Apoptosis-inducing, anti-angiogenic and anti-migratory effects of a dinuclear Pd(II) complex on breast cancer: A promising novel compound.

Because of the high mortality and morbidity rate of breast cancer, successful management of the disease requires synthesis of novel compounds. To this end, ongoing attempts to create new candidates include synthesis of multinuclear metal complexes. The high DNA binding affinity and cytotoxic activity of these complexes makes them promising as breast cancer treatments. This study investigated anti-growth/cytotoxic effect of the dinuclear Pd(II) complex on breast cancer cell lines (MCF-7, MDA-MB-231) using various methods of staining, flow cytometry, and immunoblotting. The study conducted colony formation, invasion, and migration assays were to assess the effect of the complex on metastasis. Increased caspase-3/7 levels and positive annexin V staining were observed in both cell lines, proving apoptosis. Altered TNFR1 and TRADD expression with caspase-8 cleavage followed by BCL-2 inactivation with loss of mitochondrial membrane potential confirmed the presence of apoptosis in MCF-7 and MDA-MB-231, regardless of p53 expression status. The results implied anti-migration properties. Finally, the study used the CAM assay to assess antiangiogenic properties and showed that the complex inhibited angiogenesis. The study concluded the dinuclear Pd(II) complex warrants further in vivo experiments to show its potential in the treatment of breast cancer.

A novel AB3-type trimeric zinc(II)-phthalocyanine as an electrochromic and optical limiting material.

Recent advances in the practical applications of metallophthalocyanines (MPcs) in different technological fields have stimulated us to design and synthesize a new asymmetric AB3-type trimeric zinc(ii)-phthalocyanine (1). This bulky and high molecular weight compound was characterized by elemental analysis, 1H, 13C DEPT, and 1H-1H NOESY NMR, HR MALDI-TOF mass spectrometry, UV-vis, and FT-IR (ATR) techniques. In-depth electrochemical studies show that 1 displays quasi-reversible three one-electron reductions and two one- or two-electron oxidation processes, rather than any redox processes including the transfer of three-electrons in one-step. Besides this, in situ spectroelectrochemical measurements suggest the good application potential of 1 as an electrochromic material in display technologies. A study of the nonlinear optical properties (NLOs) of 1 reveals that the poly(methylmethacrylate) (PMMA) composite film displays a much larger nonlinear absorption coefficient and a lower saturable absorption threshold for optical limiting when compared to the same Pc molecules in solution. Ultrafast transient absorption measurements reveal the intersystem crossing mechanism. Density functional theory (DFT) was used for the geometry optimizations and time dependent-DFT (TD-DFT) for HOMO/LUMO energies and electronic transitions for 1.

Highly Promising Antitumor Agent of a Novel Platinum(II) Complex Bearing a Tetradentate Chelating Ligand.

A new mononuclear cationic platinum(II) coordination compound with 6,6'-bis(NH-benzimidazol-2-yl)-2,2'-bipyridine (L) ligand having N4-tetradentate binding pocket [Pt(L)]Cl2·2H2O (Complex 1) was synthesized and characterized by FT-IR(ATR), UV-vis, 1H NMR, APCI and MALDI MS, and CHN analysis. The antigrowth effect of Complex 1 was tested in breast cancer (MDA-MB-231), lung cancer (A549), colorectal cancer (HCT-116), prostate cancer (PC-3) cell lines, and bronchial epithelial cell line (BEAS-2B) by the SRB and ATP cell viability assays. Apoptosis was detected with Annexin V, mitopotential, BCL-2 inactivation, and γH2AX assays by flow cytometry. Complex 1 was found to have cytotoxic activity of MDA-MB-231, A549, HCT-116, and PC-3 cancer cell lines in a dose-dependent manner for 48 h. Complex 1 has been found to cause cell death through different mechanisms depending on the type of cancer. The findings indicated that complex induced intrinsic apoptosis with the increased mitochondrial membrane depolarization level, Bcl-2 inactivation, and DNA damage in PC-3 and A549 cell lines.

The comparative study of the DNA binding and biological activities of the quaternized dicnq as a dicationic form and its platinum(II) heteroleptic cationic complex.

