Novel palladium complexes, KHPd(obap)2·3H2O (3) with oxamido-N-aminopropyl-N'-benzoic acid and Pd(apox) (4) with N,N'-bis(3-aminopropyl)ethanediamide, were synthesized. Exhaustive synthetic, solution ...and structural studies of the two Pd(ii) complexes are reported. The binary and ternary systems of the Pd(ii) ion with H2apox or H3obap as primary ligands and nucleosides (Ado or Cyt) as secondary ligands, are investigated in order to better understand their equilibrium chemistry. The relative stabilities of the ternary complexes are determined and compared with those of the corresponding binary complexes in terms of their Δlog K values. The species distribution of all complexes in solution is evaluated. Fluorescence spectroscopy data shows that the fluorescence quenching of HSA is a result of the formation of the PdL-HSA complex. The structure of complex 3 is confirmed using X-ray crystallography. The results are compared to those obtained for palladium complexes of similar structures. Density functional theory (DFT) has been applied for modelling and energetic analysis purposes. The nature of the Pd-N(O) bond interaction is analyzed using NBO. We report here docking simulation experiments in order to predict the most probable mechanism of pro-drug-action. The next free binding energy order of the best scores from the PdL-DNA docking simulations, cis-Pt(NH3)2(H2O)2(2+) > Pd(obap) > Pd(mda), has been observed in the case of DNA alteration. For the ER and cytosolic stress mechanisms the results of the docking simulations to the chaperons Grp78 and Hsc70 are promising for possible applications as potent protein inhibitors (Ki of Pd(mda)/GRP78 being ∼66 μM and Ki for Pd(obap)/HSC70 being 14.39 μM).
The results of the study of the influence of a static magnetic field of 55 ± 3 mT on the growth rates of diamagnetic sodium chlorate crystals in the direction ⟨100⟩ will be presented. Two groups of ...experiments were performed in the same solution supersaturation range of 0.89–1.78%, the first in zero field conditions, and the second in an applied magnetic field. The results show that crystals nucleated and grown in a static magnetic field have higher mean growth rates in the ⟨100⟩ direction than crystals in a zero field. Also, X-ray analyses suggest that crystals nucleated and grown in a magnetic field may have a higher lattice constant. Possible mechanisms and possible reasons for these phenomena are discussed.
Two novel rhodium(III) complexes, namely, RhIII(X)Cl3 (X = 2 2,6-bis((4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine or ...2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine), were synthesized from camphor derivatives of a bis(pyrazolylpyridine), tridentate nitrogen-donor chelate system, giving RhIII(H2L*)Cl3 (1a) and RhIII(Me2L*)Cl3 (1b). A rhodium(III) terpyridine (terpy) ligand complex, RhIII(terpy)Cl3 (1c), was also synthesized. By single-crystal X-ray analysis, 1b crystallizes in an orthorhombic P212121 system, with two molecules in the asymmetric unit. Tridentate coordination by the N,N,N-donor localizes the central nitrogen atom close to the rhodium(III) center. Compounds 1a and 1b were reactive toward l-methionine (l-Met), guanosine-5′-monophosphate (5′-GMP), and glutathione (GSH), with an order of reactivity of 5′-GMP > GSH > l-Met. The order of reactivity of the RhIII complexes was: 1b> 1a > 1c. The RhIII complexes showed affinity for calf thymus DNA and bovine serum albumin by UV–vis and emission spectral studies. Furthermore, 1b showed significant in vitro cytotoxicity against human epithelial colorectal carcinoma cells. Since the RhIII complexes have similar coordination modes, stability differences were evaluated by density functional theory (DFT) calculations (B3LYP(CPCM)/LANL2DZp). With (H2L*) and (terpy) as model ligands, DFT calculations suggest that both tridentate ligand systems have similar stability. In addition, molecular docking suggests that all test compounds have affinity for the minor groove of DNA, while 1b and 1c have potential for DNA intercalation.
