Grażyna Stochel

Jagiellonian University, Cracovia, Lesser Poland Voivodeship, Poland

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Publications (66)230.8 Total impact

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    ABSTRACT: A set of homoleptic ruthenium polypyridine (bipyridine and terpyridine) complexes flanked with several electron-donating pyrrolidine moieties has been characterized and the anticancer activity was evaluated toward human lung adenocarcinoma epithelial (A549) and murine colon carcinoma (CT26). Good antiproliferative effects were observed with an IC50 ranging from ca. 4 to 21 μM against both cell lines. Dependence was found between the cytotoxicity, the lipophilicity and the RuII/RuIII oxidation potential. All the studied compounds interacted quite well with albumin while the interaction with DNA was marginal. The biological studies revealed that the ruthenium complexes induced the ROS overproduction which might be one but not the only way of cell death induction.
    No preview · Article · Dec 2015
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    ABSTRACT: The spectroscopic, photochemical, and biological studies of 5,10,15,20-tetrakis[2,6-difluoro-5(N-methylsulfamylo)phenyl]porphyrinate Zn(II) (ZnF2PMet) were carried out including absorption and fluorescence spectra, fluorescence quantum yields, triplet absorption spectra, triplet lifetimes, singlet oxygen quantum yield, and reactive oxygen species (ROS) detection under biological conditions and compared with its free-base analog (F2PMet). Zinc coordination into the porphyrin ring results in decrease of hydrophobicity and in higher cellular uptake. F2PMet localized specifically in endoplasmic reticulum and mitochondria while the ZnF2PMet is more diffused all over the cell, bonded to membrane proteins, as assessed by fluorescence microscopy. Zn-porphyrin exhibits greater singlet oxygen quantum yield than its free-base analog. Studies with fluorescent probes confirm that the ZnF2PMet produces mostly singlet oxygen, whereas F2PMet generates more hydroxyl radicals as the ROS. F2PMet is a more effective photosensitizer in vitro than its zinc complex, thus, the final photodynamic effect depends more on the nature of ROS than on the higher cellular uptake.
    No preview · Article · Sep 2015 · Journal of Coordination Chemistry

  • No preview · Article · Sep 2015 · RSC Advances

  • No preview · Article · Sep 2015
  • Justyna Polaczek · Łukasz Orzeł · Grażyna Stochel · Rudi van Eldik
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    ABSTRACT: The interaction with nitric oxide (NO) is an important aspect of the biological activity of vitamin B12 (Cbl). Whereas the formation of nitroxylcobalamin (CblNO) via the binding of NO to reduced CblCo(II) has been studied in detail before, the possible intracellular formation of CblNO via reduction of nitrocobalamin (CblNO2) is still questionable. To study this further, spectroscopic and kinetic studies on the reaction of CblNO2 with the intracellular antioxidant ascorbic acid (Asc) were performed in aqueous solution at the physiological pH of 7.2. It was found that the redox pathway of this reaction requires anaerobic conditions as a result of the rapid re-oxidation of reduced CblCo(II). In the studied system, both CblOH2 and CblNO2 are reduced to CblCo(II) by ascorbate at pH 7.2, the CblOH2 complex being two orders of magnitude more reactive than CblNO2. Clear evidence for redox cycling between CblOH2/CblNO2 and CblCo(II) under aerobic conditions was observed as an induction period during which all oxygen was used prior to the formation of CblCo(II) in the presence of an excess of ascorbate. No evidence for the intermediate formation of CblNO or NO radicals during the reduction of CblNO2 could be found. Graphical Abstract Nitrocob(III)alamin can be reduced by ascorbic acid under physiological conditions. The products of the reaction are cob(II)alamin and nitrite ion. This reaction is ca. 200 times slower than the one involving aquacob(III)alamin.
