Axial ligand and spin-state influence on the formation and reactivity of hydroperoxo-iron(III) porphyrin complexes

The present study focuses on the formation and reactivity of hydroperoxo-iron(III) porphyrin complexes formed in the [Fe(III)(tpfpp)X]/H(2)O(2)/HOO(-) system (TPFPP=5,10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphyrin; X=Cl(-) or CF(3) SO(3)(-)) in acetonitrile under basic conditions at -15 °C. Depending on the selected reaction conditions and the active form of the catalyst, the formation of high-spin [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] could be observed with the application of a low-temperature rapid-scan UV/Vis spectroscopic technique. Axial ligation and the spin state of the iron(III) center control the mode of O-O bond cleavage in the corresponding hydroperoxo porphyrin species. A mechanistic changeover from homo- to heterolytic O-O bond cleavage is observed for high- [Fe(III)(tpfpp)(OOH)] and low-spin [Fe(III)(tpfpp)(OH)(OOH)] complexes, respectively. In contrast to other iron(III) hydroperoxo complexes with electron-rich porphyrin ligands, electron-deficient [Fe(III)(tpfpp)(OH)(OOH)] was stable under relatively mild conditions and could therefore be investigated directly in the oxygenation reactions of selected organic substrates. The very low reactivity of [Fe(III)(tpfpp)(OH)(OOH)] towards organic substrates implied that the ferric hydroperoxo intermediate must be a very sluggish oxidant compared with the iron(IV)-oxo porphyrin π-cation radical intermediate in the catalytic oxygenation reactions of cytochrome P450.     

An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite

Our recent studies identified a novel pathway of nicotinamide metabolism that involves 4-pyridone-3-carboxamide-1-β-D-ribonucleoside (4PYR) and demonstrated its endothelial cytotoxic effect. This study tested the effects of 4PYR and its metabolites in experimental models of breast cancer. Mice were divided into groups: 4T1 (injected with mammary 4T1 cancer cells), 4T1 + 4PYR (4PYR-treated 4T1 mice), and control, maintained for 2 or 21 days. Lung metastasis and endothelial function were analyzed together with blood nucleotides (including 4PYR), plasma amino acids, nicotinamide metabolites, and vascular ectoenzymes of nucleotide catabolism. 4PYR metabolism was also evaluated in cultured 4T1, MDA-MB-231, MCF-7, and T47D cells. An increase in blood 4PYR in 4T1 mice was observed at 2 days. 4PYR and its metabolites were noticed after 21 days in 4T1 only. Higher blood 4PYR was linked with more lung metastases in 4T1 + 4PYR vs. 4T1. Decreased L-arginine, higher asymmetric dimethyl-L-arginine, and higher vascular ecto-adenosine deaminase were observed in 4T1 + 4PYR vs. 4T1 and control. Vascular relaxation caused by flow-dependent endothelial activation in 4PYR-treated mice was significantly lower than in control. The permeability of 4PYR-treated endothelial cells was increased. Decreased nicotinamide but enhanced nicotinamide metabolites were noticed in 4T1 vs. control. Reduced N-methylnicotinamide and a further increase in Met2PY were observed in 4T1 + 4PYR vs. 4T1 and control. In cultured breast cancer cells, estrogen and progesterone receptor antagonists inhibited the production of 4PYR metabolites. 4PYR formation is accelerated in cancer and induces metabolic disturbances that may affect cancer progression and, especially, metastasis, probably through impaired endothelial homeostasis. 4PYR may be considered a new oncometabolite.Subject terms: Mechanisms of disease, Pathogenesis, Breast cancer     

1, 5- and 4, 6-Benzo[h]naphthyridines and stability constants of their complexes with nickel(II), cobalt(II), copper(II) and cadmium(II) determined by the potentiometric method

Summary Using the potentiometric method, the protonation constants of 1, 5- and 4, 6-benzo[h]naphthyridine (bn), as well as the stability constants of their complexes with nickel(II), cobalt(II), copper(II), or cadmium(II) were determined.     

Strongly countable dimensional compacta form the Hurewicz set

The hyperspaces of strongly countable dimensional compacta of positive dimension and of strongly countable dimensional continua of dimension greater than 1 in the Hilbert cube are homeomorphic to the Hurewicz set of all nonempty countable closed subsets of the unit interval [0,1]. These facts hold true, in particular, for covering dimension dim and cohomological dimension dimG, where G is any Abelian group.     

On existence of cone-maximal points in real topological linear spaces

A sufficient condition for a convex coneC in a Hausdorff topological linear space is given in order to ensure the existence of cone-maximal points. The condition becomes a necessary one in a topological linear space with a countable local base, that is, if the space is pseudometrizable. The paper extends known results to infinite dimensions and we answer Corley’s question in the affirmative with the exception of a pathological case.     

Regiospecific Hydrogenation of Bromochalcone by Unconventional Yeast Strains

This research aimed to select yeast strains capable of the biotransformation of selected 2′-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2′-hydroxy-2″-bromochalcone, 2′-hydroxy-3″-bromochalcone, 2′-hydroxy-4″-bromochalcone and 2′-hydroxy-5′-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2′-hydroxybromochalcones, the corresponding 2′-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances.     

Comparison of Calculated Values of the Lipophilicity of 2,6-Disubstituted 7-Methylpurines with Values Determined by RPTLC

JPC – Journal of Planar Chromatography – Modern TLC - The lipophilicity of 2,6-disubstituted 7-methylpurines and 6-mer-captopurine has been determined by reversed-phase thin-layer...     

The evidence for complex formation between N-acetyl-l-tyrosine methyl ester and N-acetylprocainamide hydrochloride using NMR spectroscopy

In order to reveal the possible mechanism of the recognition of antiarrhythmic agents class I and class III by the amino acid residues, which are responsible for drug binding to the selectivity filters either in the sodium or potassium ion channels, co-crystallizations of procainamide hydrochloride and N-acetylprocainamide hydrochloride with N-acetyl-l-tyrosine methyl ester and N-acetyl-l-phenylalanine methyl ester were performed using various conditions. Because the crystallization of the complexes failed, the intermolecular interactions between the components were evidenced using NMR spectroscopy. Exclusively, in the case of N-acetylprocainamide hydrochloride and N-acetyl-l-tyrosine methyl ester, two-dimensional NMR experiments and Job Plot analysis indicated the formation of the 1:1 complex in DMSO-d ₆  solution (with the association constant of 16 M⁻¹), whereas for the mixture of procainamide hydrochloride with N-acetyl-l-tyrosine methyl ester, the complex formation was not confirmed. The NMR results were discussed using crystal structure data obtained for N-acetylprocainamide hydrochloride, procainamide hydrochloride, as well as procainamide dihydrochloride, and were compared with the known pharmacological activity of the antiarrhythmic agents.     

A novel method for screening the glutathione transferase inhibitors

Background  

Glutathione transferases (GSTs) belong to the family of Phase II detoxification enzymes. GSTs catalyze the conjugation of glutathione to different endogenous and exogenous electrophilic compounds. Over-expression of GSTs was demonstrated in a number of different human cancer cells. It has been found that the resistance to many anticancer chemotherapeutics is directly correlated with the over-expression of GSTs. Therefore, it appears to be important to find new GST inhibitors to prevent the resistance of cells to anticancer drugs. In order to search for glutathione transferase (GST) inhibitors, a novel method was designed.