Spectroscopic investigation into the interaction of a diazacyclam-based macrocyclic copper(ii) complex with bovine serum albumin.

Cyclam-based ligands and their complexes are known to show antitumor activity. This study was undertaken to examine the interaction of a diazacyclam-based macrocyclic copper(II) complex with bovine serum albumin (BSA) under physiological conditions. The interactions of different metal-based drugs with blood proteins, especially those with serum albumin, may affect the concentration and deactivation of metal drugs, and thereby influence their availability and toxicity during chemotherapy. In this vein, several spectral methods including UV-vis absorption, fluorescence and circular dichroism (CD) spectroscopy techniques were used. Spectroscopic analysis of the fluorescence quenching confirmed that the Cu(II) complex quenched BSA fluorescence intensity by a dynamic mechanism. In order to further determine the quenching mechanism, an analysis of Stern-Volmer plots at various concentrations of BSA was carried out. It was found that the KSV value increased with the BSA concentration. It was suggested that the fluorescence quenching process was a dynamic quenching rather than a static quenching mechanism. Based on Förster's theory, the average binding distance between the Cu(II) complex and BSA (r) was found to be 4.98 nm; as the binding distance was less than 8 nm, energy transfer from BSA to the Cu(II) complex had a high possibility of occurrence. Thermodynamic parameters (positive ΔH and ΔS values) and measurement of competitive fluorescence with 1-anilinonaphthalene-8-sulphonic acid (1,8-ANS) indicated that hydrophobic interaction plays a major role in the Cu(II) complex interaction with BSA. A Job's plot of the results confirmed that there was one binding site in BSA for the Cu(II) complex (1:1 stoichiometry). The site marker competitive experiment confirmed that the Cu(II) complex was located in site I (subdomain IIA) of BSA. Finally, CD data indicated that interaction of the Cu(II) complex with BSA caused a small increase in the α-helical content. Copyright © 2016 John Wiley & Sons, Ltd.

Coordination of a triazine ligand with CuII and AgI investigated by spectral, structural, theoretical and docking studies.

Two complexes of 5-phenyl-3-(pyridin-2-yl)-1,2,4-triazine (PPTA), namely (ethanol-κO)bis(nitrato-κO)[5-phenyl-3-(pyridin-2-yl-κN)-1,2,4-triazine-κN2]copper(II), [Cu(NO3)2(C14H10N4)(C2H6O)] or [Cu(NO3)2(PPTA)(EtOH)] (1), and bis[µ-5-phenyl-3-(pyridin-2-yl)-1,2,4-triazine]-κ3N1:N2,N3;κ3N2,N3:N1-bis[(nitrato-κO)silver(I)], [Ag2(NO3)2(C14H10N4)2] or [Ag2(NO3)2(µ-PPTA)2] (2), were prepared and characterized by elemental analysis, FT-IR spectroscopy and single-crystal X-ray diffraction. The X-ray structure analysis of 1 revealed a copper complex with square-pyramdial geometry containing two O-donor nitrate ligands along with an N,N'-donor PPTA ligand and one O-donor ethanol ligand. In the binuclear structure of 2, formed by the bridging of two PPTA ligands, each Ag atom has an AgN3O environment and square-planar geometry. In addition to the four dative interactions, each Ag atom interacts with two O atoms of two nitrate ligands on adjacent complexes to complete a pseudo-octahedral geometry. Density functional theory (DFT) calculations revealed that the geometry around the Cu and Ag atoms in 1opt and 2opt (opt is optimized) for an isolated molecule is the same as the experimental results. In 1, O-H...O hydrogen bonds form R12(4) motifs. In the crystal network of the complexes, in addition to the hydrogen bonds, there are π-π stacking interactions between the aromatic rings (phenyl, pyridine and triazine) of the ligands on adjacent complexes. The ability of the ligand and complexes 1 and 2 to interact with ten selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) was investigated by docking studies. The results show that the studied compounds can interact with proteins better than doxorubicin (except for TrxR and Top II).