Three new ruthenium(II) complexes were synthesized from different substituted isothiazole ligands 5-(methylamino)-3-pyrrolidine-1-ylisothiazole-4-carbonitrile (1), ...5-(methylamino)-3-(4-methylpiperazine-1-yl)isothiazole-4-carbonitrile (2) and 5-(methylamino)-3-morpholine-4-ylisothiazole-4-carbonitrile (3): Ru(η6-p-cymene)Cl2(L1)·H2O (4), Ru(η6-p-cymene)Cl2(L2) (5) and Ru(η6-p-cymene)Cl2(L3) (6). All complexes were characterized by IR, UV–Vis, NMR spectroscopy, and elemental analysis. The molecular structures of all ligands and complexes 4 and 6 were determined by an X-ray. The results of the interactions of CT-DNA (calf thymus deoxyribonucleic acid) and HSA (human serum albumin) with ruthenium (II) complexes reveal that complex 4 binds well to CT-DNA and HSA. Kinetic and thermodynamic parameters for the reaction between complex and HSA confirmed the associative mode of interaction. The results of Quantum mechanics (QM) modelling and docking experiments toward DNA dodecamer and HSA support the strongest binding of the complex 4 to DNA major groove, as well as its binding to IIa domain of HSA with the lowest ΔG energy, which agrees with the solution studies. The modified GOLD docking results are indicative for Ru(p-cymene)LCl··(HSA··GLU292) binding and GOLD/MOPAC(QM) docking/modelling of DNA/Ligand (Ru(II)-N(7)dG7) covalent binding. The cytotoxic activity of compounds was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. Neither of the tested compounds shows activity against a healthy MRC-5 cell line while the MCF-7 cell line is the most sensitive to all. Compounds 3, 4 and 5 were about two times more active than cisplatin, while the antiproliferative activity of 6 was almost the same as with cisplatin. Flow cytometry analysis showed the apoptotic death of the cells with a cell cycle arrest in the subG1 phase.
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•Three new complexes Ru(ɳ6-p-cymene)Cl2(L) with isothiazole ligands were prepared.•Anticancer activity was evaluated against one healthy and four cancer cell lines.•The interactions with calf thymus DNA and human serum albumin have been studied.•Docking experiments toward human serum albumin and DNA dodecamer have been done.
•Two new disubstituted tetrazoles were synthesized.•Single-crystal X-ray diffraction analysis of both tetrazoles was performed.•HSA and NCI analysis revealed intermolecular interactions in ...crystals.•MEP, global and local (dual descriptor) reactivity indices were calculated.
Herein, we report a synthesis of two new disubstituted tetrazoles, 2-(2,4-dinitrophenyl)-5-methyl-2H-tetrazole (2) and 1-(2,4-dinitrophenyl)-5-methyl-1H-tetrazole (3). The products were characterized by 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. The intermolecular interactions in the crystals were investigated by Hirshfeld surface analysis, 2D fingerprint plots, and noncovalent interaction analysis (NCI). Tetrazole rings of both compounds were found to be involved in both strongest attractive and repulsive intermolecular interactions. DFT calculations were performed using the PW6B95-D3(BJ)/def2-TZVP level of theory in order to obtain information about the molecular electrostatic potential (MEP), and global and local reactivity (dual descriptor) indices of the studied tetrazoles. The calculated molecular electrostatic potentials correlated well with the Hirshfeld surface and NCI plots. The 1,5-disubstituted tetrazole exhibited lower kinetic stability and was slightly more electrophilic than the 2,5-regioisomer. The dual descriptor index was used to reveal electrophilic and nucleophilic sites for both molecules.
