RESUMO
Sulphidation of nZVI (S-nZVI) has shown to significantly improve the arsenic removal capacity of nZVI, concurrently modifying the sequestration mechanism. However, to better apply S-nZVI for groundwater arsenic remediation, the impact of groundwater coexisting ions on the efficacy of arsenic uptake by S-nZVI needs to be investigated. This present study evaluates the potential of S-nZVI to remove arsenic in the presence of typical groundwater coexisting ions such as Cl-, HA, HCO3-, PO43- and SO42- through batch adsorption experiments. Individually, PO43- and HA had a dominant inhibition effect, while SO42- promoted As(III) removal by S-nZVI. Conversely, for As(V) removal, HCO3- and SO42- impeded the removal process. X-ray spectroscopic investigation suggests that the coexisting ions can either compete with arsenic for the adsorption sites, influence the S-nZVI corrosion rates and/or generate distinct corrosion products, thereby interfering with arsenic removal by S-nZVI. To investigate the cumulative effects of these ions, a 25-1 Fractional Factorial Design of experiments was employed, wherein the concentration of all the ions were varied simultaneously in an optimized manner, and their impact on arsenic removal by S-nZVI was observed. Our results shows that when these ions are present concurrently, PO43-, SO42- and HA still exerted a dominant influence on As(III) removal, whereas HCO3- was the main ions affecting As(V) removal, although the combined influence of the ions was not merely a summation of their individual effects. Overall, the finding of our study might provide valuable insight for predicting the actual performance of S-nZVI in field-scale applications for the remediation of arsenic-contaminated groundwater.
RESUMO
In the present paper, we synthesized and characterized four N-donor polypyridyl copper(II) complexes (C1-C4); [Cu(mono-CN-PIP)2]2+ (C1), [Cu(tri-OMe-PIP)2]2+ (C2), [Cu(di-CF3-PIP)2]2+ (C3) and [Cu(DPPZ)2]2+ (C4). The (Calf-Thymus) CT-DNA binding studies depicted that the complexes could interact with DNA via intercalative mode. All the complexes, particularly C3 and C4 attenuated the proliferation as well as migration of various cancer cells, indicating their anti-cancer and anti-metastatic activity. Additionally, chick embryo angiogenesis (CEA) assay exhibited the inhibition of vascular sprouting in presence of C3 and C4, suggesting their potential in inhibiting the blood vessel growth. Mechanistic studies revealed that the complexes induced the excessive production of cellular reactive oxygen species (ROS) leading to apoptosis through up regulation of p53 and downregulation of Bcl-xL, which might be the plausible mechanisms underlying their anti-cancer properties. To understand the feasibility of practical application of anti-cancer copper complexes C3 and C4, in vivo sub-chronic toxicity study (4â¯weeks) was performed in C57BL6 mice and the results exhibited almost non-toxic effects induced by these complexes in terms of haematology and serum biochemical analyses, suggesting their biocompatible nature. The current study provides the basis for future advancement of other novel biocompatible metal complexes that could be employed for the therapy of different cancers.
Assuntos
Complexos de Coordenação , Cobre , Substâncias Intercalantes , Melanoma Experimental , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Embrião de Galinha , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Cobre/farmacologia , Humanos , Substâncias Intercalantes/síntese química , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Proteína Supressora de Tumor p53/metabolismo , Proteína bcl-X/metabolismoRESUMO
Copper is a part of various enzymes and helps them to function properly. It can be effectively used to produce promising anticancer drugs and presently, many studies are being pursued worldwide on the development of copper-based complexes as potential anticancer drugs. Herein, we briefly discuss the importance of reactive oxygen species in biological applications and copper(II) complexes as anticancer drugs. The anti-angiogenic properties of mono-nuclear copper(II) complexes have been demonstrated by in vivo chick embryo angiogenesis analysis. The plausible mechanism behind anticancer activity of these complexes is by the formation of excessive intracellular Reactive Oxygen Species (ROS). ROS is a composite term used for oxygen derivative non-radicals and free radicals of highly reactive components, that enhances the killing response of immune cells to microbial invasion. Previous reports have shown that ROS plays an important role as a messenger in cell cycling and normal cell signal transduction. Graphical Abstract The generation of singlet oxygen and healing the tumor cells with singlet oxygen in presence of UV-light.
