Synthesis of resorcinarene-based cavitands by new and conventional synthetic methods

A szupramolekuláris rendszereket azt teszi értékessé többek között, hogy olyan előre programozott szelektivitással rendelkező tulajdonságokat rendelhetünk hozzájuk, amelyek rendkívül változatos felhasználási területeken alkalmazhatóak. Megfelelően megépítve a szupramolekuláris sajátságokat mutató molekulát, képes lesz több alternatív lehetőség közül szelektíven kiválasztani a számára legmegfelelőbb részecskét, molekulát, reakcióutat a tudatos szerkezeti tervezésből adódóan. Ez a szelektivitás az összetett és olykor meglehetősen bonyolult szupramolekuláris struktúrák megfelelő részeinek kommunikációjának eredményeként fogható fel. A részegységek közötti kommunikáció közös nyelvét a nemkovalens intramolekuláris kölcsönhatások jelentik. Jean-Marie Lehn megfogalmazása szerint a szupramolekuláris kémia a molekulák között tervszerűen kialakított intermolekuláris kölcsönhatások kémiája [1-3], illetve ezen nemkovalens kötőerőkkel összetartott molekuláris asszociátumok keletkezésével, tulajdonságainak és alkalmazási lehetőségeinek vizsgálatával foglalkozó tudományág. A másodrendű kölcsönhatások energiája (2 - 350 kJmol-1 ) hasonlóan az elsőrendű kölcsönhatások energiájához (100 - 1000 kJmol-1 ) tág határok között változhat, de értékét tekintve többnyire egy nagyságrenddel kisebb. Ezek az intermolekuláris kötések gyengék, ezért sok kell belőlük, és a molekula megfelelő helyén kell kialakítani őket, hogy a várt hatást kapjuk. A szupramolekuláris kémia abból a felismerésből fejlődött ki, hogy a molekulaegyüttesek új és olykor meglepő tulajdonságokra tesznek, tehetnek szert az őket felépítő molekulákhoz képest. Ha egy rendszer reverzibilissé válik - disszociálhat, újraegyesülhet -, esetleg olyan molekulaegyüttes jelenik meg, amely képes az alkalmazkodásra, a fejlődésre, az evolúcióra [4], akkor ez a jelenség változatos lehetőségeket kínál a tudomány és a hétköznapi élet számára. Gyakorlati alkalmazásai több tudományterületen jelenhetnek meg: nanoreaktorok - nanotechnológia, molekuláris szelektorok, gyógyszerszállító rendszerek, fehérje tervezés, királis termékeket eredményező szintézisek katalizátorai. A másik fontos és értékes jellemzője a kémia ezen területének, hogy a különböző tudományterületek (fizika, biológia, kémia, orvostudományok, anyagtudományok stb.) kutatásai a szupramolekuláris „világban” találkozhatnak, ezzel ösztönözve egymás kutatásait, elősegítve a világ komplexebb megértését. Valamint annak a modern tudományos szemléletmódnak is megfelel, amely már megköveteli a kooperációt a különböző tudományterületek között. - 5 - E terület elismerését jelzi, hogy a nagy szelektivitással rendelkező szerkezet-specifikus kölcsönhatások kialakítására képes molekulák kifejlesztéséért Charles J. Pedersennek, Donald J. Cramnek és Jean-Marie Lehnnek ítélték oda az 1987. évi kémiai Nobel-díjat. A 2016. évi kémiai Nobel-díjat Jean-Pierre Sauvage, Sir J. Fraser Stoddart és Bernard L. Feringa kapta molekuláris gépek fejlesztéséért, amely azt mutatja, hogy a kémia e területe most is nagy érdeklődésre tart számot

Cultivation and characterization of pterygium as an ex vivo study model for disease and therapy