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Newly palladium(II) complexes (C1, C2) with derivatives of 2-aminothiazoles (L1 = 2-amino-6-methylbenzothiazole, L2 = 2-amino-6-chlorobenzothiazole), general formula PdL2Cl2 were synthesized and ...characterized by elemental microanalyses, IR, NMR spectroscopy and X-ray spectroscopy in case of Pd(L2)2Cl2. The kinetic of the substitution reactions of complexes and the nucleophiles, such as guanosine-5′-monophosphate (5’-GMP), tripeptide glutathione (GSH) and amino acid L-methionine (L-Met), were studied by stopped-flow technique. The complex C2 was always more reactive, while the order of the reactivity of the nucleophiles, due to the associative mode of the reaction, was L-Met > GSH > 5’-GMP. In order to determine the type of interactions between palladium(II) complexes and calf thymus DNA (CT-DNA), we used electronic absorption spectroscopy, viscosity measurements, and fluorescence spectroscopic studies, while interactions with bovine serum albumin (BSA) were determined only with fluorescence spectroscopic studies. The observed results confirmed that both complexes bound to DNA by groove binding. The significantly strong interaction with BSA, especially for complex C2, was also observed. In vitro cytotoxic activity was evaluated against four tumor cell lines, 4 T1, CT26, MDA-MB-468, HCT116 and mesenchymal stem cells (mMSC). C1 complex showed higher cytotoxic activity against CT26 cell line. Flow cytometry analysis showed that C1 stimulated apoptosis of tumor cells via inhibition of expression of antiapoptotic Bcl-2 molecule and decelerated proliferation by decreasing Cyclin-D and increasing expression of P21. In vitro antimicrobial activity for ligands and corresponding palladium(II) complexes was investigated by microdilution method and minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) were determined. Tested compounds exhibited selective and moderate activity.
Newly complexes PdL2Cl2 (L1 = 2-amino-6-methylbenzothiazole, L2 = 2-amino-6-chlorobenzothiazole) were synthesized and characterized by elemental microanalysis, IR, 1H, 13C NMR and X-ray spectroscopy for Pd(L2)2Cl2. The kinetic of the substitution reactions and interactions of complexes with calf thymus DNA and bovine serum albumin were determined. In vitro cytotoxic and antimicrobial activity were tested. Display omitted
•Two new palladium(II) complexes were synthesized.•Characterization was performed by IR, 1H and 13C NMR and X-ray spectroscopy.•The kinetic of the substitution reactions were studied by stopped-flow technique.•The interactions of new complexes with calf thymus DNA and bovine serum albumin were investigated.•Cytotoxic and antimicrobial activities of palladium(II) complexes were evaluated.
Four silver-based coordination polymers, {Ag(L)2(BF4)}∞ (1), {Ag(H2BTC)(L)·(H3BTC)}∞ (2), {Ag2(H2BTEC)(L)2·3.33H2O}∞ (3), and Ag(H25SSA)(L)∞ (4), were synthesized using ...thiomorpholine-4-carbonitrile (L) as the primary ligand and three aromatic polyoxoacids as coligands: trimesic (H3BTC), pyromellitic (H4BTEC), and 5-sulfosalicylic acid (H35SSA). Compounds 1 and 3 are two-dimensional, while 2 and 4 are one-dimensional. L acts as a bis-monodentate ligand, while the Ag(I) ion is three-coordinated in 2 and four-coordinated in all of the other compounds. The tetrahedral coordination of Ag(I) in 3 leads to an almost complete absence of intermolecular interactions with the metal center. All compounds show reasonable photocatalytic activity for photocatalytic degradation of mordant blue 9 dye, with reaction rates in the 0.036–0.056 min–1 range. Changes in the reaction rates can be correlated with the type and coordination of the coligand. Complex 3 exhibits photoluminescence at 77 K, while 4 exhibits photoluminescence at both room temperature and 77 K. Luminescence lifetimes indicate electronic transitions of singlet parentage, where transitions are allowed. A TD-DFT study determined the contributions of individual singlet–singlet electronic excitations to the fluorescence, indicating that metal– intraligand transitions are responsible for luminescence in both complexes.
•The 3-acetyl-4‑hydroxy‑2-oxo-2H-chromen-7-yl acetate (3AcHyC) was synthesized and characterized.•The crystallographic structure of the 3AcHyC was analyzed.•The hirshfeld surface analysis of 3AcHyC ...was performed.•The electronic structure of 3AcHyC was examined using a quantum chemical approach.•The inhibitory nature of 3AcHyC against the TDP1 receptor was investigated by molecular docking.