Spectral, structural and theoretical study of the effects of thiocyanato and dicyanamido ligands on the geometry of PbII complexes containing a triazinic ligand.

Two lead(II) complexes of 5,6-bis(furan-2-yl)-3-(pyridin-2-yl)-1,2,4-triazine (DFPT), namely one-dimensional (1D) catena-poly[[bis[5,6-bis(furan-2-yl)-3-(pyridin-2-yl-κN)-1,2,4-triazine-κN2]lead(II)]-di-µ-thiocyanato-κ2N:S;κ2S:N], [Pb(NCS)2(C16H10N4O2)2]n, 1, and binuclear di-µ-dicyanamido-κ2N1:N5;κ2N5:N1-bis{[5,6-bis(furan-2-yl)-3-(pyridin-2-yl-κN)-1,2,4-triazine-κN2](nitrato-κ2O,O')lead(II)}, [Pb2(C2N3)2(NO3)2(C16H10N4O2)4], 2, as well as DFPT itself, were prepared and identified by elemental analysis, FT-IR, 1H NMR spectroscopy and single-crystal X-ray structural analyses. In the double-chain 1D coordination polymer of 1 and the binuclear structure of 2, the Pb atom has a hemidirected-PbN6S2 and a rare holodirected-PbN6O2 environment, respectively, with a distorted cubic geometry. All the coordination modes of dicyanamide ligands within lead complexes were studied using the Cambridge Structural Database (CSD) to compare them with the structures of 1 and 2. In addition to hydrogen bonds, the crystal networks are stabilized by π-π stacking interactions between the triazine, furyl and pyridine aromatic rings. The most stable theoretical structures of the title compounds predicted by density functional theory (DFT) calculations were compared with the solid-state results.

Reaction of 2-[(2-aminoethyl)amino]ethanol with pyridine-2-carbaldehyde and complexation of the products with CuII and CdII along with docking studies.

The reaction between 2-[2-(aminoethyl)amino]ethanol and pyridine-2-carbaldehyde in a 1:2 molar ratio affords a mixture containing 2-({2-[(pyridin-2-ylmethylidene)amino]ethyl}amino)ethanol (PMAE) and 2-[2-(pyridin-2-yl)oxazolidin-3-yl]-N-(pyridin-2-ylmethylidene)ethanamine (POPME). Treatment of this mixture with copper(II) chloride or cadmium(II) chloride gave trichlorido[(2-hydroxyethyl)({2-[(pyridin-2-ylmethylidene)amino]ethyl})azanium]copper(II) monohydrate, [Cu(C10H16N3O)Cl3]·H2O or [Cu(HPMAE)Cl3]·H2O, 1, and dichlorido{2-[2-(pyridin-2-yl)oxazolidin-3-yl]-N-(pyridin-2-ylmethylidene)ethanamine}cadmium(II), [CdCl2(C16H18N4O)] or [CdCl2(POPME)], 2, which were characterized by elemental analysis, FT-IR, Raman and 1H NMR spectroscopy and single-crystal X-ray diffraction. PMAE is potentially a tetradentate N3O-donor ligand but coordinates to copper here as an N2 donor. In the structure of 1, the geometry around the Cu atom is distorted square pyramidal. In 2, the Cd atom has a distorted octahedral geometry. In addition to the hydrogen bonds, there are π-π stacking interactions between the pyridine rings in the crystal packing of 1 and 2. The ability of PMAE, POPME and 1 to interact with ten selected biomolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS, Top II and B-DNA) was investigated by docking studies and compared with doxorubicin.

Investigation of the effect of the N-oxidation process on the interaction of selected pyridine compounds with biomacromolecules: structural, spectral, theoretical and docking studies.