PURPOSE: Development of ex vivo model to study pathogenesis, inflammation and treatment modalities for pterygium. METHODS: Pterygium obtained from surgery was cultivated (3 months). Gravitational attachment method using viscoelastic facilitated adherence of graft and outgrowing cells. Medium contained serum as the only growth supplement with no use of scaffolds. Surface profiling of the multi-layered cells for hematopoietic- and mesenchymal stem cell markers was performed. Examination of cells by immunohistochemistry using pluripotency, oxidative stress, stemness, migration and proliferation, epithelial and secretory markers was performed. The effect of anti-proliferative agent Mitomycin C upon secretion of pro-inflammatory cytokines IL-6 and IL-8 was assessed. RESULTS: Cells showed high expression of migration- (CXCR4), secretory- (MUC1, MUC4) and oxidative damage- (8-OHdG) markers, and low expression of hypoxia- (HIF-1alpha) and proliferation- (Ki-67) markers. Moderate and low expression of the pluripotency markers (Vimentin and DeltaNp63) was present, respectively, while the putative markers of stemness (Sox2, Oct4, ABCG-2) and epithelial cell markers- (CK19, CK8-18) were weak. The surface marker profile of the outgrowing cells revealed high expression of the hematopoietic marker CD47, mesenchymal markers CD90 and CD73, minor or less positivity for the hematopoietic marker CD34, mesenchymal marker CD105, progenitor marker CD117 and attachment protein markers while low levels of IL-6 and IL-8 secretion ex vivo, were inhibited upon Mitomycin C treatment. CONCLUSION: Ex vivo tissue engineered pterygium consists of a mixture of cells of different lineage origin, suitable for use as a disease model for studying pathogenesis ex vivo, while opening possibilities for new treatment and prevention modalities

Weak Interactions of the Isomers of Phototrexate and Two Cavitand Derivatives

The interactions of two conformers of newly synthesized photoswitchable azobenzene analogue of methotrexate, called Phototrexate, with two cavitand derivatives, have been investigated in dimethyl sulfoxide medium. Photoluminescence methods have been applied to determine the complex stabilities and the related enthalpy and entropy changes associated to the complex formation around room temperature. Results show opposite temperature dependence of complex stabilities. The structure of the upper rims of the host molecules and the reordered solvent structure were identified as the background of the opposite tendencies of temperature dependence at molecular level. These results can support the therapeutic application of the photoswitchable phototrexate, because the formation of inclusion complexes is a promising method to regulate the pharmacokinetics of drug molecules

Anodic Polymerization of Phenylphenols in Methyl Isobutyl Ketone and Mesityl Oxide: Incorporation of a Cavitand into the Layers Formed for Sensing Phenols in Organic Media

The electropolymerization of three phenylphenol isomers was studied in methyl isobutyl ketone and mesityl oxide, and the remarkable differences highlighted the importance of the carbon– carbon double bond in mesityl oxide. In the case of each substrate, a brownish deposit formed during the electrooxidation. The obvious difference between the polymers formed from the two solvents was recognized via voltammetric signal enhancement of 4-methoxyphenol and 4-chlorophenol, and it was only observed in the case of mesityl oxide. The experiments highlighted that incorporation of a cavitand with biphenyl groups on the upper rim of the polymers of phenylphenols improved the results to a small extent. The cavitand was, itself, electroactive without any fouling effect. As 2-phenylphenol is by far the cheapest of the three isomers, a cavitand was incorporated into its polymer, which was exploited to solve analytical problems while mesityl oxide was used as solvent. Useful quantifications were achieved in organic solvents; however, it failed under aqueous conditions due to the high hydrophobicity of the deposit. Application of differential pulse voltammetry for 4-methoxyphenol and 4-chlorophenol gave detection limits of 9.28 and 50.8 µM in acetonitrile, respectively. This procedure resulted in the immobilization of cavitand derivatives onto the electrode’s surface, and the layer formed offered selective sensing of phenols by electrochemical methods

Palladium-Mediated Catalysis Leads to Intramolecular Narcissistic Self-Sorting on a Cavitand Platform