In the present study, the structural, spectroscopic (FT-IR, NMR, and UV–Vis) and electronic properties of newly synthesized 3-acetyl-4‑hydroxy‑2-oxo-2H-chromen-7-yl acetate (3AcHyC) were determined by experimental and theoretical methods. The structural parameters (bond lengths and angles) were calculated using the B3LYP-D3BJ/6–311++G(d,p) theoretical model and compared with the experimentally determined crystal structure of the investigated compound. Hirshfeld surfaces and fingerprint plots analysis were used to find and analyze the percentage of intermolecular interactions in the crystal structure of the investigated compound. The calculated FT-IR frequencies were determined from the same theoretical model and matched with experimental data. The NMR chemical shifts (1H and 13C) were recorded in the CDCl3 solution and compared with theoretically determined spectra. The UV–Vis absorption spectrum was analyzed and compared with the spectrum calculated by Time-Dependent Density Functional Theory (TD-DFT). The obtained and compared spectroscopic data demonstrated that applied level theory reproduces well the experimental results. Furthermore, to examine the electronic structure of the studied molecule, the Natural Bond Orbitals (NBOs), the Quantum Theory of Atoms in Molecules (QTAIM), Non-linear Optical parameter (NLO), and Mapped Molecular Electrostatic Potential (MEP) surface analyses were also performed with the same level of theory. Furthermore, results of in silico molecular docking calculations, indicate the stability as well as favorable binding interactions between the investigated compound and the Tyrosyl DNA-Phosphodiesterase 1 (TDP1) active site. Also, the results indicate that the investigated compound is a favorable precursor in the synthesis of new coumarin derivatives with potentially significant biological and pharmacological properties.
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In this study, we have developed a series of new monofunctional Ru(II) complexes of the general formula mer-Ru(Cl-Ph-tpy)(N-N)ClCl in which Cl-Ph-tpy is 4′-(4-chlorophenyl)-2,2′:6′,2″-terpyridine, ...N-N is a bidentate chelating ligand (1,2-diaminoethane (en, 1), 1,2-diaminocyclohexane (dach, 2) or 2,2′-bipyridine (bpy, 3)). All complexes were fully characterized by elemental analysis and spectroscopic techniques (IR, UV–Vis, 1D and 2D NMR). Their chemical behavior in aqueous solution was studied by UV–Vis and NMR spectroscopy showing that all compounds are relatively labile leading to the formation of the corresponding aqua species 1aq–3aq. Their DNA binding ability was evaluated by UV–Vis spectroscopy, fluorescence quenching measurements and viscosity measurements. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (Ksv=1.1–2.7×104M−1). These experiments show that the ruthenium complexes interact with DNA via intercalation. The complexes bind to serum protein albumin displaying relatively high binding constants (Ksv=104–105M−1). Compound 3 displayed from high to moderate cytotoxicity against two cancer cell lines HeLa and A549 (with IC50ca. 12.7μM and 53.8μM, respectively), while complexes 1 and 2 showed only moderate cytotoxicity (with IC50ca. 84.8μM and 96.3μM, respectively) against HeLa cells. The cell cycle analysis (by flow cytometry) of HeLa and A549 cells treated with complex 3 shows minor changes on the cell cycle phase distribution.
A series of new ruthenium(II)-chlorophenyl-terpyridine complexes were synthesized and fully characterized. The chlorido complexes proved to be labile in aqueous solution and capable of interacting with biomolecules. Furthermore, the complex with bidentate aromatic diamine proved to be superior to those with aliphatic diamines in terms of lipophilicity and biological activity. Display omitted
•Synthesis of new Ru(II) polypyridyl complexes with chlorophenyl-terpyridine ligand.•All complexes in aqueous solution release the Cl− ligand to form the aqua species.•Ruthenium complexes show good binding affinity to DNA and bovine serum albumin.•The complex with bidentate aromatic diamine displays the highest cytotoxicity.
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