Two new N-oxide compounds, namely glycinium 2-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-6-carboxylate-glycine-water (1/1/1), C2H6NO2+·C7H4NO5-·C2H5NO2·H2O or [(2,6-HpydcO)(HGLY)(GLY)(H2O)], 1, and methyl 6-carboxy-1-(λ1-oxidaneyl)-1λ4-pyridine-2-carboxylate, C8H7NO5 or 2,6-HMepydcO, 2, were prepared and identified by elemental analysis, FT-IR, Raman spectroscopy and single-crystal X-ray diffraction. The X-ray analysis of 1 revealed an ionic compound containing a 2,6-HpydcO- anion, a glycinium cation, a neutral glycine molecule and a water molecule. Compound 2 is a neutral compound with two independent units in its crystal structure. In addition to the hydrogen bonds, the crystal network is stabilized by π-π stacking interactions of the types pyridine-carboxylate and carboxylate-carboxylate. The thermodynamic stability and charge-distribution patterns for isolated molecules of 2,6-H2pydcO and 2,6-HMepydcO, and their two similar derivatives, pyridine-2,6-dicarboxylic acid (2,6-H2pydc) and dimethyl 1-(λ1-oxidaneyl)-1λ4-pyridine-2,6-dicarboxylate (2,6-Me2pydcO), were studied by density functional theory (DFT) and natural bond orbital (NBO) analysis, respectively. The ability of these compounds and their analogues to interact with nine selected biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) was investigated using docking calculations.

Theoretical and experimental investigation of anticancer activities of an acyclic and symmetrical compartmental Schiff base ligand and its Co(ii), Cu(ii) and Zn(ii) complexes.

A compartmental Schiff base ligand, 2,2'-((((((2-hydroxypropane-1,3-diyl)bis(oxy))bis(2,1-phenylene))bis(methylene))bis(azanylylidene))bis(methanylylidene))bis(4-bromophenol) (H3LBr) and its complexes with cobalt(ii), copper(ii) and zinc(ii) including, [Co(HLBr)] (1), [Cu2(LBr)(µ-1,3-OAc)]·MeOH (2) and [Zn(HLBr)] (3) were prepared using template synthesis and characterised by elemental analysis, FT-IR and 1H NMR spectroscopies and single-crystal X-ray diffraction. In the structure of complexes 1 and 3 the metal atom has a MN2O2 environment with tetrahedral geometry while complex 2 has a binuclear structure with a MNO4 environment and square planar geometry around the copper atom. The ability of all compounds to interact with the nine biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) are investigated by docking calculations. For examination of the docking results, the in vitro activities of eight compounds against the human leukemia cell line K562 was investigated by evaluation of IC50 values and mode of cell death (apoptosis).

Anticancer activities of a ß-amino alcohol ligand and nanoparticles of its copper(ii) and zinc(ii) complexes evaluated by experimental and theoretical methods.

2-(2-(2-Hydroxyethylamino)ethylamino)cyclohexanol (HEAC) and copper and zinc complexes, [Cu(HEAC)Cl]Cl (1), [Cu(HEAC)Br]Br (2), [Zn(HEAC)Cl2] (3), were prepared and identified by elemental analysis, FT-IR, UV-Vis, 1H NMR spectroscopy and single-crystal X-ray diffraction. Also nanoparticles of 1-3 were prepared for anticancer studies by ultrasonic irradiation. Particle size and morphology of the nano particles are investigated by PXRD and SEM, respectively. X-ray analysis revealed that the ionic complexes 1 and 2 are isostructural. In the structure of complexes 1 and 2, the metal atom has a CuN2O2X (X: Cl (1), Br (2)) environment with square-pyramidal geometry, containing the tetradentate N2O2-donor HEAC. The bond length of the axial position in the square-pyramidal geometry of 1 and 2 is elongated. Complex 3 has a ZnN2OCl2 environment with trigonal bipyramidal geometry around the zinc atom in which the HEAC acts as mer-N2O-donor. The ability of HEAC and nano particles 1-3 to interact with the nine biomacromolecules (BRAF kinase, CatB, DNA gyrase, HDAC7, rHA, RNR, TrxR, TS and Top II) are investigated by docking calculations. For examination of the docking results, the in vitro activities of four compounds against the human leukemia cell line K562 were investigated by evaluation of IC50 values and mode of cell death (apoptosis). The thermodynamic stability of the compounds along with the charge distribution pattern were studied by DFT and NBO analysis, respectively.