Assuntos
Indutores da Angiogênese/química , Indutores da Angiogênese/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Cobre/química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The DNA binding studies of rutheniumu(II) polypyridyl complexes {[Ru(phen)2Mipc]2+, [Ru(bpy)2Mipc]2+, [Ru(dmb)2Mipc]2+, [Ru(phen)2BrIPC]2+, [Ru(bpy)2BrIPC]2+, [Ru(dmb)2BrIPC]2+, [Ru(phen)2PIP-Cl]2+, [Ru(bpy)2PIP-Cl]2+, [Ru(dmb)2PIP-Cl]2+, [Ru(phen)2IPPBA]2+, [Ru(bpy)2IPPBA]2+, [Ru(dmb)2IPPBA]2+} with DNA investigated by electronic absorption titration, emission and molecular modelling studies to identify the binding interactions. All these complexes are showing good binding constant values ~104 to 105. The intercalative ligands makes the binding of the ruthenium(II) complex with DNA as intercalation mode. The ancillary ligands 1,10-phenanthroline (phen), 4,4'-Dimethyl-2,2'-dipyridyl (dmb) and 2,2'-dipyridine (bpy) having been discovered found to be involved in bond formation with the phosphate backbone of nucleotide base pairs in ruthenium(II) complex-DNA docked complex. The molecular docking results are good agreement with experimental results. The molecular modelling technic should help to extend knowledge about the nature (or) mode of binding of these ruthenium(II) complexes with (calf thymus) CT-DNA.
Assuntos
DNA/metabolismo , Compostos Organometálicos/metabolismo , Rutênio/metabolismo , Espectroscopia por Absorção de Raios X/métodos , Sítios de Ligação , DNA/química , Modelos Moleculares , Compostos Organometálicos/química , Rutênio/químicaRESUMO
This article describes the synthesis and characterization of three new Ru(II) polypyridyl complexes including [Ru(phen)2(dpphz)]2+ (1), [Ru(bpy)2(dpphz)]2+ (2) and [Ru(dmb)2(dpphz)]2+ (3) where dpphz = dipyrido[3,2-a:2',3'-c] phenazine-11-hydrazide, phen =1,10-phenanthroline, bpy = 2,2'-bipyridine and dmb = 4,4'-dimethyl2,2'-bipyridine. The binding behaviors of these complexes to calf thymus DNA (CT-DNA) were explored by spectroscopic titrations, viscosity measurements. Results suggest that these complexes can bind to CT-DNA through intercalation. However, their binding strength differs from each other; this may be attributed to difference in the ancillary ligand. The cytotoxicity of 1-3 was evaluated by MTT assay; results indicated that all complexes have significant dose dependent cytotoxicity with HeLa tumor cell line. All complexes exhibited efficient photocleavage of pBR322 DNA upon irradiation. The DNA binding ability of 1-3 was also studied by docking the complexes into B-DNA using docking program.
Assuntos
Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Citotoxinas/farmacologia , Clivagem do DNA/efeitos dos fármacos , DNA/metabolismo , Compostos Organometálicos/farmacologia , Rutênio/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Bactérias/efeitos dos fármacos , Sítios de Ligação , Bovinos , Ciclo Celular/efeitos dos fármacos , Complexos de Coordenação/química , Citotoxinas/química , Clivagem do DNA/efeitos da radiação , Células HeLa , Humanos , Substâncias Intercalantes/química , Substâncias Intercalantes/farmacologia , Ligantes , Testes de Sensibilidade Microbiana , Compostos Organometálicos/químicaRESUMO
A series of four new mononuclear copper(II) polypyridyl complexes (1-4) have been designed, developed, and thoroughly characterized by several physicochemical techniques. The CT-DNA binding properties of 1-4 have been investigated by absorption, emission spectroscopy, and viscosity measurements. All the complexes especially 1 and 4 exhibit cytotoxicity toward several cancer cell lines, suggesting their anticancer properties as observed by several in vitro assays. Additionally, the complexes show inhibition of endothelial cell (HUVECs) proliferation, indicating their antiangiogenic nature. In vivo chick embryo angiogenesis assay again confirms the antiangiogenic properties of 1 and 4. The formation of excessive intracellular ROS (H2O2 and O2(â¢-)) and upregulation of BAX induced by copper(II) complexes may be the plausible mechanisms behind their anticancer activities. The present study may offer a basis for the development of new transition metal complexes through suitable choice of ligands for cancer therapeutics by controlling tumor angiogenesis.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/química , Neoplasias/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Piridinas/química , Inibidores da Angiogênese/síntese química , Animais , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Complexos de Coordenação/síntese química , DNA/metabolismo , Clivagem do DNA/efeitos dos fármacos , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Neoplasias/patologia , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
