Solution structure, oxidative DNA damage, biological activity and molecular docking of ternary copper(II) L-argininato complexes.

Continuing our search for metal drugs with markedly higher toxicity to cancer cells than to normal cells, we evaluated the effect of 2,2'-bipyridine (bpy) as a co-ligand in the compounds [Cu(μ-O,O'-NO)(L-Arg)(bpy)]NO} (1) and [CuCl(L-Arg)(bpy)]Cl·3HO (2) (L-Arg = L-arginine), on DNA interaction, cytotoxic and antiproliferative activity, compared to the effects induced by other co-ligands i.e. 1,10-phenanthroline (phen) and SCN ions, in similar Cu(II) compounds we have studied previously.

Redox reactions of a pyrazine-bridged Ru(edta) binuclear complex: spectrochemical, spectroelectrochemical and theoretical studies.

The redox reactions of a pyrazine-bridged binuclear [(edta)RupzRu(edta)] (edta = ethylenediaminetetraacetate; pz = pyrazine) have been investigated spectrochemically and spectroelectrochemically for the first time. The kinetics of the reduction of [(edta)RupzRu(edta)] (Ru-Ru) with the ascorbic acid anion (HA) was studied as a function of ascorbic concentration and temperature at a fixed pH 6.0.

Insights into the binding of half-sandwich phosphino Ir(III) and Ru(II) complexes to deoxyribonucleic acid, albumin and apo-transferrin: Experimental and theoretical investigation.

A group of cytotoxic half-sandwich iridium(III) (Ir(η-Cp*)ClPPhCHOH (IrPOH)), (Ir(η-Cp*)ClP(p-OCHPh)CHOH (IrMPOH)), and ruthenium(II) (Ru(η-p-cymene)ClPPhCHOH (RuPOH), Ru(η-p-cymene)ClP(p-OCHPh)CHOH (RuMPOH)) complexes with phosphine ligands exhibit the ability to (i) slow hydrolysis which is reversed by adding a high NaCl concentration; (ii) oxidation of NADH to NAD; (iii) induction of cytotoxicity towards various cancer cell lines. Furthermore, we found that RuPOH and RuMPOH selectively inhibit the proliferation of skin cancer cells (WM266-4) while Ir(III) complexes were found to be moderate against prostate cancer cells (DU-145). Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, and molecular docking studies.

Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine-Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N-Methylphenethylamine.

The phosphine ligand (Ph PCH N(CH )(CH ) Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N-methylphenethylamine, was used to synthesize the half-sandwich iridium(III) (Ir(η -Cp*)Cl Ph PCH N(CH )(CH ) Ph, IrPNMPEA) and ruthenium(II) (Ru(η -p-cymene)Cl Ph PCH N(CH )(CH ) Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV-Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram-positive and Gram-negative bacterial strains was examined, indicating that both complexes are selective towards Gram-positive bacteria, e.

Liposomal Binuclear Ir(III)-Cu(II) Coordination Compounds with Phosphino-Fluoroquinolone Conjugates for Human Prostate Carcinoma Treatment.

Novel heteronuclear Ir-Cu coordination compounds ([Ir(η-Cp*)ClPcfx-Cu(phen)](NO)·1.75(CHOH)·0.75(HO) (), [Ir(η-Cp*)ClPnfx-Cu(phen)](NO)·1.

Copper(ii) complexes with 2-ethylpyridine and related hydroxyl pyridine derivatives: structural, spectroscopic, magnetic and anticancer studies.

Copper(ii) complexes with 2-ethylpyridine (1 and 2), 2-(hydroxyethyl)pyridine (3) and 2-(hydroxymethyl)pyridine (4) have been synthesized and characterized. All inorganic compounds have been studied by X-ray diffraction, thermogravimetry, vibrational and EPR spectroscopy as well as theoretical methods. The geometry of the complexes 1, 3 and 4 adopts nearly perfect geometry close to square planar (1, 4) or square pyramid (3) stereochemistry, respectively.

Therapeutic Potential of a Water-Soluble Silver-Diclofenac Coordination Polymer on 3D Pancreatic Cancer Spheroids.