Palladium-catalyzed aminocarbonylation reactions have been used to directly convert a tetraiodocavitand intermediate into the corresponding carboxamides and 2-ketocarboxamides. When complex mixtures of the amine reactants are employed in competition experiments, no ‘mixed’ products possessing structurally different amide fragments are detected either by 1H or 13C NMR. Only highly symmetrical cavitands are sorted out of a large number of potentially feasible products, which represents a rare example of intramolecular, narcissistic self-sorting. The reactivity order of the amine reactants and the changes in the Gibbs energies calculated using the semiempirical PM6 model suggest that this self-sorting process is kinetically controlled

Synthesis of Novel Ferrocene-Benzofuran Hybrids via Palladium- and Copper-Catalyzed Reactions

The combination of the ferrocene skeleton with pharmacophores often leads to molecules with interesting biological properties. Five ferrocene-benzofuran hybrids of different structures were synthesized by transition metal catalyzed reactions. The efficiency of both homogeneous and heterogeneous catalytic methods was tested. The products were characterized using 1H, 13C NMR and FTIR spectroscopy, HRMS and cyclic voltammetry. The structure of one of the new compounds was also proved with X-ray crystallography. The new hybrids showed moderate cytotoxicity on MCF-7 and MDA-MB-231 cell lines. It is remarkable that the less curable MDA-MB-231 cell line was more sensitive to treatment with three ferrocene derivatives

Ploidy-dependent changes in the epigenome of symbiotic cells correlate with specific patterns of gene expression

The formation of symbiotic nodule cells in Medicago truncatula is driven by successive endoreduplication cycles and transcriptional reprogramming in different temporal waves including the activation of more than 600 cysteine-rich NCR genes expressed only in nodules. We show here that the transcriptional waves correlate with growing ploidy levels and have investigated how the epigenome changes during endoreduplication cycles. Differential DNA methylation was found in only a small subset of symbiotic nodule-specific genes, including more than half of the NCR genes, whereas in most genes DNA methylation was unaffected by the ploidy levels and was independent of the genes' active or repressed state. On the other hand, expression of nodule-specific genes correlated with ploidy-dependent opening of the chromatin as well as, in a subset of tested genes, with reduced H3K27me3 levels combined with enhanced H3K9ac levels. Our results suggest that endoreduplication-dependent epigenetic changes contribute to transcriptional reprogramming in the differentiation of symbiotic cells

Solvent Switched Weak Interaction of a 4-Quinazolinone with a Cavitand Derivative

Interaction of 4-quinazolinone with tetrakis (3,5-dicarboxylatophenoxy)-cavitand derivative has been studied in methanol and dimethylformamide media using fluorescence spectroscopy and molecular modeling methods. Results show temperature dependent complex formation: either the entropy gain or the high enthalpy changes are responsible for the formation of stable complexes in two separated temperature regions. However, different thermodynamic parameters are associated to different conformations of the complexes: while the high entropy gain associated to the formation of deeply included guest in methanol, the high entropy gain is associated with the formation of weakly included guest in dimethylformamide solvent. This finding highlights the importance of dynamic properties of the species interacted in different solvents

High-yielding synthesis of deepened cavitands bearing picolyl moieties on the upper rim

Conventional high-yielding reactions (such as etherification, condensation reactions) and palladium catalysed aminocarbonylation served as highly efficient synthetic tools for the synthesis of novel cav itands bearing Schiff-base and carboxamide/2-ketocarboxamide functionalities, respectively. In this way, two families of deepened cavitands with related structures possessing 2-, 3- and 4-picolylamine moieties on the upper rim have been synthesised. Unexpectedly high chemoselectivities towards tetracarbox amides and tetrakis(2-ketocarboxamides) have been observed. The aminocarbonylation of tetraiodoca vitand as an iodoaromatic substrate proved to be highly selective in two aspects: (i) no substantial formation of either the mono-, di- or trifunctionalized products was observed and (ii) no ‘mixed’ products possessing both carboxamide and 2-ketocarboxamide fragments, due to selective simple and double carbon monoxide insertion, were detected