pH‐Responsive Hybrid Organic–Inorganic Ruthenium Nanoparticles for Controlled Release of Doxorubicin

The current study aims at preparing biocompatible hybrid organic–inorganic ruthenium core–shell nanostructures (RuNPs) coated with polyvinylpyrrolidone (PVP) and polyoxyethylene stearate (POES). Thereafter, the core/shell RuNPs are loaded with doxorubicin (to form RuPDox) with a loading efficiency > 60%. RuPDox possesses exceptional stability and pH‐responsive release kinetics with approx. 50% release of doxorubicin at up to 1 h exposure to an acidic endosomal environment. The cytotoxic effects of RuPDox are tested in vitro against breast cancer (MDA‐MB‐231), ovarian cancer (A2780), and neuroblastoma (UKF‐NB‐4) cells. Notably, although RuNPs have slight cytotoxicity only, RuPDox causes a synergistic enhancement of cytotoxicity when compared to free doxorubicin. Significant increase in free radicals formation, enhanced activity of executioner caspases 3/7, and higher expression of p53 and metallothionein is further identified due to the RuPDox treatment. Single‐cell gel electrophoresis reveals no additional contribution of RuNPs to genotoxicity of doxorubicin. Moreover, RuPDox promotes significantly increased stability of doxorubicin in human plasma and pronounced hemocompatibility assayed on human red blood cells. The results imply a high potential of biocompatible hybrid RuNPs with PVP‐POES shell as versatile nanoplatforms to enhance the efficiency of cancer treatment.     

Nucleolar asynchrony observed in HL-60 leukemic granulocytic precursors resistant to 5-aminolaevulinic acid-based photodynamic treatment

To provide more information on the 5-aminolaevulinic acid (ALA)-induced photodynamic effect on nucleoli, morphologically expressed nucleolar asynchrony (the presence of 'active' large nucleoli with an uniform distribution of RNA and 'resting' ring-shaped nucleoli in one and the same nucleus) was studied in cultured HL-60 leukemic granulocytic precursors using a simple cytochemical procedure for the demonstration of RNA. Nucleolar asynchrony was mainly expressed in cells which were apparently resistant to ALA-based photodynamic treatment (PDT) since most of them (about 75%) exhibited this phenomenon.     

Study of the time dependence of the stability of 5-aza-2′-deoxycytidine in acid medium

The stability of a solution of AzDC in acid medium (0.1 N HCl) was studied using thinlayer chromatography on cellulose. The R_f values of AzDC and its decomposition products are given in Table 1. The time course of the hydrolytic decomposition of AzDC in acid medium was studied on the basis of the decrease in the amount of AzDC. The amount of AzDC was quantitatively evaluated densitometrically at certain time intervals after chromatographic separation (Figs. 1, 2). After 10 hr the content of AzDC decreased from 100% at the beginning of the experiment to 23%; $\text{t}\text{2}$ (decomposition half-time) was found to be between 3.5 and 3.7 hr (Table 2, Fig. 3).     

On the domain dependence of solutions to the two-phase Stefan problem

We prove that solutions to the two-phase Stefan problem defined on a sequence of spatial domains _n ^N converge to a solution of the same problem on a domain where is the limit of _n in the sense of Mosco. The corresponding free boundaries converge in the sense of Lebesgue measure on ^N.     

Glass production in the Middle Ages from Italy to Central Europe: the contribution of archaeometry to the history of technology

The present paper reports and discusses data obtained by a combined archaeological and archaeometric study carried out on an assemblage of selected Medieval glass finds from the Monastery of St. Severus in Classe (Ravenna, Italy) and ascribable to the 13–16th CE. Glassware belonging to three main typological groups was selected for this study: ampoules, nuppenbecher and kropfflasche. Such a choice mainly stems from the intent to evaluate typological and compositional affinities of these peculiar vessel typologies with the same forms unearthed in different regions of Central Europe, as a starting point for a possible reconstruction of trade contacts between Italy and Central Europe. Archaeological contextualisation of the site and chrono-typological study of glass vessels were associated to ICP-MS (inductively coupled plasma mass spectrometry) and ICP-OES (inductively coupled plasma optical emission spectrometry) analyses, performed to characterise the composition of the glassy matrix (major and minor components as well as trace elements). The results, elaborated according to the archaeometric glass classification and provenancing of raw materials, shed new light on glass production in late Medieval times and can be broaden framed as a starting point for interpreting relations and exchanges between geographical areas and related cultures.     