This work describes the traditional wet and green synthetic approaches, structural features, and extensive bioactivity study for a new coordination polymer [Ag(-PTA)(Df)(HO)]·3HO () that bears a silver(I) center, a 1,3,5-triaza-phosphaadamantane (PTA) linker, and a nonsteroidal anti-inflammatory drug, diclofenac (Df). Compared to cisplatin, compound exhibits both anti-inflammatory properties and very remarkable cytotoxicity toward various cancer cell lines with a high value of selectivity index. Additionally, the 3D model representing human pancreas/duct carcinoma (PANC-1) and human lung adenocarcinoma (A549) was designed and applied as a clear proof of the remarkable therapeutic potential of .

Synthesis, physicochemical characterization and antiproliferative activity of phosphino Ru(II) and Ir(III) complexes.

Herein, we present the synthesis of new complexes based on ruthenium(II) (Ru(η--cymene)ClPPhCHOH (RuPOH) and Ru(η--cymene)ClP(-OCHPh)CHOH (RuMPOH)) and iridium(III) (Ir(η-Cp*)ClP(-OCHPh)CHOH (IrMPOH) and Ir(η-Cp*)ClPPhCHOH (IrPOH)) containing phosphine ligands with/without methoxy motifs on phenyl rings (P(-OCHPh)CHOH (MPOH) and PPhCHOH (POH)). The complexes were characterized by mass spectrometry, NMR spectroscopy (1D: H, C{H}, and P{H} and 2D: HMQC, HMBC, and COSY NMR) and elemental analysis. All the complexes were structurally identified by single-crystal X-ray diffraction analysis.

: Synthesis, Physicochemical, and Biological Properties of Phosphino Cu, Ru, Ir Complexes.

Two novel phosphine ligands, PhPCHN(CHCH) () and PhPCHN(CHCHCHCH) (), and six new metal (Cu(I), Ir(III) and Ru(II)) complexes with those ligands: iridium(III) complexes: Ir(η5-Cp*)Cl() (), Ir(η5-Cp*)Cl() () (Cp*: Pentamethylcyclopentadienyl); ruthenium(II) complexes: Ru(η6-p-cymene)Cl() (), Ru(η6-p-cymene)Cl() () and copper(I) complexes: [Cu(CHCN)()BF] (), [Cu(CHCN)()BF] () were synthesized and characterized using elemental analysis, NMR spectroscopy, and ESI-MS spectrometry. Copper(I) complexes turned out to be highly unstable in the presence of atmospheric oxygen in contrast to ruthenium(II) and iridium(III) complexes. The studied Ru(II) and Ir(III) complexes exhibited promising cytotoxicity towards cancer cells in vitro with IC values significantly lower than that of the reference drug-cisplatin.

Evaluation of anticancer activity in vitro of a stable copper(I) complex with phosphine-peptide conjugate.

[CuI(2,9-dimethyl-1,10-phenanthroline)P(p-OCH-Ph)CHSarcosineGlycine] (1-MPSG), highly stable in physiological media phosphino copper(I) complex-is proposed herein as a viable alternative to anticancer platinum-based drugs. It is noteworthy that, 1-MPSG significantly and selectively reduced cell viability in a 3D spheroidal model of human lung adenocarcinoma (A549), in comparison with non-cancerous HaCaT cells. Confocal microscopy and an ICP-MS analysis showed that 1-MPSG effectively accumulates inside A549 cells with colocalization in mitochondria and nuclei.

Isothiocyanate l-argininato copper(II) complexes - Solution structure, DNA interaction, anticancer and antimicrobial activity.

l-argininato copper(II) complexes have been intensively investigated in a variety of diseases due to their therapeutic potential. Here we report the results of comprehensive structural studies (ESI-MS, NIR-VIS-UV, EPR) on the complexes arising in aqueous solutions of two ternary copper(II) complexes with molecular formulas from crystal structures, [Cu(l-Arg)(NCS)](NCS)·HO (1) and [Cu(l-Arg)(NCS)] (2) (l-Arg = l-arginine). Reference systems, the ternary Cu(II)/l-Arg/NCS as well as binary Cu(II)/NCS and Cu(II)/l-Arg, were studied in parallel in aqueous solutions by pH-potentiometric titration, EPR and VIS spectroscopy to characterize stability, structures and speciation of the formed species over the broad pH range.

Interaction between DNA, Albumin and Apo-Transferrin and Iridium(III) Complexes with Phosphines Derived from Fluoroquinolones as a Potent Anticancer Drug.