    No preview · Article · Aug 2015 · European Journal of Biochemistry
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    ABSTRACT: Six antibiotic-resistant Pseudomonas aeruginosa strains, isolated from chronic diabetic foot infections, were chosen for studying the influence of different chitosan-based materials: chitosan solution and chitosan submicroparticles in both planktonic and 24 h-old biofilm-forming models. Chitosan solution occurred to be more effective in the reduction of bacterial populations than chitosan submicroparticles for both planktonic and biofilm-related Pseudomonas cells. It seems that the antimicrobial activity of the tested chitosan preparations depends on the individual bacterial strain susceptibility probably related to differences in the phenotypes and natural antioxidant abilities of Pseudomonas aeruginosa strains. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
    No preview · Article · Apr 2015 · Journal of Biomaterials Applications
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    ABSTRACT: The nature of chlorophyll interactions with copper(ii) ions varies considerably in organic solvents, depending on the dominant coordinative form. Besides formation of the metallo tetrapyrrolic complex, Cu(ii) ions can cause oxidation of the pigment, reversible or irreversible, which can lead to the destruction of the macrocyclic structure. All these reaction types can be distinguished within a quite narrow range of reaction conditions. The ability to form new metallo derivatives in either metalation or transmetalation reactions is obviously limited by the concentration of the potential oxidant, but can be secured below this level via suitable composition of the reaction system. The decisive factor in the selection of a specific reaction pathway is the presence of a potential ligand that can affect the reactivity of Cu(ii) for example by shifting its redox potential. Spectroscopic and electrochemical studies were performed in order to determine the predominant species of Cu(ii) in methanol, nitromethane and acetonitrile in the presence of chloride and acetate ions, as well as to assign their appropriate oxidizing ability. This allowed us to estimate the boundary conditions for the electron transfer processes in chlorophyll-Cu(ii) systems. Chlorophyll and its free base can undergo both types of electron transfer processes, however, they reveal different susceptibilities that make this class of ligands quite versatile markers in tuning the reactivity of metal ions in solutions.
    Full-text · Article · Feb 2015 · Dalton Transactions
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    ABSTRACT: Understanding the redox cycling of metal ions in natural and biomimetic systems for dioxygen activation in catalytic oxidation processes at the molecular level has stood at the center of interest for many years, both from fundamental and applied perspectives. In this review, kinetic and mechanistic studies on peroxide activation by iron porphyrin models of heme enzymes, as well as by manganese complexes, are reported. Valuable information on the mechanistic details of dioxygen activation and oxygen atom transfer reactions by cytochrome P450 obtained from biomimetic studies with the application of model heme complexes is presented. Detailed mechanistic insight into particular steps of the catalytic cycle of enzyme model compounds was obtained through the application of ambient or low temperature rapid scan and high pressure techniques, supported by computational studies. Efforts undertaken to find reaction conditions and appropriate synthetic porphyrin models that allow the generation and significant stabilization of the mimics of intermediates responsible for oxygen transfer in the catalytic cycle of cytochrome P450 or peroxidases, which reflect reactivities comparable to that observed in native enzymes, are described. The review covers studies on peroxide activation not only by iron(III) porphyrin complexes for the oxidation of organic compounds, but also by simple manganese(II) and manganese(III/IV) complexes capable of conducting efficient organic dyes degradation. Throughout this report, redox cycling of the central metal ion plays an important role and controls the pathway of the oxidation processes.
    Full-text · Article · Feb 2015 · Coordination Chemistry Reviews
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    ABSTRACT: In this account, important mechanistic aspects concerning nitric oxide activation by selected iron and ruthenium complexes of biological and environmental relevance are surveyed. Throughout the sampling of kinetic and mechanistic investigations, particular emphasis is given to the elucidation of elementary reaction steps determining the dynamics of NO-metal interactions as well as to the evaluation of the electronic nature and stability/reactivity of metal activated forms of nitric oxide in the resulting nitrosyl products. The broad chemical diversity of the reviewed systems including metal, ligand, and solvent effects enabled to draw informative conclusions regarding the mechanistic picture of metal-assisted activation of nitric oxide, which are essential not only to improve the understanding of even more sophisticated NO processes developed by nature in biologic systems but also to design and tune novel enzyme mimics and catalysts for medical and environmental applications.
