, and their behavior in olefin polymerization and copolymerization of ethene and propene was explored. These mono(aminopyridinato)titanium trichloro complexes are less active if activated with methylaluminoxane (MAO). However, the activity increases strongly if MAO is replaced by d-MAO ("dry methylaluminoxane"). The catalysts show moderate activity toward propene polymerization, while ethylene-propylene copolymers in high-productivity with separated propene units were observed. The catalysts are also highly active in the co- and terpolymerization of 2-ethylidenenorbornene (ENB) with ethylene or ethylene-propylene, together with a very good incorporation of ENB. In all cases, the activity increases with an increase in the steric bulk of the protecting ligand.