Cover Picture: Complexation and Extraction of PAHs to the Aqueous Phase with a Dinuclear Pt II Diazapyrenium‐Based Metallacycle (Chem. Eur. J. 41/2010)

Subcellular duplex DNA and G‐quadruplex interaction profiling of a hexagonal PtII metallacycle

[Abstract] Metal‐driven self‐assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host–guest, and stimuli‐responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in‐cell tracking of a Pt2L2 metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4‐rich regions. SCC co‐localizes with epit…

Complexation and Extraction of PAHs to the Aqueous Phase with a Dinuclear Pt II Diazapyrenium‐Based Metallacycle

New palladium and platinum metallacycles have been synthesized by reaction between a 2,7-diazapyrenium-based ligand and Pd(II) and Pt(II) complexes. The inclusion complexes between the metallacycles and polycyclic aromatic hydrocarbons (PAHs) in CD(3)NO(2) and D(2)O were studied by NMR spectroscopy. The structures of the inclusion complexes of the Pt metallacycle as host with pyrene, phenanthrene, and triphenylene were confirmed by single crystal X-ray crystallography. The association constants between the Pt metallacycle and the selected PAHs were determined in CH(3)CN following the characteristic charge-transfer band displayed in their UV/Vis absorption spectrum. Although in aqueous solut…

Spontaneous Self-Assembly of a 1,8-Naphthyridine into Diverse Crystalline 1D Nanostructures: Implications on the Stimuli-Responsive Luminescent Behaviour

The previously reported organic solid-state fluorophore 7-(3,4-dimethoxyphenyl)-2-ethoxy-4-phenyl-1,8-naphthyridine-3-carbonitrile 1 was found to spontaneously self-organize into diverse 1D crystalline nanostructures by choosing appropriate liquid phase self-assembly conditions. Experimental results, as well as DFT quantum calculations (at the M06-2X/6-31+G(d) level), shed light on the aggregation mechanism. This was found in good agreement with molecules being primarily joined together through intermolecular alignment caused by electrostatic interactions, as well as minimization of the steric repulsions. This alignment provokes the preferential growth of the crystalline materials into 1D a…

[2]Catenanes and inclusion complexes derived from self-assembled rectangular PdII and PtII metallocycles

New inclusion complexes and [2]catenanes were self-assembled from a fluorescent diazapyrenium based ligand, a PdII or PtII complex, and cyclic or acyclic electron rich aromatic guests in aqueous and organic media. The molecular rectangles display a π-deficient cavity suitable to incorporate π-donor aromatic systems. The inclusion complexes between the metallocycles and phenylenic (2a,b) and naphthalenic (3a,b–5a,b) derivatives were studied by NMR, UV-vis and fluorescence spectroscopy. The crystal structure of (3b) ⊂ 1a·6PF(6) confirmed the insertion of the guest into the cavity of the metallocycle. Following the same self-assembly strategy, the use of polyethers 6,7 as π-donors resulted in …

Self-assembled Pt2L2 boxes strongly bind G-quadruplex DNA and influence gene expression in cancer cells

Supramolecular Pt(ii) quadrangular boxes bind native and G-quadruplex DNA motifs in a size-dependent fashion. Three Pt molecular squares of distinct size show biological activity against cancer cells and heavily influence the expression of genes known to form G-quadruplexes in their promoter regions. The smallest Pt-box displays less activity but more selectivity for a quadruplex formed in the c-Kit gene.

Polymorphism-Triggered Reversible Thermochromic Fluorescence of a simple 1,8-Naphthyridine

The fluorescent behavior in the solid state of a naphthyridine-based donor–acceptor heterocycle is presented. Synthesized as a crystalline blue-emissive solid (Pbca), the compound can easily be transformed in its P21/c polymorphic form by heating. The latter material shows blue to cyan emission switching triggered by a reversible thermally induced phase transformation. This fact, the reversible acidochromism, and the strong anisotropic fluorescence of the compound in the solid state, account for the potential of 1,8-naphthyridines as simple and highly tunable organic compounds in materials science.

Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis

Abstract The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and COX-2 endotoxin induction in mouse peritoneal macrophages has been studied. Three of these compounds inhibited nitrite and PGE2 accumulation in a concentration dependent-manner at μM range. None of these active compounds affected iNOS, COX-2, COX-1 or PLA2 activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil inflammatory responses (LTB4 biosynthesis and Superoxide or elastase release). Active compounds were assayed by oral administration in the mouse air pouch model, where they inhibited nitrite accumulation without affecting PGE 2 levels or leukocyte …

DNA Binding Studies and Cytotoxicity of a Dinuclear PtII Diazapyrenium- Based Metallo-supramolecular Rectangular Box

The interaction with native DNA of a 2,7-diazapyrenium-based ligand 1 and its Pt II rectangular metal- lacycle 2 is explored through circular and linear dichroism and fluorescence spectroscopies. The metal-free ligand 1 binds through intercalation, with a binding constant of approximately 5 � 10 5 m � 1 , whereas the metallacycle 2 binds and bends the DNA with a bind- ing constant of 7 � 10 6 m � 1 . PCR assays show that metallo-supramolecular box 2 interferes with DNA transactions in vitro whereas the intercalator 1 does not. The metallacycle is active against four human cancer cell lines, with IC50 values ranging between 3.1 and 19.2 mm and shows similar levels of efficacy, but a differen…

An anti-inflammatory ditriazine inhibiting leukocyte functions and expression of inducible nitric oxide synthase and cyclo-oxygenase-2.

A ditriazine derivative (4,10-dichloropyrido[5,6:4,5]thieno[3,2-d':3, 2-d]-1,2,3-ditriazine (DTD)) inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B(4) production, without any effect on 5-lipoxygenase activity. This compound reduced nitric oxide (NO) and prostaglandin E(2) production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. DTD significantly reduced mouse paw oedema induced by carrageenan and also markedly reduced NO and prostaglandin E(2) levels in exudates from 24-h zymosan-stimulated mouse air pouch.…

6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.

The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE2 generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition. © 2003 Elsevier Science Ltd. All rights reserved.