The square-planar heteroleptic Pt(II) coordination compound [Pt(bpy)(dicnq)](NO3)2 (1) and the quaternized dicnq ligand, namely 12,13-dicyano-5,6-dihydrodipyrazino[2,3-f:1',2',3',4'-lmn][1,10]phenanthroline-4,7-diium dibromide (2) (Fig. 1) were synthesized and fully characterized by means of FTIR, NMR, MALDI-TOF MS and the purity was confirmed by CHN analyses. The DNA binding profiles of 1 and 2 were identified in an identical condition. The biological activities of these compounds were investigated by the assays of transcription and replication inhibition, cytotoxic and antimicrobial activity. The result of this study indicates that, both compounds strongly bind to DNA via intercalation but only 1 has a strong nuclease activity. The coordination compound of dicnq (1) binds to the DNA only slightly stronger than the quaternized form of dicnq (2), and is more potent as an inhibitor of transcription and replication and therefore, 1 has more potential as an anticancer agent but the compounds did not show cytotoxic activity against MCF-7 and MDA-MB-231 breast cancer, and DLD-1 colon cancer cell lines it was found that they only had activities against HepG2 liver cancer cell line with following IC50 values; 94.75 and 159.60 µM for 1 and 2, respectively. In addition, tested bacteria are more susceptible to compound 1. These biological activities of 1 may strongly be due to its ability to digest DNA as a chemical nuclease. According to this study, the quaternization of the ligand does not make biologically more active than the coordination compound of the same ligand in this case. The compound (1) is worth further investigation for its antitumor activities.

Syntheses and studies of electron/energy transfer of new dyads based on an unsymmetrical perylene diimide incorporating chelating 1,10-phenanthroline and its corresponding square-planar complexes with dichloroplatinum(ii) and dichloropalladium(ii ).

Perylene diimides (PDIs) are among the most versatile and functional dyes for supramolecular structures displaying characteristic high absorptions and photo-luminescence properties as the prerequisite for optoelectronic thin film devices. Despite intense investigations into these semi-conducting and electro-active materials, details of their electronic structure are still under examination. In particular, non-planar twisted PDIs as an electron acceptor is a promising model system for efficient charge generation and transport processes. Therefore, a new dyad, an unsymmetrical PDI, N'-(2-ethylhexyl)-N'-(1,10-phenanthroline)-1,6,7,12-tetrakis-(4-methoxyphenoxy)-3,4,9,10-tetracarboxylic acid diimide (1) and its corresponding dichloroplatinum(ii) and dichloropalladium(ii) complexes as new dyads, [(Cl2)M(ii)-(1)] where, M(ii) = Pt(ii) (2) and Pd(ii) (3), were prepared. These dyads were fully characterized by FT-IR, 1D-NMR (1H-NMR and 13C-NMR), 2D-NMR (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC), MALDI TOF mass and UV-Vis spectroscopy. Electronic structure calculations have been employed based on Time-Dependent Density Functional Theory (TDDFT) calculations for the geometry-optimized electronic ground state structures in the gas phase and in dichloromethane (DCM). Current results indicate that 2 and 3 have similar HOMO-LUMO energy gaps which are smaller than 1. The energy and charge transfer processes with molecular structures are crucial for the design of future functional dyads based on donor and acceptor moieties for hybrid optoelectronic devices. Charge transfer mechanisms were also investigated with linear absorption, fluorescence and ultrafast transient absorption spectra for the newly synthesized compounds in DCM. The observed ultrafast intramolecular charge transfer from donor units on the PDI-2 compound is related to fluorescence quenching and faster singlet decay on transient measurements.

Spectroscopic, electrochemical and photovoltaic properties of Pt(ii) and Pd(ii) complexes of a chelating 1,10-phenanthroline appended perylene diimide.

In this study, a bis-chelating bridging perylene diimide ditopic ligand, namely N,N'-di(1,10-phenanthroline)-1,6,7,12-tetrakis-(4-methoxyphenoxy)perylene tetracarboxylic acid diimide (1), was synthesized and characterized. Further reactions of 1 with d8 metal ions such as Pt(ii) and Pd(ii) having preferential square-planar geometry afforded the novel triads [(Cl2)M(ii)-(1)-M(ii)(Cl2)] where M(ii) = Pt(ii) (2), and Pd(ii) (3), respectively. The isolated triads and the key precursor were fully characterized by FT-IR, 1D-NMR (1H NMR and 13C DEPT NMR), 2D-NMR (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC), MALDI-TOF mass and UV/Vis spectroscopy. The electrochemical properties of 1, 2 and 3 were investigated by cyclic voltammetry as well as in situ spectroelectrochemistry and also in situ electrocolorimetric measurements. These compounds were shown to exhibit net colour changes suitable for electrochromic applications. The compounds exhibited remarkably narrow HOMO-LUMO gaps, leading to their ease of reduction at low negative potentials. More importantly, dye-sensitized solar cells (DSSCs) were also fabricated using 1-3 to clarify the potential use of these complexes as a sensitizer. Analysis of the experimental data indicated that 2 has good potential as a sensitizer material for DSSCs.

DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)](2+) and [Pt(bpy)(miip)](2.).

Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)2 (1) and [Pt(bpy)(miip)](PF6)2·2H2O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, (1)H NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K b = 3.55 ± 0.6 × 10(4) M(-1) and 7.01 ± 0.9 × 10(4) M(-1) for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.

A conformationally stressed novel ball-type perylenediimide appended zinc(II)phthalocyanine hybrid: spectroelectrochemical, electrocolorimetric and photovoltaic properties.

A supramolecule, 6, based on an electron-donor zinc phthalocyanine (ZnPc) and an electron-acceptor perylene diimide (PDI) has been synthesized and characterized by elemental analysis, UV/Vis, IR, (1)H NMR and solid state (13)C CPMAS NMR and also MALDI-TOF and ICP mass spectrometry. The PDI appended ZnPc core brings about a geometrical constraint in the molecule with intriguing spectroscopic, electrochemical and photovoltaic properties. The first reduction process of 6 occurs on the PDI core while the first oxidation takes place on the Pc ring. These processes reflect a considerably small HOMO-LUMO gap of 1.50 eV, which has vital importance for optoelectronic applications. In addition, the PDI-based first and second reduction processes of 6 are accompanied by an electrochromic behaviour with colour changes from dark purple to blue and blue to turquoise, respectively. A photovoltaic cell involving 6 as the donor and [6,6]-phenyl C61 butyric acid methyl ester as the acceptor has been fabricated. The measurements of the effect of annealing temperature on its performance indicated that the annealing process gives rise to a significant increase in the open circuit voltage, the fill factor and the photoconversion efficiency.

Synthesis, characterization, oxygen electrocatalysis and OFET properties of novel mono- and ball-type metallophthalocyanines.

Novel mono- and ball-type Co(ii), Zn(ii) and Cu(ii) metallophthalocyanines (MPcs) were synthesized from 1,1'-p-anisylidenbis(2-naphthoxyphthalonitrile). The MPcs have been characterized by elemental analysis, UV/Vis, IR and (1)H-NMR spectroscopy and MALDI-TOF mass spectrometry. The performances of organic field effect transistors (OFETs) of the dinuclear ball-type MPcs have been compared to those of mononuclear counterparts. The ball-type MPc based OFETs showed a p-channel and typical ambipolar transport properties. On the other hand, it was not possible to measure the full transfer characteristics of the mononuclear MPc based devices. The best results were obtained in the case of dinuclear Cu2Pc2. In this case, the mobility value is µ = 4.4 × 10(-2) cm(2) V(-1) s(-1) and the threshold voltage is 27.6 volts. The reduction and oxidation characteristics of the mono-nuclear and ball-type MPcs have been compared by cyclic voltammetry, square wave voltammetry and controlled potential coulometry on platinum in nonaqueous media. The comparison suggested that the ball-type complexes form ring-based and/or metal-based mixed-valence species as a result of the remarkable interaction between the two Pc rings and/or metal centers. The stability of these species was confirmed by the mixed-valence splitting values for the complexes. The electrocatalytic performances of the mononuclear and dinuclear complexes for the oxygen reduction reaction were also studied. The compounds involving Co(ii) at the phthalocyanine core, especially the ball-type one, showed much higher catalytic performances towards oxygen reduction than those of the other ones.

Synthesis, characterization, and DNA binding of complexes [Pt(bpy)(pip)](2+) and [Pt(bpy)(hpip)] (2+).

Two new platinum(II) complexes, [Pt(bpy)(pip)](NO3)2 (1) and [Pt(bpy)(hpip)](NO3)2·2H2O (2) (bpy is 2,2'-bypyridine; pip is 2-phenylimidazo[4,5-f][1,10]phenanthroline; hpip is 2-(2-hydroxyphenyl) imidazo[4,5-f][1,10]phenanthroline), have been synthesized and fully characterized by CHN analysis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, (1)H-NMR spectroscopy, IR spectroscopy (attenuated total reflection), and UV-vis spectroscopy. The DNA-binding behaviors of both complexes have been studied by spectroscopic methods and viscosity measurements, and their ability to inhibit DNA transcription was measured. The results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants of (2.88 ± 0.4) × 10(4) and (5.38 ± 0.8) × 10(4) for 1 and 2, respectively. The comparatively observed difference in the DNA-binding affinities of the two complexes can be reasonably explained by the presence of intramolecular hydrogen bonding between the ortho phenolic group and the nitrogen atom of the imidazole ring. The extended coplanarity of the hpip ligand due to intramolecular hydrogen bonding may lead to an enhancement of the DNA-binding affinity of the hpip complex. In addition, the complexes can promote photocleavage of pUC19 DNA on irradiation as revealed by the spectroscopic and viscometric measurements, with 2 promoting cleavage of pUC19 DNA at lower concentration. Moreover, increasing concentrations of both complexes inhibited DNA transcription, and as expected 2 was shown to be a better antitumor agent than 1.

