Interaction of methotrexate, an anticancer agent, with copper(II) ions : coordination pattern, DNA-cleaving properties and cytotoxic studies

The acid–base properties and the Cu(II) binding processes of methotrexate (MTX) were characterized by selected spectroscopic techniques and potentiometric measurements. The pH titration data showed that MTX behaves as a triprotic ligand. The deprotonation constants were determined for α-COOH and γ-COOH groups and (N1)H+ from the pteridine ring. Taking all the obtained results into consideration, a coordination pattern was proposed. The DNA-cleaving activity and reactive oxygen species (ROS) generation were investigated for both MTX and the Cu(II)–MTX system. The complex displayed a promising nuclease activity toward plasmid DNA in the presence of hydrogen peroxide. Interestingly, the induction of ROS, such as hydroxyl radicals, superoxide anions or singlet oxygen, was excluded and a different mechanism of DNA degradation was proposed. As MTX is now commonly used in anticancer therapy i.e. against lung cancer, basic cell-based studies were carried out to establish if its Cu(II) complex exhibits higher cytotoxic properties than the ligand alone. Activities of both compounds were also tested against colon carcinoma. Moreover, the determined values of IC50 were confronted with the cytotoxic activity of cisplatin

Copper(II) complexes with 2-ethylpyridine and related hydroxyl pyridine derivatives : structural, spectroscopic, magnetic and anticancer in vitro 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. The distortion of five coordinated copper(ii) ions in complex 2 indicates intermediate geometry between square pyramidal and trigonal pyramidal geometry. Further, the magnetic measurements have shown antiferromagnetic behaviour of the prepared complexes in a wide range of temperatures. The antiferromagnetic behaviour of 2 should originate from the superexchange interactions between each copper(ii) ion by the mixed chloride and μ(4)-O ion pathways. Besides, the weak antiferromagnetic character of 2 can be also attributed to the presence of intrachain exchange between dimeric units through double oxide ion. In complex 3, strong antiferromagnetic coupling between Cu(ii) centres in the Cu(2)O(2)Cl(2) moiety is found. The cytotoxicity of all compounds was tested in vitro against various cancer cell lines: human lung adenocarcinoma (A549), human breast adenocarcinoma (MCF7), human prostate carcinoma; derived from metastatic site: brain (DU-145) and two normal cell lines: human embryonic kidney (HEK293T) and human keratinocyte (HaCat). Furthermore, Pluronic P-123 micelles loaded with selected complexes (1 and 3) were proposed to overcome low solubility and to minimize systemic side effects. More detailed study revealed that complex 3 loaded inside micelles causes DU-145 cells' death with simultaneous decrease of mitochondrial membrane potential and a high level of reactive oxygen species generation. The stability of the compounds 1–4 in DMSO was confirmed by UV-Vis and FT-IR spectra studies

Liposomal binuclear Ir(III)–Cu(II) coordination compounds with phosphino-fluoroquinolone conjugates for human prostate carcinoma treatment

[Image: see text] Novel heteronuclear Ir(III)–Cu(II) coordination compounds ([Ir(η(5)-Cp*)Cl(2)Pcfx-Cu(phen)](NO(3))·1.75(CH(3)OH)·0.75(H(2)O) (1), [Ir(η(5)-Cp*)Cl(2)Pnfx-Cu(phen)](NO(3))·1.75(CH(3)OH)·0.75(H(2)O) (2), [Ir(η(5)-Cp*)Cl(2)Plfx-Cu(phen)](NO(3))·1.3(H(2)O)·1.95(CH(3)OH) (3), [Ir(η(5)-Cp*)Cl(2)Psfx-Cu(phen)] (4)) bearing phosphines derived from fluoroquinolones, namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx), and norfloxacin (Hnfx), have been synthesized and studied as possible anticancer chemotherapeutics. All compounds have been characterized by electrospray ionization mass spectrometry (ESI-MS), a number of spectroscopic methods (i.e., IR, fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry, variable-temperature magnetic susceptibility measurements, and X-ray diffractometry. The coordination geometry of Ir(III) in all complexes adopts a characteristic piano-stool geometry with the η(5)-coordinated and three additional sites occupied by two chloride and phosphine ligands, while Cu(II) ions in complexes 1 and 2 form a distorted square-pyramidal coordination geometry, and in complex 3, the coordination geometry around Cu(II) ions is a distorted octahedron. Interestingly, the crystal structure of [Ir(η(5)-Cp*)Cl(2)Plfx-Cu(phen)] features the one-dimensional (1D) metal–organic polymer. Liposomes loaded with redox-active and fluorescent [Ir(η(5)-Cp*)Cl(2)Pcfx-Cu(phen)] (1L) have been prepared to increase water solubility and minimize serious systemic side effects. It has been proven, by confocal microscopy and an inductively coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal form of compound 1 can be effectively accumulated inside human lung adenocarcinoma and human prostate carcinoma cells with selective localization in nuclei. A cytometric analysis showed dominance of apoptosis over the other cell death types. Furthermore, the investigated nanoformulations induced changes in the cell cycle, leading to S phase arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor spheroids has been demonstrated