A group of cytotoxic half-sandwich iridium(III) complexes with aminomethyl(diphenyl)phosphine derived from fluoroquinolone antibiotics exhibit the ability to (i) accumulate in the nucleus, (ii) induce apoptosis, (iii) activate caspase-3/7 activity, (iv) induce the changes in cell cycle leading to G2/M phase arrest, and (v) radicals generation. Herein, to elucidate the cytotoxic effects, we investigated the interaction of these complexes with DNA and serum proteins by gel electrophoresis, fluorescence spectroscopy, circular dichroism, and molecular docking studies. DNA binding experiments established that the complexes interact with DNA by moderate intercalation and predominance of minor groove binding without the capability to cause a double-strand cleavage.

Synthesis, structural characterization, docking simulation and in vitro antiproliferative activity of the new gold(III) complex with 2-pyridineethanol.

Gold(III) complex containing 2-pyridineethanol has been synthesized and characterized structurally by single crystal X-ray diffraction, vibrational spectroscopy, H NMR spectroscopy, electrochemical study, and DFT calculations. The Au(III) ion is four coordinated with one N-donor ligand (L) and three Cl anions. The Okuniewski's (τ'0.

Antibacterial activity and action mode of Cu(I) and Cu(II) complexes with phosphines derived from fluoroquinolone against clinical and multidrug-resistant bacterial strains.

Biological activity against reference and multi-drug resistant (MDR) clinical strains of fluoroquinolones (FQs): ciprofloxacin (HCp), norfloxacin (HNr), lomefloxacin (HLm) and sparfloxacin (HSf), phosphine ligands derived from those antibiotics and 14 phosphino copper(I) and copper(II) complexes with 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline or 2,2'-biquinoline have been determined. Almost all phosphines showed excellent antibacterial activity relative to reference strains (S. aureus ATCC 6538, E.

Protocol of proceedings with and optimization of ABTS method for detection of reactive oxygen species.

Characterization of the ability of DSM 15643 and DSM 20482 strains in the presence of Cu and HO to reactive oxygen species generation. Spectrophotometric ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) method was used. Determination of: MIC for Cu, HO and ABTS; survivability of under atmospheric oxygen exposure; the level and rate constants of free radicals production by the bacteria.

Copper(I) complexes with phosphines P(p-OCH-Ph)CHOH and P(p-OCH-Ph)CHSarGly. Synthesis, multimodal DNA interactions, and prooxidative and in vitro antiproliferative activity.

Phosphonium salt (p-OCH-Ph)P(CHOH)Cl (MPOHC), derived phosphine ligands without and with SarGly (Sarcosine-Glycine) peptide carrier P(p-OCH-Ph)CHOH (MPOH) and P(p-OCH-Ph)CHSarGly (MPSG), respectively, and two copper(I) complexes [Cu(I)(dmp)(MPOH)] (1-MPOH; dmp = (2,9-dimethyl-1,10-phenanthroline)) and [Cu(I)(dmp)(MPSG)] (1-MPSG) were synthesized. The resulting compounds were characterized by elemental analysis, 1D and 2D NMR and UV-Vis absorption spectroscopies, mass spectrometry, cyclic voltammetry and by X-ray diffraction analysis. Cytotoxicity of all compounds was evaluated in vitro against colon, lung, breast, pancreatic, prostate tumor cell lines, as well as towards non-tumor cell lines: lung, kidney and keratinocyte.

ROS-mediated lipid peroxidation as a result of Cu(ii) interaction with FomA protein fragments of F. nucleatum: relevance to colorectal carcinogenesis.

The ability of the studied FomA protein fragments of Fusobacterium nucleatum (Fn) with copper(ii) ions (Cu(ii)-Ac-KGHGNGEEGTPTVHNE-NH2 (1Cu) and its cyclic analogue Cu(ii)-cyclo(KGHGNGEEGTPTVHNE) (2Cu)) to induce reactive oxygen species (ROS) generation, as a result of red-ox processes, was determined by UV-Vis, luminescence methods, spin trapping and cyclic voltamperometry. The contribution of 1O2 and ˙OH to DNA degradation was proved using gel electrophoresis. Furthermore, the pronounced generation of ROS by mouse colon carcinoma cells (CT26) stimulated by both copper(ii) complexes was confirmed.

Cu(II) Complexes with FomA Protein Fragments of Increase Oxidative Stress and Malondialdehyde Level.