Three new compounds, [Ru(Hdpa)2PyIP](ClO4)2·2H2O (1) [Ru(Hdpa)2FyIP](ClO4)2·2H2O (2) and [Ru(Hdpa)2IIP](ClO4)2·2H2O (3) have been synthesized and characterized by spectroscopic techniques such as elemental analysis, UV/Vis, FT-IR, (1)H NMR, (13)C NMR and mass spectra. The CT-DNA binding properties of 1-3 have been investigated by absorption, emission spectroscopy and viscosity measurements. Experimental results suggested that they can interact with DNA through intercalative mode with different binding strengths. These were found to promote the cleavage of plasmid DNA. Cell viability results indicated that all compounds showed significant dose dependent cytotoxicity in selected cell lines and 1 shown higher cytotoxicity than cisplatin on HeLa cells. Cellular uptake studies were studied by flow cytometry and confocal microscopy.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , DNA/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Rubídio/química , Antineoplásicos/síntese química , Antineoplásicos/química , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-AtividadeRESUMO
The new ligand 4-(isopropylbenzaldehyde)imidazo[4,5-f ][1,10]phenanthroline (ippip) and its complexes [Ru(phen)(2)(ippip)](2+)(1),[Co(phen)(2)(ippip)](3+)(2),[Ru(bpy)(2)(ippip)](2+)(3),[Co(bpy)(2)(ippip)](3+)(4)(bpy=2,2-bipyridine) and (phen=1,10-phenanthroline) were synthesized and characterized by ES(+)-MS, (1)H and (13)C NMR. The DNA binding properties of the four complexes were investigated by different spectrophotometric methods and viscosity measurements. The results suggest that complexes bind to calf thymus DNA (CT-DNA) through intercalation. When irradiated at 365 nm, the complexes promote the photocleavage of pBR322 DNA, and complex 1 cleaves DNA more effectively than 2, 3, 4 complexes under comparable experimental conditions. Furthermore, photocleavage studies reveal that singlet oxygen ((1)O(2)) plays a significant role in the photocleavage.
Assuntos
Cobalto/química , DNA/metabolismo , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Piridinas/química , Rutênio/química , Absorção , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bovinos , Linhagem Celular Tumoral , DNA/química , Humanos , Desnaturação de Ácido Nucleico , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Processos Fotoquímicos , Espectrometria de Fluorescência , Estereoisomerismo , Especificidade por Substrato , Temperatura , ViscosidadeRESUMO
Two novel cobalt(III) pyridine complexes (1)[Co(en)2(py)2]3+ and (2)[Co(en)2(mepy)2]3+ (en=ethylenediamine, py=pyridine, and mepy=methylpyridine) have been synthesized and characterized. The interaction of these complexes with calf thymus DNA was investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photocleavage. Results suggest that the two complexes bind to DNA via groove mode and complex 2 binds more strongly to CT DNA than complex 1. Moreover, these Co(III) complexes have been found to promote the photocleavage of plasmid DNA pBR322 under irradiation at 365 nm, cytotoxicity results of complexes are also showing anticancer activity.
RESUMO
In this paper, three complexes of type [Co(en)(2)PIP](3+)(PIP=2-phenylimidazo[4,5-f][1,10,] phenanthroline)(1), [Co(en)(2)IP](3+) (IP = imidazo[4,5-f][1,10,] phenanthroline)(2), and [Co(en)(2)phen-dione](3+)(1,10 phenanthroline 5,6,dione)(3) have been synthesized and characterized by UV/VIS, IR, (1)H NMR spectral methods. Absorption spectroscopy, emission spectroscopy, viscosity measurements, and DNA melting techniques have been used for investigating the binding of these two complexes with calf thymus DNA, and photocleavage studies were used for investigating these binding of these complexes with plasmid DNA. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (= calf thymus DNA) by intercalation mode via IP or PIP into the base pairs of DNA, and complex 3 is binding as groove mode. Complex 1 binds more avidly to CT DNA than 2 and 3 which is consistent with the extended planar ring pi system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.