    Full-text · Article · Jan 2015 · Advances in Inorganic Chemistry

  • No preview · Chapter · Jan 2015
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    ABSTRACT: In this paper we report the reaction of [Ru(h5 -C5H5)Cl(PPh3)2] with P{CH2N(CH2CH2)2O}3 in the presence of NaBF4, in which, apart from the Cl� substitution, an unexpected P–C bond cleavage in the tertiary phosphane is observed. It results in the formation of [Ru(h5 -C5H5)(PH{CH2N(CH2CH2)2O}2)(PPh3)2]BF4 (1) – the first “pianostool” ruthenium complex with a secondary aminomethylphosphane ligand
    No preview · Article · Dec 2014 · RSC Advances
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    ABSTRACT: High pressure in combination with optical spectroscopy was used to gain insights into the interactions between Mg(2+), Zn(2+), and Ni(2+) ions and macrocyclic ligands of porphyrinoid type. In parallel, the central metal ion-macrocycle bonding was investigated using theoretical approaches. The symmetry properties of the orbitals participating in this bonding were analyzed, and pigment geometries and pressure/ligation effects were computed within DFT. Bacteriopheophytin a was applied as both a model chelator and a highly specific spectroscopic probe. The analysis of solvent and pressure effects on the spectral properties of the model Mg(2+), Zn(2+), and Ni(2+) complexes with bacteriopheophytin a shows that various chemical bonds are formed in the central pocket, depending on the valence configuration of the central metal ion. In addition, the character of this bonding depends on symmetry of the macrocyclic system. Since in most cases it is not coordinative bonding, these results challenge the conventional view of metal ion bonding in such complexes. In (labile) complexes with the main group metals, the metal ion-macrocycle interaction is mostly electrostatic. Significantly, water molecules are not preferred as a second axial ligand in such complexes, mainly due to the entropic constraints. The metal ions with a closed d shell may form (stable) complexes with the macrocycle via classical coordination bonds, engaging their p and s orbitals. Transition metals, due to the unfilled d shell, do form much more stable complexes, because of strong bonding via both coordination and covalent interactions. These conclusions are confirmed by DFT computations and theoretical considerations, which altogether provide the basis to propose a consistent and general mechanism of how the central metal ion and its interactions with the core nitrogens govern the physicochemical properties of metalloporphyrinoids.
    Full-text · Article · Jul 2014 · Inorganic Chemistry
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    ABSTRACT: Blood flow and pO2 changes after vascular-targeted PDT (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F2BMet) as photosensitizer, were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F2BMet generates both singlet oxygen and hydroxyl radicals under NIR irradiation, which consume oxygen. Partial oxygen pressure was lowered in PDT-treated tumors and this was ascribed both to oxygen consumption during PDT and to fluctuations in oxygen transport after PDT. Similarly, microcirculatory blood flow changes as a result of the disruption of blood vessels due to the treatment. A novel non-invasive approach combining Electron Paramagnetic Resonance oximetry and Laser Doppler blood perfusion measurements allowed longitudinal monitoring of hypoxia and vascular function changes in the same animals, after PDT. C-PDT induced parallel changes in tumor pO2 and blood flow, i.e., an initial decrease immediately after treatment, followed by a slow increase. In contrast, V-PDT led to a strong and persistent depletion of pO2, although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase of VEGF level 24h after treatment. C-PDT caused a ca. 5-day delay in tumor growth, while V-PDT was much more efficient and led to tumor growth inhibition in 90% of animals. The tumors of 44% of mice treated with V-PDT regressed completely and did not reappear for over one year. In conclusion, mild and transient hypoxia after C-PDT led to intense pO2 compensatory effects and modest tumor inhibition but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition.
    Full-text · Article · May 2014 · Advances in Free Radical Biology & Medicine
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    ABSTRACT: Progress in the photodynamic therapy (PDT) of cancer should benefit from a rationale to predict the most efficient of a series of photosensitizers that strongly absorb light in the phototherapeutic window (650-800 nm) and efficiently generate reactive oxygen species (ROS=singlet oxygen and oxygen-centered radicals). We show that the ratios between the triplet photosensitizer-O2 interaction rate constant (kD ) and the photosensitizer decomposition rate constant (kd ), kD /kd , determine the relative photodynamic activities of photosensitizers against various cancer cells. The same efficacy trend is observed in vivo with DBA/2 mice bearing S91 melanoma tumors. The PDT efficacy intimately depends on the dynamics of photosensitizer-oxygen interactions: charge transfer to molecular oxygen with generation of both singlet oxygen and superoxide ion (high kD ) must be tempered by photostability (low kd ). These properties depend on the oxidation potential of the photosensitizer and are suitably combined in a new fluorinated sulfonamide bacteriochlorin, motivated by the rationale.
    Full-text · Article · Apr 2014 · Chemistry - A European Journal
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    ABSTRACT: The previously published method allowing the separation of non-ferric (iron-free) and ferric (iron-saturated) forms of human serum transferrin via capillary electrophoresis has been further developed. Using a surface response methodology and a three-factorial Doehlert design we have established a new optimized running buffer composition: 50mM Tris-HCl, pH 8.5, 22.5% (v/v) methanol, 17.5mM SDS. As a result, two previously unobserved monoferric forms of protein have been separated and identified, moreover, the loss of ferric ions from transferrin during electrophoretic separation has been considerably reduced by methanol, and the method selectivity has been yet increased resulting in a total separation of proteins exerting only subtle or none difference in mass-to-charge ratio. The new method has allowed us to monitor the gradual iron saturation of transferrin by mixing the iron-free form of protein with the buffers with different concentrations of ferric ions. It revealed continuously changing contribution of monoferric forms, characterized by different affinities of two existing iron binding sites on N- and C-lobes of protein, respectively. Afterwards, the similar experiment has been conducted on-line, i.e. inside the capillary, comparing the effectiveness of two possible modes of the reactant zones mixing: diffusion mediated and electrophoretically mediated ones. Finally, the total time of separation has been decreased down to 4min, taking the advantage from a short-end injection strategy and maintaining excellent selectivity.