PLS‐DA for compositional data with application to metabolomics

When quantifying information in metabolomics, the results are often expressed as data carrying only relative information. Vectors of these data have positive components, and the only relevant information is contained in the ratios between their parts; such observations are called compositional data. The aim of the paper is to demonstrate how partial least squares discriminant analysis (PLS‐DA)—the most widely used method in chemometrics for multivariate classification—can be applied to compositional data. Theoretical arguments are provided, and data sets from metabolomics are investigated. The data are related to the diagnosis of inherited metabolic disorders (IMDs). The first example analyzes the significance of the corresponding regression parameters (metabolites) using a small data set resulting from targeted metabolomics, where just a subset of potential markers is selected. The second example—the approach of untargeted metabolomics—was used for the analysis detecting almost 500 metabolites. The significance of the metabolites is investigated by applying PLS‐DA, accommodated according to a compositional approach. The significance of important metabolites (markers of diseases) is more clearly visible with the compositional method in both examples. Also, cross‐validation methods lead to better results in case of using the compositional approach. Copyright © 2014 John Wiley & Sons, Ltd.     

High-accuracy calculation of nuclear quadrupole moments of atomic halogens

Electric field gradients at the nuclei of halogen atoms are calculated using a finite field approach. The four-component Dirac-Coulomb Hamiltonian serves as the framework, all electrons are correlated by the relativistic Fock-space coupled cluster method with single and double excitations, and the Gaunt term, the main part of the Breit interaction, is included. Large basis sets (e.g., 28s24p21d9f4g2h Gaussian-type functions for I) are used. Combined with experimental nuclear quadrupole coupling constants, accurate estimates of the nuclear quadrupole moments are obtained. The calculated values are Q(35Cl)=-81.1(1.2) mb, Q(79Br)=302(5) mb, and Q(127I)=-680(10) mb. Currently accepted reference values [Pyykko, Mol. Phys. 99, 1617 (2001)] are -81.65(80), 313(3), and -710(10) mb, respectively. Our values are lower for the heavier halogens, corroborating the recent work of van Stralen and Visscher [Mol. Phys. 101, 2115 (2003)], who obtained Q(127I)=-696(12) mb in a series of molecular calculations.     

Influence of substituents on selectivity and efficiency of chiral separations of anions containing single nido-7,8-dicarbaundecaborane cluster with alpha-cyclodextrin

In background electrolyte (BGE) with the optimal methanol concentration of 30% (v/v), the ion with -NCS group bonded to a cluster boron atom exhibits the strongest interaction with alpha-cyclodextrin and the highest separation selectivity. Interaction of ions with alkyl or thioalkyl group weakens with the increasing substituent size. The ion with phenyl group exhibits the weakest interaction. Bonding of a group to boron atom weakens the ion interaction with alpha-cyclodextrin. Second substituent further weakens the interaction with alpha-cyclodextrin. Separation efficiency is lower at the presence of alpha-cyclodextrin than at its absence. This separation efficiency loss, amounts up to 90%.     

Partially O-alkylated thiacalix[4]arenes: synthesis, molecular and crystal structures, conformational behavior

NMR spectroscopy, X-ray diffraction analysis, and quantum chemical calculations were used for conformational behavior study of partially alkylated thiacalix[4]arenes bearing methyl (1), ethyl (2), or propyl (3) groups at the lower rim. The conformational properties are governed by two basic effects: (i) stabilization by intramolecular hydrogen bonds, and (ii) sterical requirements of the alkoxy groups at the lower rim. While the monosubstituted derivatives 1a and 3a adopt the cone conformation in solution, distally disubstituted compounds 1b, 1'b, 2b, 2'b, 3b, and 3'b exhibit several interesting conformational features. They prefer pinched cone conformation in solution, and, except for 3'b, they form also 1,2-alternate conformation, which is flexible and undergoes rather fast transition between two identical structures. The crystal structures of the compounds 1b, 2b, 2'b, and 3b revealed yet quite rare 1,2-alternate conformation forming molecular channels held together by pi-pi interactions. Different channels-with hexagonal symmetry, 0.26 nm wide-are formed in the crystal structure of the pinched cone conformation of 3b. An uncommon hydrogen bonding pattern was found in dimethoxy and dipropoxy derivatives 1'b and 3'b that adopt distorted cone conformations in crystal. Trialkoxy-substituted compounds 1c and 3c adopt the partial cone conformation in solution. A higher mobility of methyl derivative 1c enables also existence of the cone conformer.