Rachel R. Butorac

Highly luminescent poly(methyl methacrylate)-incorporated europium complex supported by a carbazole-based fluorinated β-diketonate ligand and a 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide co-ligand.

A novel efficient antenna complex of Eu(3+) [Eu(CPFHP)(3)(DDXPO)] supported by a highly fluorinated carbazole-substituted β-diketonate ligand, namely, 1-(9H-carbazol-2-yl)-4,4,5,5,5-pentafluoro-3-hydroxypent-2-en-1-one (CPFHP) and the 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide (DDXPO) ancillary ligand, has been synthesized, structurally characterized, and its photoluminescent behavior examined. The single-crystal X-ray diffraction analysis of Eu(CPFHP)(3)(DDXPO) revealed that this complex is mononuclear, and that the central Eu(3+) ion is surrounded by eight oxygen atoms, six of which are provided by the three bidentate β-diketonate ligands. The remaining two oxygen atoms are furnished by the chelating phosphine oxide ligand. The coordination polyhedron is best described as that of a distorted square antiprism. The photophysical properties of Eu(CPFHP)(3)(DDXPO) benefit from adequate protection of the metal by the ligands with respect to non-radiative deactivation as well as an efficient ligand-to-metal energy transfer process which exceeds 66% in chloroform solution with a quantum yield of 47%. As an integral part of this work, the synthesis, characterization, and luminescent properties of poly(methyl methacrylate) (PMMA) polymer films doped with Eu(CPFHP)(3)(DDXPO) are also reported. The luminescent efficiencies of the doped films (photoluminescence quantum yields 79-84%) are dramatically enhanced in comparison with that of the precursor complex. The new luminescent PMMA-doped Eu(CPFHP)(3)(DDXPO) complex therefore shows considerable promise for polymer light-emitting diode and active polymer optical fiber applications.

Copper(I) and nickel(II) complexes with 1 : 1 vs. 1 : 2 coordination of ferrocenyl hydrazone ligands: Do the geometry and composition of complexes affect DNA binding/cleavage, protein binding, antioxidant and cytotoxic activities?

A new series of geometrically different complexes containing ferrocenyl hydrazone ligands were synthesised by reacting suitable precursor complex [MCl(2)(PPh(3))(2)] with the ligands HL(1) or HL(2) (where M = Cu(II) or Ni(II); HL(1) = [Cp(2)Fe(CH=N-NH-CO-C(6)H(5))] (1) and HL(2) = [Cp(2)Fe(CH=N-NH-CO-C(5)H(4)N)]) (2). The new complexes of the composition [Cu(L(1))(PPh(3))(2)], (3) [Cu(L(2))(PPh(3))(2)] (4), [Ni(L(1))(2)] (5) and [Ni(L(2))(2)] (6) were characterised by various spectral studies. Among them, complexes 3 and 5 characterised by single crystal X-ray diffraction showed a distorted tetrahedral structure for the former with 1:1 metal-ligand stoichiometry, but a distorted square planar geometry with 1:2 metal-ligand stoichiometry in the case of the latter. Systematic biological investigations like DNA binding, DNA cleavage, protein binding, free radical scavenging and cytotoxicity activities were carried out using all the synthesised compounds and the results obtained were explained on the basis of structure-activity relationships. The binding constant (K(b)) values of the synthesised compounds are found to be in the order of magnitude 10(3)-10(5) M(-1) and also they exhibit significant cleavage of supercoiled (SC) pUC19 DNA in the presence of H(2)O(2) as co-oxidant. The conformational changes of bovine serum albumin (BSA) upon binding with the above complexes were also studied. In addition, concentration dependent free radical scavenging potential of all the synthesised compounds (1-6) was also carried out under in vitro conditions. Assays on the cytotoxicity of the above complexes against HeLa and A431 tumor cells and NIH 3T3 normal cells were also carried out.

Effect of substitution and planarity of the ligand on DNA/BSA interaction, free radical scavenging and cytotoxicity of diamagnetic Ni(II) complexes: a systematic investigation.

