The synthesis of new potential photosensitizers. 1. Mono-carboxylic acid derivatives of tetraphenylporphyrin

Abstract  

A series of mono-alkylcarboxylic acid derivatives of tetraphenylporphyrin have been prepared. All the porphyrins were completely characterized by use of mass, ¹H NMR, UV–visible, and fluorescence spectroscopy. Experimental log P were determined by use of reversed-phase thin-layer chromatography with use of log P _Rekker. These porphyrins are potential photosensitizers in photodynamic therapy.     

Highly stereoselective synthesis of N-substituted π-conjugated phthalimides

A new regio- and stereoselective synthesis of (E)-N-(2-arylvinyl)phthalimides as well as phthalimide-containing (E,E)-buta-1,3-dienes and (E)-but-1-en-3-ynes has been developed. The one-pot ruthenium-catalyzed silylative coupling/iododesilylation sequence provides (E)-N-(2-iodovinyl)phthalimide 1, which undergoes palladium-catalyzed Suzuki–Miyaura or Sonogashira cross-coupling to afford stereodefined highly π-conjugated phthalimides and functionalized dienimides containing phthalimide groups.     

Unexpected Course of the Reaction of 2‐Unsubstituted 1H‐Imidazole 3‐Oxides with Ethyl Acrylate

The attempted ethenylation at C(2) of 2‐unsubstituted 1H‐imidazole N‐oxides with ethyl acrylate (=prop‐2‐enoate) in the presence of Pd(OAc)₂ does not occur. In contrast to the other aromatic N‐oxides, the [2+3] cycloaddition of imidazole N‐oxides predominates, and 3‐hydroxyacrylates, isomeric with the cycloadducts, are key products for the subsequent reaction. The final products were identified as dehydrated 2+1 adducts of 1H‐imidazole N‐oxide and ethyl acrylate. The role of the catalyst is limited to the dehydration of the intermediate 3‐hydroxypropanoates to give 1H‐imidazol‐2‐yl‐substituted acrylates.     

Synthesis of Bis‐Heterocyclic 1H‐Imidazole 3‐Oxides from 3‐Oxido‐1H‐imidazole‐4‐carbohydrazides

The reaction of 1H‐imidazole‐4‐carbohydrazides 1 , which are conveniently accessible by treatment of the corresponding esters with NH₂NH₂?H₂O, with isothiocyanates in refluxing EtOH led to thiosemicarbazides (=hydrazinecarbothioamides) 4 in high yields (Scheme 2). Whereas 4 in boiling aqueous NaOH yielded 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones 5 , the reaction in concentrated H₂SO₄ at room temperature gave 1,3,4‐thiadiazol‐2‐amines 6 . Similarly, the reaction of 1 with butyl isocyanate led to semicarbazides 7 , which, under basic conditions, undergo cyclization to give 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones 8 (Scheme 3). Treatment of 1 with Ac₂O yielded the diacylhydrazine derivatives 9 exclusively, and the alternative isomerization of 1 to imidazol‐2‐ones was not observed (Scheme 4). It is important to note that, in all these transformations, the imidazole N‐oxide residue is retained. Furthermore, it was shown that imidazole N‐oxides bearing a 1,2,4‐triazole‐3‐thione or 1,3,4‐thiadiazol‐2‐amine moiety undergo the S‐transfer reaction to give bis‐heterocyclic 1H‐imidazole‐2‐thiones 11 by treatment with 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione (Scheme 5).     

Minimization of the number of periodic points for smooth self-maps of simply-connected manifolds with periodic sequence of Lefschetz numbers

Let f be a smooth self-map of m-dimensional, m ≥ 4, smooth closed connected and simply-connected manifold, r a fixed natural number. For the class of maps with periodic sequence of Lefschetz numbers of iterations the authors introduced in [Graff G., Kaczkowska A., Reducing the number of periodic points in smooth homotopy class of self-maps of simply-connected manifolds with periodic sequence of Lefschetz numbers, Ann. Polon. Math. (in press)] the topological invariant J[f] which is equal to the minimal number of periodic points with the periods less or equal to r in the smooth homotopy class of f. In this paper the invariant J[f] is computed for self-maps of 4-manifold M with dimH ₂(M; ?) ≤ 4 and estimated for other types of manifolds. We also use J[f] to compare minimization of the number of periodic points in smooth and in continuous categories.     

