Metamizole is an analgesic and antipyretic, but can cause neutropenia and agranulocytosis. We investigated the toxicity of the metabolites N-methyl-4aminoantipyrine (MAA), 4-aminoantipyrine (AA), N-formyl-4-aminoantipyrine (FAA) and N-acetyl-4-aminoantipyrine (AAA) on neutrophil granulocytes and on HL60 cells (granulocyte precursor cell line). MAA, FAA, AA, and AAA (up to 100 µM) alone were not toxic for HL60 cells or granulocytes. In the presence of the myeloperoxidase substrate H 2 O 2 , MAA reduced cytotoxicity for HL60 cells at low (<50 µM), but increased cytotoxicity at 100 µM H 2 O 2. Neutrophil granulocytes were resistant to H 2 O 2 and MAA. Fe 2+ and Fe 3+ were not toxic to HL60 cells, irrespective of the presence of H 2 O 2 and MAA. Similarly, MAA did not increase the toxicity of lactoferrin, hemoglobin or methemoglobin for HL60 cells. Hemin (hemoglobin degradation product containing a porphyrin ring and Fe 3+) was toxic on HL60 cells and cytotoxicity was increased by MAA. EDTA, N-acetylcystein and glutathione prevented the toxicity of hemin and hemin/MAA. The absorption spectrum of hemin changed concentrationdependently after addition of MAA, suggesting an interaction between Fe 3+ and MAA. NMR revealed the formation of a stable MAA reaction product with a reaction pathway involving the formation of an electrophilic intermediate. In conclusion, MAA, the principle metabolite of metamizole, increased cytotoxicity of hemin by a reaction involving the formation of an electrophilic metabolite. Accordingly, cytotoxicity of MAA/hemin could be prevented by the iron chelator EDTA and by the electron donors NAC and glutathione. Situations with increased production of hemin may represent a risk factor for metamizole-associated granulocytopenia.

A new water-soluble photocatalyst for singlet oxygen generation is presented. Its absorption extends to the red part of the spectrum, showing activity up to irradiation at 660 nm. Its efficiency has been compared to that of a commercial analogue (Rose Bengal) for the oxidation of l-methionine. The quantitative and selective oxidation was promising enough to encapsulate the photocatalyst in polymersomes. The singlet oxygen generated in this way can diffuse and remain active for the oxidation of l-methionine outside the polymeric compartment. These results made us consider the use of these polymersomes for antimicrobial applications. E. coli colonies were subjected to oxidative stress using the photocatalyst–polymersome conjugates and nearly all the colonies were damaged upon extensive irradiation while under the same red LED light irradiation, liquid cultures in the absence of porphyrin or porphyrin-loaded polymersomes were unharmed.Graphical abstract Electronic supplementary materialThe online version of this article (10.1007/s00775-017-1514-8) contains supplementary material, which is available to authorized users.

The discrete coordination compound [Cu4Cl8(3)4(MeOH)2] is obtained from the reaction of a chloroform solution of 1-(3,2':6',3''-terpyridin-4'-yl)ferrocene (3) with a methanol solution of CuCl2; the single crystal structure of [{Cu4Cl8(3)4(MeOH)2}. 0.7CHCl3. 1.8MeOH] is described. Two {Cu2Cl4(3)2(MeOH)} units are connected by bridging chlorido ligands to generate a centrosymmetric tetranuclear molecule featuring face-to-face π-interactions between ferrocene units and between tpy domains. Intermolecular π-stacking of ferrocene and tpy units lead to quadruple-decker stacking motifs in the solid-state. The tetranuclear compound represents a pair of μ-Cl bridged Cu(II) dimers exhibiting a weak antiferromagnetic coupling via the bridging chlorido ligands. The redox behaviour of 3 has been investigated by cyclic voltammetry and spectroelectrochemistry; a ferrocenyl oxidation process is observed for [Cu4Cl8(3)4(MeOH)2].

The preparation and characterization of 7-(4- (

with subsequent damage to the cell components and consequent cell death. [1] PDT can be used to target tumor cells and is typically utilized in a combination therapy regime, together with other modalities such as radiotherapy, chemotherapy, and surgery. To optimize cell damage in the tumor and prevent significant collateral damage to healthy cells, the PS should be specifically localized in the pathogenic region. The lifetime and mean diffusion lengths of different ROS are very variable and localization will ensure that illumination generates ROS close to, at the surface of, or inside malignant tumor cells.Of particular interest for development of efficient PDT systems are porphyrins because the photochemical and photophysical properties may be tuned through modification of the central metal ion (if present) or through peripheral substituents. [2][3][4][5] However, despite the great potential of porphyrins as photosensitizers, these compounds possess crucial limitations in terms of biomedical application [6,7] such as a high dark toxicity, rather low activity under physiological conditions and typically poor water solubility. Efficient strategies to overcome these limitations and at the same time harness the beneficial properties of porphyrins are the (bio)-conjugation of the porphyrin to natural or synthetic polymers [8][9][10][11] or their incorporation in biocompatible nano carriers. Nanocarriers suitable for PDT materials include organic and inorganic nanoparticles, [12][13][14][15][16][17] liposomes, [18][19][20][21] and block copolymer-based vesicles or micelles. [22][23][24] Synthetic vesicles with sizes in the nanometer range, so-called polymersomes, are particularly appealing as carriers because they can be prepared with desired properties, [25] such as biocompatibility, possess an inner cavity where water-soluble photosensitizers can be encapsulated, [26] membranes allowing the entrapment of a hydrophobic photosensitizer and exhibit improved mechanical stability and robustness compared to liposomes. [27] There are a few examples of porphyrin-incorporating polymersomes, mostly concerning the non-covalent loading of the hydrophobic membrane with water insoluble porphyrins. [11,[28][29][30][31][32][33] The aim of those studies was to use the photophysical properties of the porphyrins to improve in vivo imaging. We have previously reported the synthesis and characterization of a water soluble tetra-N-alkylpyridinioporphyrin tetrabromide (TPyCP) (Scheme 1) which efficiently generates singlet oxygen both free Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano-assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20-tetrakis(1-(6-ethoxy-6-oxohexyl)-4-pyridin-1-io)-21H,23H-porphyrin tetrabromide porphyrin is inserted into polymersomes in order ...