Four new bivalent nickel hydrazone complexes have been synthesised from the reactions of [NiCl(2)(PPh(3))(2)] with H(2)L {L = dianion of the hydrazones derived from the condensation of salicylaldehyde or o-hydroxy acetophenone with p-toluic acid hydrazide (H(2)L(1)) (1), (H(2)L(2)) (2) and o-hydroxy acetophenone or o-hydroxy naphthaldehyde with benzhydrazide (H(2)L(3)) (3) and (H(2)L(4)) (4)} and formulated as [Ni(L(1))(PPh(3))] (5), [Ni(L(2))(PPh(3))] (6), [Ni(L(3))(PPh(3))] (7) and [Ni(L(4))(PPh(3))] (8). Structural characterization of complexes 5-8 were accomplished by using various physico-chemical techniques. In order to study the influence of substitution in the ligand and its planarity on the biological activity of complexes 5-8 containing them, suitable hydrazone ligands 1-4 have been selected in this study. Single crystal diffraction data of complexes 5, 7 and 8 proved the geometry of the complexes to be distorted square planar with a 1 : 1 ratio between the metal ion and the coordinated hydrazones. To provide more insight on the mode of action of complexes 5-8 under biological conditions, additional experiments involving their interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) were monitored by UV-visible and fluorescence titrations respectively. Further, the ligands 1-4 and corresponding nickel(ii) chelates 5-8 have been tested for their scavenging effect towards OH and O(2)(-) radicals. The effect of complexes 5-8 to arrest the growth of HeLa and Hep-2 tumour cell lines has been studied along with the cell viability against the non-cancerous NIH 3T3 cells under in vitro conditions.

Lanthanide-Based Coordination Polymers Assembled from Derivatives of 3,5-Dihydroxy Benzoates: Syntheses, Crystal Structures, and Photophysical Properties

Two new aromatic carboxylic acids, namely, 3,5-bis(benzyloxy)benzoic acid (HL1) and 3,5-bis(pyridine-2-ylmethoxy)benzoic acid (HL2), have been prepared by replacing the hydroxyl hydrogens of 3,5-dihydroxy benzoic acid with benzyl and pyridyl moieties, respectively. The anions derived from HL1 and HL2 have been used for the support of a series of lanthanide coordination compounds [Eu(3+) = 1-2; Tb(3+) = 3-4; Gd(3+) = 5-6]. The new lanthanide complexes have been characterized on the basis of a variety of spectroscopic techniques in conjunction with an assessment of their photophysical properties. Lanthanide complexes 2, 4, and 6, which were synthesized from 3,5-bis(pyridine-2-ylmethoxy)benzoic acid, were structurally authenticated by single-crystal X-ray diffraction. All three complexes were found to exist as infinite one-dimensional (1-D) coordination polymers with the general formula {[Ln(L2)(3)(H(2)O)(2)]·xH(2)O}(n). Scrutiny of the packing diagrams for 2, 4, and 6 revealed the existence of interesting two-dimensional molecular arrays held together by intermolecular hydrogen-bonding interactions. Furthermore, the coordinated benzoate ligands serve as efficient light harvesting chromophores. In the cases of 1-4, the lowest energy maxima fall in the range 280-340 nm [molar absorption coefficient (ε) = (0.39-1.01) × 10(4) M(-1) cm(-1)]. Moreover, the Tb(3+) complexes 3 and 4 exhibit bright green luminescence efficiencies in the solid state (Φ(overall) = 60% for 3; 27% for 4) and possess longer excited state lifetimes than the other complexes (τ = 1.16 ms for 3; 1.38 ms for 4). In contrast to the foregoing, the Eu(3+) complexes 1 and 2 feature poor luminescence efficiencies.

Variation in the biomolecular interactions of nickel(II) hydrazone complexes upon tuning the hydrazide fragment

Three new bivalent nickel hydrazone complexes have been synthesised from the reactions of [NiCl(2)(PPh(3))(2)] with H(2)L {L = dianion of the hydrazones derived from the condensation of o-hydroxynaphthaldehyde with furoic acid hydrazide (H(2)L(1)) (1)/thiophene-2-acid hydrazide (H(2)L(2)) (2)/isonicotinic acid hydrazide (H(2)L(3)) (3)} and formulated as [Ni(L(1))(PPh(3))] (4), [Ni(L(2))(PPh(3))] (5) and [Ni(L(3))(PPh(3))] (6). Structural characterization of these compounds 4-6 were accomplished by using various physico-chemical techniques. Single crystal X-ray diffraction data of complexes 4 and 5 proved their distorted square planar geometry. In order to ascertain the potential of the above synthesised compounds towards biomolecular interactions, additional experiments involving interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) were carried out. All the ligands and corresponding nickel(ii) chelates have been screened for their scavenging effect towards O(2)(-), OH and NO radicals. The efficiency of complexes 4-6 to arrest the growth of HeLa, HepG-2 and A431 tumour cell lines has been studied along with the cell viability test against the non-cancerous NIH 3T3 cells under in vitro conditions.