An explanation of carcinogenesis processes may certainly contribute to the prevention and development of novel methods for cancer treatment. In this paper, we considered the probable relationship between the presence of in the colon and its possible influence on the development of colorectal cancer. For this purpose, intracellular and/or extracellular generation of reactive oxygen species (ROS) by mouse colon carcinoma cells (CT26) was stimulated by two fragments of FomA adhesin from and their complexes with copper(II): Cu(II)-Ac-KGHGNG-NH () and Cu(II)-Ac-PTVHNE-NH ().

Selective Cu(I) complex with phosphine-peptide (SarGly) conjugate contra breast cancer: Synthesis, spectroscopic characterization and insight into cytotoxic action.

The main disadvantage of conventional anticancer chemotherapy is the inability to deliver the correct amount of drug directly to cancer. Those molecular delivering systems are very important to destroy cancer cells selectively. Herein we report synthesis of phosphine-peptide conjugate (PhPCH-Sar-Gly-OH, PSG) derived from SarGly (sarcosine-glycine), which can be easily exchanged to other peptide carriers, its oxide (OPhPCH-Sar-Gly-OH, OPSG) and the first copper(I) complex ([CuI(dmp)(P(Ph)CH-Sar-Gly-OH)], 1-PSG, where dmp stands for 2,9-dimethyl-1,10-phenanthroline).

Polymeric micelle-mediated delivery of half-sandwich ruthenium(II) complexes with phosphanes derived from fluoroloquinolones for lung adenocarcinoma treatment.

Novel half-sandwich ruthenium(II) complexes with aminomethyl(diphenyl)phosphine derived from fluoroloquinolones (RuPCp, RuPSf, RuPLm, RuPNr) were being investigated as alternatives to well-established metal-based chemotherapeutics. All compounds were characterized by elemental analysis, selected spectroscopic methods (i.e.

Relationship between copper(ii) complexes with FomA adhesin fragments of F. nucleatum and colorectal cancer. Coordination pattern and ability to promote ROS production.

The copper(ii) ion binding of the Ac-KGHGNG-NH2 and Ac-PTVHNE-NH2 fragments of FomA adhesin from Fusobacterium nucleatum was studied using potentiometry, UV-Vis, CD, EPR and DFT techniques. The coordination pattern was described in a wide range of pH values. Ligands begin interactions with metal ions using imidazole nitrogen.

Cu and Cu complexes with phosphine derivatives of fluoroquinolone antibiotics - A comparative study on the cytotoxic mode of action.

In this paper, we present a comparative study on the cytotoxic mode of action of copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic activity of four new compounds was tested against two selected cancer cell lines. All complexes exhibited much better cytotoxicity against both cell lines than unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp, SePNr) and previously described by us complexes with phosphines derived from different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as cisplatin.

Copper(i) complexes with phosphine derived from sparfloxacin. Part III: multifaceted cell death and preliminary study of liposomal formulation of selected copper(i) complexes.

The cytotoxic effect of iodide or thiocyanate copper(i) complexes (1-PSf, 2-PSf, 3-PSf, 4-PSf) with phosphine derived from sparfloxacin (HSf) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as diimine auxiliary ligands was proved in vitro on somatic (MRC-5) and neoplastic (MCF7) human cell lines. Differences in mode of action were investigated in-depth for the selected dmp and bq complexes (1-PSf, 3-PSf, respectively) by elucidation of the following: (i) the efficiency to produce reactive oxygen species (ROS) in biological systems (cyclic voltammetry); (ii) their impact on mitochondrial membrane potential; (iii) potency for the activation of caspases 3 and 9; (iv) influence on the degree of DNA degradation (comet assay). It was concluded that the apoptosis of cancer cells is directly connected to the caspase-dependent mitochondrial pathway and supported by ROS production along with irreversible DNA fragmentation.

Impact of the Cu(II) ions on the chemical and biological properties of goserelin - coordination pattern, DNA degradation, oxidative reactivity and in vitro cytotoxicity.

Goserelin acetate (Gos) as a synthetic analog of the mammalian gonadotropin-releasing hormone (GnRH) is widely used in the treatment of sex hormone-related conditions. In this paper we present the chemical and biological aspects of its interaction with Cu(II) ions. The mode of Cu(II) binding and the thermodynamic stability of the obtained complexes were characterized by potentiometry, UV-Vis and CD spectroscopic methods.