Kompozit nanofilmek előállítása a komponensek rétegenkénti önrendeződéses adszorpciójával = Preparation of composite nanofilms using layer-by-layer self-assembly

A kutatási munka ereményeit a következő megállapításokban foglalom össze: 1) kidolgoztuk a kompozit nanofilmek felépítésében a hordozó felülethez rögzítés optimális módszerét 2) a részecske-polielektrolit multiréteges nanofilmek felépítéséhez alacsony disszociációfokú polielektrolitra van szükség 3) a részecske-polielektrolit filmek rétegszámát a részecske szuszpenzió töménysége befolyásolja 4) felületmódosított Stöber szilika részecskék alkalmasak rendezett szerkezetű mono- és multirétegek felépítésére L-B technikával 5) a Stöber szilika L-B filmek rendezettségét csökkentik a felületaktív adalékanyagok 6) új Stöber szilika felületmódosítási eljárást dolgoztunk ki 7) multiréteges nanofilmek L-B technikával történő kialakításakor a rétegek síkjára merőleges irányban a rendezettség egyenletes 8) a globuláris protein - agyagásvány filmekben a multiréteg képződés kizárólag az elektrosztatikai vonzó lölcsönhatásokra épül 9) a globuláris protein-agyagásvány filmekben a rétegek közötti összetartó erő a két egymást követő agyagásvány réteg részecskéinek horizontális átlapolódásából származik 10) a globuláris proteinek adszorpciója az agyagásvány lamella-réteggel borított felületen nő a protein molekulatömegének csökkeésével és töltéssűrűségének növekedésével 11) a multiréteges globuláris protein-agyagásvány lamella szerkezetek felületi durvasága a beépülő protein méretével nő | The project results are summarized as follows: 1) the anchoring method of film bilding strategy was optimized 2) particle-polyelectrolyte films can be build using weakly dissociated, low-charge polyelectrolytes 3) the particle suspension concentration infulences the possible number of layers that can be built 4) ordered two-dimensional nanofilms can be built with surface modified Stöber silica particles by using the Langmuir-Blodgett method 5) surfactant additives will decrease the ordering quality in the 2-D Stöber films 6) a new method of surface modification of Stöber silica particles has been worked out, for L-B deposition 7) in L-B deposition technique, the ordering of layers is of high quality, orthogonally to the plane of the layers 8) the multilayer formation from globular proteins with lamellar clay particles is vased solely on the electrostatic attraction forces 9) in the globular protein-layered clay particle multilayered films the film coherence is due to horizontal overlapping of the particles in the subsequent layers 10) the adsorption of globular proteins on the clay particle layer is governed by the size and the charge density of the protein 11) the size of the globular proteins directs the surface roughness of protein lamellar clay particle film

Inhibition of DNA methyltransferase leads to increased genomic 5-hydroxymethylcytosine levels in hematopoietic cells.

5-Hydroxymethylcytosine (5hmC) is produced from 5-methylcytosine (5mC) by Ten-eleven translocation (TET) dioxygenases. The epigenetic modification 5hmC has crucial roles in both cellular development and differentiation. The 5hmC level is particularly high in the brain. While 5mC is generally associated with gene silencing/reduced expression, 5hmC is a more permissive epigenetic mark. To understand its physiological function, an easy and accurate quantification method is required. Here, we have developed a novel LC-MS/MS-based approach to quantify both genomic 5mC and 5hmC contents. The method is based on the liberation of nucleobases by formic acid. Applying this method, we characterized the levels of DNA methylation and hydroxymethylation in mouse brain and liver, primary hepatocytes, and various cell lines. Using this approach, we confirm that the treatment of different cell lines with the DNA methyltransferase inhibitor 5-aza-2\u27-deoxycytidine leads to a decrease in 5mC content. This decrease was accompanied by an increase in 5hmC levels in cell lines of hematopoietic origin. Finally, we showed that ascorbate elevates the levels of 5hmC and augments the effect of 5-aza-2\u27-deoxycytidine without significantly influencing 5mC levels

Impact of copper and iron binding properties on the anticancer activity of 8-hydroxyquinoline derived Mannich bases

The anticancer activity of 8-hydroxyquinolines relies on complex formation with redox active copper and iron ions. Here we employ UV-visible spectrophotometry and EPR spectroscopy to compare proton dissociation and complex formation processes of the reference compound 8-hydroxyquinoline (Q-1) and three related Mannich bases to reveal possible correlations with biological activity. The studied derivatives harbor a CH2-N moiety at position 7 linked to morpholine (Q-2), piperidine (Q-3), and chlorine and fluorobenzylamino (Q-4) substituents. Solid phase structures of Q-3, Q-4·HCl·H2O, [(Cu(HQ-2)2)2]·(CH3OH)2·Cl4·(H2O)2, [Cu(Q-3)2]·Cl2 and [Cu(HQ-4)2(CH3OH)]·ZnCl4·CH3OH were characterized by single-crystal X-ray diffraction analysis. In addition, the redox properties of the copper and iron complexes were studied by cyclic voltammetry, and the direct reaction with physiologically relevant reductants (glutathione and ascorbic acid) was monitored. In vitro cytotoxicity studies conducted with the human uterine sarcoma MES-SA/Dx5 cell line reveal the significant cytotoxicity of Q-2, Q-3, and Q-4 in the sub- to low micromolar range (IC50 values 0.2-3.3 μM). Correlation analysis of the anticancer activity and the metal binding properties of the compound series indicates that, at physiological pH, weaker copper(ii) and iron(iii) binding results in elevated toxicity (e.g.Q4: pCu = 13.0, pFe = 6.8, IC50 = 0.2 μM vs.Q1: pCu = 15.1, pFe = 13.0 IC50 = 2.5 μM). Although the studied 8-hydroxyquinolines preferentially bind copper(ii) over iron(iii), the cyclic voltammetry data revealed that the more cytotoxic ligands preferentially stabilize the lower oxidation state of the metal ions. A linear relationship between the pKa (OH) and IC50 values of the studied 8-hydroxyquinolines was found. In summary, we identify Q-4 as a potent and selective anticancer candidate with significant toxicity in drug resistant cells. © The Royal Society of Chemistry