Antimicrobial Properties of Some Bis(Iminoacenaphthene (BIAN)-Supported N-Heterocyclic Carbene Complexes of Silver and Gold

The AgCl, AgOAc, AuCl, and AuOAc complexes of the new bis(imino)acenaphthene(BIAN)-supported N-heterocyclic carbene ligand and the precursor imidazolium salt have been investigated with respect to their antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Psudomonas aeruginosa. The most active antimicrobial is the precursor imidazolium salt, which has a minimum inhibitory concentration (MIC) value of <40 μg/mL. The MIC values for the silver complexes IPr(BIAN)AgCl and IPr(BIAN)AgOAc against Gram-positive S. aureus are comparable to that for AgNO3, while those against Gram-negative E. coli and P. aeroginosa are significantly larger. Similar behavior was evident for the gold acetate complex IPr(BIAN)AuOAc. However, in the case of the gold chloride analogue, the MIC values are virtually identical for both the Gram-positive and the Gram-negative bacteria.

Nanofiber composites containing N-heterocyclic carbene complexes with antimicrobial activity.

This report concerns nanofiber composites that incorporate N-heterocyclic carbenes and the use of such composites for testing antimicrobial and antifungal activities. The nanofiber composites were produced by electrospinning mixtures of the gold chloride or gold acetate complexes of a bis(imino)acenaphthene (BIAN)-supported NHC with aqueous solutions of polyvinyl alcohol (PVA). The products were characterized by scanning-electron microscopy, which revealed that nanofibers in the range of 250–300 nm had been produced. The biological activities of the nanofiber composites were tested against two Gram-positive bacteria, six Gram-negative bacteria, and two fungal strains. No activity was evident against the fungal strains. However, the gold chloride complex was found to be active against all the Gram-positive pathogens and one of the Gram-negative pathogens. It was also found that the activity of the produced nanofibers was localized and that no release of the bioactive compound from the nanofibers was evident. The demonstrated antimicrobial activities of these novel nanofiber composites render them potentially useful as wound dressings.

Syntheses, Structures and Antimicrobial Activities of bis(Imino)acenaphthene (BIAN) Imidazolium Salts

The syntheses of four new bis(imino)acenaphthene (BIAN) imidazolium chlorides are reported, three of which have been structurally characterized. The synthesis of a new, structurally authenticated BIAN ligand is also described. We report the results of the use of these BIAN imidazolium salts as antimicrobials against the pathogens S. aureus, B. subtilis, E. coli and P. aeruginosa. The antimicrobial efficacies were particularly high for the N-(2,6-diisopropylphenyl)- and N-(mesityl)- substituted BIAN imidazolium salts (MIC values < 0.6 μg/mL).

Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos

N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10–12 h. One hundred percent mortality was observed at concentrations ≥50 µM. At sub-lethal concentrations (10–30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%–40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.

BIAN N-Heterocyclic Gold Carbene Complexes induced cytotoxicity in human cancer cells via upregulating oxidative stress.

BACKGROUND Nanoparticles of gold and silver are offering revolutionary changes in the field of cancer therapy. N-heterocyclic carbene (NHC) metal complexes possess diverse biological activities and are being investigated as potential chemotherapeutic agents. The purpose of this study was to examine the cytotoxicity and possible mechanisms of action of two types of newly synthesized nanofiber composites containing BIAN N-heterocyclic gold carbene complexes in two types of human cancer cells, namely breast cancer (MCF7) and liver cancer (HepG2) cells and also in normal human embryonic kidney cells (HEK 293). MATERIALS AND METHODS Cytotoxicity was assessed by MTT cell viability assay and oxidative stress by checking the total glutathione level. RESULTS Both compounds affected the cell survival of the tested cell lines at very low concentrations (IC50 values in the micro molar range) as compared to a well-known anti-cancer drug, 5 fluorouracil. A 60-80% depletion in total glutathione level was detected in treated cells. CONCLUSIONS Reduction in total glutathione level is one of the biochemical pathways for the induction of oxidative stress which in turn could be a possible mechanism of action by which these compounds induce cytotoxicity in cancer cell lines. The in vitro toxicity towards cancer cells found here means that these molecules could be potential anticancer candidates.