    No preview · Article · Mar 2014 · Journal of Chromatography A
  • Maria Oszajca · Ewa Kuliś · Grażyna Stochel · Małgorzata Brindell
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    ABSTRACT: The interference of NAMI-A ([ImH][RuCl4(Im)(DMSO)], Im – imidazole, DMSO – dimethyl sulfoxide) with the metabolism of nitric oxide (NO) has been proposed as one of the possible pathways of the antimetastatic activity of this complex. With regard to this observation we present herein detailed spectrophotometric studies on interaction of the NAMI-A complex with NO. The reactivity of NAMI-A toward NO has been studied in aqueous solution under physiological-like conditions (pH = 7.4, [NaCl] = 0.1 M, T = 37 °C). The ability of NAMI-A as well as its hydrolytic products to bind NO has been confirmed spectrophotometrically and separation of reaction products was performed with application of the HPLC technique. The relatively slow NO binding requires opening up a coordination site in the parent NAMI-A complex via simultaneously occurring hydrolysis. The studies in the presence of albumin showed that NO can coordinate to NAMI-A–albumin adducts. The capability of nitrosyl derivatives (Ru2+–NO+) to undergo reduction of the NO+ moiety in the presence of ascorbic acid, glutathione and dithionite has been studied with application of the NO sensor. The obtained results showed that under selected conditions, nitrosyl complexes cannot liberate nitric oxide via one electron reduction using applied reductants. This is due to the relatively low reduction potential of the NO+ group bound to Ru(II) (−0.69 V), determined in electrochemical studies.
    No preview · Article · Feb 2014 · New Journal of Chemistry
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    ABSTRACT: A novel long-lifetime highly luminescent ruthenium polypyridyl complex containing 2-nitroimidazole moiety [Ru(dip)2(bpy-2-nitroIm)]Cl2 (dip=4,7-diphenyl-1,10-phenanthroline, bpy-2-nitroIm=4-[3-(2-nitro-1H-imidazol-1-yl)propyl]-2,2'-bipyridine) has been designed cancer treatment and imaging. The luminescence properties of the synthesized compound strongly depend on the oxygen concentration. Under oxygen-free conditions quantum yield of luminescence and the average lifetime of emission were found to be 0.034 and 1.9μs, respectively, which is ca. three times higher in comparison to values obtained in air-equilibrated solution. The binding properties of the investigated ruthenium complex to human serum albumin have been studied and the apparent binding constant for the formation of the protein-ruthenium adduct was determined to be 1.1×10(5)M(-1). The quantum yield and the average lifetime of emission are greatly enhanced upon binding of ruthenium compound to the protein. The DNA binding studies revealed two distinguished binding modes which lead to a decrease in luminescence intensity of ruthenium complex up to 60% for [DNA]/[Ru]<2, and enhancement of emission for [DNA]/[Ru]>80. Preliminary biological studies confirmed fast and efficient accumulation of the ruthenium complex inside cells. Furthermore, the ruthenium complex was found to be relatively cytotoxic with LD50 of 12 and 13μM for A549 and CT26 cell lines, respectively, under normoxic conditions. The retention and cellular uptake of ruthenium complex is enhanced under hypoxic conditions and its LD50 decreases to 8μM for A549 cell line.