Synthesis, interface (Au/M2Pc2/p-Si), electrochemical and electrocatalytic properties of novel ball-type phthalocyanines.

The phthalodinitrile derivative (3) was prepared by the reaction of 4,4'-(octahydro-4,7-methano-5H-inden-5-ylidene)bisphenol (1) and 4-nitrophthalonitrile (2) with dry DMF as the solvent in the presence of the base K(2)CO(3) by the method of nucleophilic substitution of an activated nitro group in an aromatic ring. The template reaction of 3 with the corresponding metal salts gave the novel bi-nuclear ball-type metallophthalocyanines, MPcs {M = Co (4), Cu (5), Zn (6)}. Newly synthesized compounds were characterized by elemental analysis, UV-vis, FT-IR (ATR), MALDI-TOF mass and (1)H-NMR spectroscopy techniques. The electronic spectra exhibit an intense π→π* transition of characteristic Q and B bands of the Pc core. The dielectric properties and interface between the spin coated films of 4-6 and a p-type silicon substrate have been studied by fabricating metal-insulator-semiconductor capacitors. The results indicated that the frequency dependence of the dielectric permittivity, ε'(ω), exhibits non-Debye type relaxation for all the temperatures investigated. The ac conductivity results indicated that the conduction mechanism can be explained by a hopping model at low temperatures (<430 K) and a free band conduction mechanism at high temperatures (≥430 K). The density of interface state calculations on these novel compounds showed that the combination of Au/4/p-Si is a promising structure with a high dielectric constant and a low interface trap density suitable for metal-oxide-semiconductor devices. The electrochemical properties of the Pc complexes were examined by cyclic voltammetry, differential voltammetry and controlled potential coulometry on platinum in non-aqueous media. The complexes showed ring-based and/or metal-based mixed-valence behaviours as a result of the remarkable interaction between the two Pc rings and/or metal centres. The mixed-valence splitting values for the complexes suggested that the mixed valence species are considerably stable. The Vulcan XC-72(VC)/Nafion(Nf)/4 modified glassy carbon electrode showed much a higher catalytic performance towards oxygen reduction than those of VC/Nf/5 and VC/Nf/6 modified ones.

1-[6-(6-Acetyl-pyridin-2-yl)pyridin-2-yl]ethanone.

In the title compound, C(14)H(12)N(2)O(2), the asymmetric unit comprises one half-mol-ecule with an inversion center between the pyridine rings. The rings are trans coplanar with the acetyl groups deviating slightly from the mean planes, making a dihedral angle of 4.63 (4)°. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, forming a supra-molecular sheet parallel to (100).

{N,N'-Bis[1-(2-pyrid-yl)ethyl-idene]ethane-1,2-diamine-κN,N',N'',N'''}bis-(trifluoro-methane-sulfanato-κO)copper(II).

A discrete neutral Cu(II) complex, [Cu(CF(3)SO(3))(2)(C(16)H(18)N(4))], has been derived from the symmetrical tetra-dentate Schiff base, N,N'-bis-[1-(pyridin-2-yl)ethyl-idene]ethane-1,2-diamine. The copper centre assumes a tetra-gonally distorted pseudo-octa-hedral geometry with the O atoms of two trifluoro-methane-sulfonate anions coordinated weakly in the axial positions. The Cu-N distances lie in the range 1.941 (3)-2.011 (3) Šand the Cu-O distances are 2.474 (3) and 2.564 (3) Å.

trans-Diaquabis(6-hydroxypicolinato-kappa2N,O2)copper(II).

In the title compound, [Cu(C6H4NO3)2(H2O)2], the Cu(II) ion lies on an inversion centre and has an elongated octahedral environment, equatorially trans-coordinated by two N,O-bidentate picolinate ligands and axially coordinated by two water O atoms. The complex molecules form layers, which are linked by O-H...O hydrogen bonds between the aqua ligands and neighbouring carboxylate groups. An intramolecular hydrogen bond between the coordinated carboxylate O atom and the hydroxy H atom is also observed.

N,N'-bis[1-(pyrazin-2-yl)ethylidene]hydrazine.

Molecules of the title compound, C12H12N6, contain both a diimine linkage and an N-N bond, and assume a planar structure. The compound lies about an inversion centre and there are three intramolecular C-H...N hydrogen bonds.