The analysis of the parameters of the materials used for antiterrorist safety shields in marine vessels

Selected parameters of steel for constructional ballistic shields used in the Navy vessels have been presented. The standards for steel to be used for ballistic shields are established by safety standards institutions and committees. The analysis has been made upon currently available national and international steel types. The analysis made allowed to select the types of steel with the best parameters to be used for ballistic safety shields in marine vessels and give the direction for further research determined by contemporary threats of both military and terroristic nature. The paper presents inter alia: macroscopic images of a crater filled with the remains of grinded and eroded rifle missile with traces of adiabatic shear in the cut of steel disc, the diagram of a vessel of special purpose equipped with shields made of metal plates the Polish Register of Marine Vessels requirements for mechanical parameters of mild-alloy steel and welded joints of high resistance, the stress - strain diagram for steel 10GHMBA-E620T in speed of movement function, chemical constitution and resistance properties of representative steels used for ballistic shields on American and Japanese naval ships, chemical constitution of selected Swedish steels of high resistance applied for ballistic shields

Modeling and experimental verification of shooting bullets through the shield

Przedstawiono problematykę dotyczącą okrętowych osłon balistycznych zilustrowaną przykładami perforacji i penetracji. Podano zasadnicze modele znane z literatury penetracji i perforacji. Zaprezentowano teoretyczne krzywe penetracji dla dynamicznej wytrzymałości materiałów. Dokonano próby opisu wyników eksperymentalnych za pomocą znanych modeli.The issues concerning the ballistic protection shield are illustrated by the examples of penetration and perforation. The essential models known from the literature regarding the penetration and perforation are explained. The theoretical penetration characteristics for the dynamic endurance of materials are presented. There is an attempt to describe the experimental results by the means of the known models

Resistance to aging research in sea water composites with the polyester-glass recyclate

Composites are materials used for various types of constructions in the automotive industry, aviation, and shipbuilding. Due to the wide use of these materials, there is a problem with their recycling. Such material requires appropriate processing technology, which has been developed to obtain a recyclate with a specific granulation. The use of hand laminating technology made composites with the addition of polyester and glass recyclate with granulation of 1.2, as well as content: 0%, 20%, 30%. These types of materials are exposed to various types of atmospheric factors that affect their durability. Aging is defined as changes in the composite when exposed to atmospheric conditions, such as sunlight, temperature, thermal cycles, water in various forms and wind. This article uses recycled polyester and glass composites to investigate the effect of aging in seawater on their strength properties. These tests can be used to pre-assess the applicability of newly developed materials as construction or protective coatings. They were carried out on a specially prepared station for accelerated tests, with elevated temperature (35ºCC), as well as brine spray imitating sea atmosphere. The method is used to accelerate the aging processes occurring in composite materials. Samples were subjected to cycles of 5, 30 and 60 days respectively. Samples were weighed and measured before and after each cycle. In order to investigate the effect of aging on strength properties, the composites underwent a static tensile test in accordance with the standard for plastics. Studies have shown that as a result of the aging process, the strength properties decrease slightly, which affects the favourable assessment of these materials as constructional

The influence of granulation and content of polyester-glass waste on properties of composites

Glass fibre reinforced composites are used in many branches of industry. Polyester-glass laminates serve as structural material in shipbuilding (e.g. hulls of units, superstructures), in railways, automotive (e.g. elements of car bodies and interior fittings, roofs of wagons, cisterns) or aviation (e.g. aircraft fuselages, fuel tanks, completion beaks and ballasts). Factors affecting the increase of their use include low specific gravity, optimal strength properties, corrosion resistance. This is associated with a large amount of post-production and post-use waste. The recycling problem of these materials remains unresolved. The article presents the technology of processing polyester-glass waste in order to obtain a recycle with a specific granulation. The selected technology for the production of layered composites with reinforcement in the form of recycle is described. For testing, granulation was selected for 1.2 and 3 mm, as well as content: 0%, 10%, 20% and 30%. Using the water-cutting method, samples were prepared according to the standard static tensile test for plastics. The tests were carried out using a universal testing machine as well as an extensometer for samples with granulation of 1.2 mm and 3 mm, as well as the selected recycled percentage. Obtained results of the research indicated that granulation as well as content affects the strength properties of composites. As the granulation increases, at the same content, the material gains less deformation. The increase in the amount of the recycle reduces the strength properties of the material, and also due to the decrease in the deformation value - the material becomes brittle