    No preview · Article · Feb 2014 · Journal of inorganic biochemistry
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    ABSTRACT: High-valent iron-oxo species have been invoked as reactive intermediates in catalytic cycles of heme and nonheme enzymes. The studies presented herein are devoted to the formation of compound II model complexes, with the application of a water soluble (TMPS)FeIII(OH) porphyrin ([meso-tetrakis(2,4,6-trimethyl-3-sulfonatophenyl)porphinato]iron(III) hydroxide) and hydrogen peroxide as oxidant, and their reactivity toward selected organic substrates. The kinetics of the reaction of H2O2 with (TMPS)FeIII(OH) was studied as a function of temperature and pressure. The negative values of the activation entropy and activation volume for the formation of (TMPS)FeIVO(OH) point to the overall associative nature of the process. A pH-dependence study on the formation of (TMPS)FeIVO(OH) revealed a very high reactivity of OOH− toward (TMPS)FeIII(OH) in comparison to H2O2. The influence of N-methylimidazole (N-MeIm) ligation on both the formation of iron(IV)-oxo species and their oxidising properties in the reactions with 4-methoxybenzyl alcohol or 4-methoxybenzaldehyde, was investigated in detail. Combined experimental and theoretical studies revealed that among the studied complexes, (TMPS)FeIII(H2O)(N-MeIm) is highly reactive toward H2O2 to form the iron(IV)-oxo species, (TMPS)FeIVO(N-MeIm). The latter species can also be formed in the reaction of (TMPS)FeIII(N-MeIm)2 with H2O2 or in the direct reaction of (TMPS)FeIVO(OH) with N-MeIm. Interestingly, the kinetic studies involving substrate oxidation by (TMPS)FeIVO(OH) and (TMPS)FeIVO(N-MeIm) do not display a pronounced effect of the N-MeIm axial ligand on the reactivity of the compound II mimic in comparison to the OH− substituted analogue. Similarly, DFT computations revealed that the presence of an axial ligand (OH− or N-MeIm) in the trans position to the oxo group in the iron(IV)-oxo species does not significantly affect the activation barriers calculated for CH dehydrogenation of the selected organic substrates.
    No preview · Article · Jan 2014 · Chemistry - A European Journal
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    ABSTRACT: The presented results cover a comparative mechanistic study on the reactivity of compound (Cpd) I and II mimics of a water-soluble iron(III) porphyrin, [meso-tetrakis(2,4,6-trimethyl-3-sulfonatophenyl)porphinato]iron(III), Fe(III)(TMPS). The acidity of the aqueous medium strongly controls the chemical nature and stability of the high-valent iron(IV) oxo species. Reactivity studies were performed at pH 5 and 10, where the Cpd I and II mimics are stabilized as the sole oxidizing species, respectively. The contributions of ΔH(⧧) and ΔS(⧧) to the free energy of activation (ΔG(⧧)) for the oxidation of 4-methoxybenzaldehyde (4-MB-ald), 4-methoxybenzyl alcohol (4-MB-alc), and 1-phenylethanol (1-PhEtOH) by the Cpd I and II mimics were determined. The relatively large contribution of the ΔH(⧧) term in comparison to the -TΔS(⧧) term to ΔG(⧧) for reactions involving the Cpd II mimic indicates that the oxidation of selected substrates by this oxidizing species is clearly an enthalpy-controlled process. In contrast, different results were found for reactions with application of the Cpd I mimic. Depending on the nature of the substrate, the reaction at room temperature can be entropy-controlled, as found for the oxidation of 4-MB-alc, or enthalpy-controlled, as found for 1-PhEtOH. Importantly, for the first time, activation volumes (ΔV(⧧)) for the oxidation of selected substrates by both reactive intermediates could be determined. Positive values of ΔV(⧧) were found for reactions with the Cpd II mimic and slightly negative ones for reactions with the Cpd II mimic. The results are discussed in the context of the oxidation mechanism conducted by the Cpd I and II mimics.
    No preview · Article · Jan 2014 · Inorganic Chemistry
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    ABSTRACT: Two cuprous complexes with 1-(2-pyridylazo)-2-naphthol (PAN) or 4-(2-pyridylazo)resorcinol (PAR) and triphenylphosphines, [Cu(PAN)(PPh3)2]BF4 (1) and [Cu(PAR)(PPh3)2]BF4 (2), are described in this work. The structures of both compounds were characterized by NMR and UV–Vis spectroscopies, mass spectrometry, IR-ATR measurements and DFT calculations. The single crystal diffraction of both complexes confirmed that the coordination polyhedrons around the copper centres are distorted tetrahedrons. Interestingly, the PAR and the PAN ligands are not planar in the synthesized complexes. The ligands coordinate to the central copper(I) ions by only two nitrogen atoms: one from pyridine and one from an azo group. The oxygen atoms from the hydroxyl groups do not form bonds with copper, but take part in strong intramolecular hydrogen bonds, which stabilize the conformations of the ligands. It is noteworthy that these bonds have different characters. In complex 2 we observed a typical O–H� � �N hydrogen bond, whereas in complex 1 proton transfer takes place, resulting in O� � �H–N bond formation. DFT data confirm the different characters of the H-bonds observed in the X-ray structures.
    No preview · Article · Nov 2013 · Polyhedron