Common Limits of Fibonacci Circle Maps

We show that limits for the critical exponent tending to ∞ exist in both critical circle homeomorphism of golden mean rotation number and Fibonacci circle coverings. Moreover, they are the same. The limit map is not analytic at the critical point, which is flat, but has non-trivial complex dynamics.     

Einstein-Hopf drag,Doppler shift of thermal radiation and blackbody drag: Three perspectives on quantum friction

The thermal friction force acting on an atom moving relative to a thermal photon bath has recently been calculated on the basis of the fluctuation-dissipation theorem. The thermal fluctuations of the electromagnetic field give rise to a drag force on an atom provided one allows for dissipation of the field energy via spontaneous emission. The drag force exists if the atomic polarizability has a nonvanishing imaginary part. Here, we explore alternative derivations. The damping of the motion of a simple harmonic oscillator is described by radiative reaction theory (result of Einstein and Hopf), taking into account the known stochastic fluctuations of the electromagnetic field. Describing the excitations of the atom as an ensemble of damped harmonic oscillators, we identify the previously found expressions as generalizations of the Einstein-Hopf result. In addition, we present a simple explanation for blackbody friction in terms of a Doppler shift of the thermal radiation in the inertial frame of the moving atom: The atom absorbs blue-shifted photons from the front and radiates off energy in all directions, thereby losing energy. The original plus the two alternative derivations provide for additional confirmation of an intriguing quantum friction effect, and leave no doubt regarding its existence.     

Magnetic properties of ZnFe2O4 nanoparticles

Fine particles of ZnFe₂O₄ were synthesized by a wet chemical method in the (80 wt.% Fe₂O₃ + 20 wt.% ZnO) system. The morphological and structural properties of the mixed system were investigated by scanning electron microscopy, X-ray diffraction, inductively coupled plasma atomic emission, and X-ray photoelectron spectroscopy. The major phase was determined to be the ZnFe₂O₄ spinel with particle size of 11 nm. The magnetic properties of the material were investigated by ferromagnetic resonance (FMR) in the temperature range from liquid helium to room temperature. A very intense, asymmetric FMR signal from ZnFe₂O₄ nanoparticles was recorded, which has been analyzed in terms of two Callen-lineshape lines. Temperature dependence of the FMR parameters was obtained from fitting the experimental lines with two component lines. Analysis of the FMR spectra in terms of two separate components indicates the presence of strongly anisotropic magnetic interactions.     

The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line

Leflunomide, an anti-inflammatory agent, has been shown to be effective in multiple myeloma (MM) treatment; however, the mechanism of this phenomenon has not been fully elucidated. The aim of the study was to assess the role of mitochondria and dihydroorotate dehydrogenase (DHODH) inhibition in the cytotoxicity of leflunomide in relation to the MM cell line RPMI 8226. The cytotoxic effect of teriflunomide—an active metabolite of leflunomide—was determined using MTT assay, apoptosis detection, and cell cycle analysis. To evaluate DHODH-dependent toxicity, the cultures treated with teriflunomide were supplemented with uridine. Additionally, the level of cellular thiols as oxidative stress symptom was measured as well as mitochondrial membrane potential and protein tyrosine kinases (PTK) activity. The localization of the compound in cell compartments was examined using HPLC method. Teriflunomide cytotoxicity was not abolished in uridine presence. Observed apoptosis occurred in a mitochondria-independent manner, there was also no decrease in cellular thiols level. Teriflunomide arrested cell cycle in the G2/M phase which is not typical for DHODH deficiency. PTK activity was decreased only at the highest drug concentration. Interestingly, teriflunomide was not detected in the mitochondria. The aforementioned results indicate DHODH- and mitochondria-independent mechanism of leflunomide toxicity against RPMI 8226 cell line.