An Electrochemical Study of the Surface Hybridization Process of Morpholino‐DNA: Thermodynamics and Kinetics

Morpholino (MO) is a neutral analogue of DNA, which shows promise in the development of DNA biosensors and diagnostic devices. The present study explores the hybridization process of a surface‐attached MO 22‐mer with 10‐mer and 20‐mer DNA targets on a gold electrode. The melting process of the MO‐DNA duplex at the electrode/buffer interface is recorded using cyclic voltammetry. These results show that the length of target DNA, the binding location of the target DNA on the surface‐immobilized MO chain, and electrostatic forces from neighbouring duplexes all modulate the stability and hybridization kinetics of the DNA targets with the MO probes. Melting temperatures for immobilized MO‐DNA duplexes are found to be insensitive to ionic strength, provided the duplexes do not have a linker. Although the melting temperature does not shift appreciably with ionic strength, the maximum hybridization yield does. This somewhat surprising observation is considered to originate from an electrostatic limit on the extent of attainable hybridization. It is also reported that hybridization tends to initiate at the upper half of MO probes.     

Solution properties of iron(III) complexes with 5-fluorosalicylic acid — spectra,speciation, and redox stability

Iron(III)-5-fluorosalicylic acid systems were investigated in water by pH potentiometry combined with UV-VIS spectrophotometry. The data revealed that stable aquated mono-, bis-, and tris(5-fluorosalicylato) iron(III) complexes are formed together with their monohydroxo and dihydroxo analogues. The stability constants of all present iron(III) species were calculated. Based on pH and the metal: ligand ratio dependent distribution of the species, electronic absorption spectra of the complexes in the visible region were obtained. Redox stability was monitored as an ability to undergo both spontaneous and photoinduced reduction of iron(III) to iron(II). Complexes do not undergo any redox changes when in dark neither in methanol nor in water. While aqueous solutions of complexes are stable under the influence of incident visible radiation, steady-state irradiation of the methanolic systems by visible light led to photoreduction of iron(III) to iron(II), the quantum yield of iron(II) photoformation was determined. Dedicated to Professor Milan Melník on the occasion of his 70th birthday     

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis,Characterization and ctDNA/HSA Spectroscopic Binding Properties

A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest K_b value (K_b = 3.18 × 10³ M⁻¹). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (K_SV = 2.26 M⁻¹, K_b = 2.54 M⁻¹), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.     

A Systematic Study of Coumarin–Tetrazine Light-Up Probes for Bioorthogonal Fluorescence Imaging

Fluorescent probes that light-up upon reaction with complementary bioorthogonal reagents are superior tools for no-wash fluorogenic bioimaging applications. In this work, a thorough study is presented on a set of seventeen structurally diverse coumarin–tetrazine probes that produce fluorescent dyes with exceptional turn-on ratios when reacted with trans-cyclooctene (TCO) and bicyclononyne (BCN) dienophiles. In general, formation of the fully aromatic pyridazine-containing dyes resulting from the reaction with BCN was found superior in terms of fluorogenicity. However, evaluation of the probes in cellular imaging experiments revealed that other factors, such as reaction kinetics and good cell permeability, prevail over the fluorescence turn-on properties. The best compound identified in this study showed excellent performance in live cell-labeling experiments and enabled no-wash fluorogenic imaging on a timescale of seconds.     

Tacrine-Coumarin Derivatives as Topoisomerase Inhibitors with Antitumor Effects on A549 Human Lung Carcinoma Cancer Cell Lines

A549 human lung carcinoma cell lines were treated with a series of new drugs with both tacrine and coumarin pharmacophores (derivatives 1a–2c) in order to test the compounds’ ability to inhibit both cancer cell growth and topoisomerase I and II activity. The ability of human topoisomerase I (hTOPI) and II to relax supercoiled plasmid DNA in the presence of various concentrations of the tacrine-coumarin hybrid molecules was studied with agarose gel electrophoresis. The biological activities of the derivatives were studied using MTT assays, clonogenic assays, cell cycle analysis and quantification of cell number and viability. The content and localization of the derivatives in the cells were analysed using flow cytometry and confocal microscopy. All of the studied compounds were found to have inhibited topoisomerase I activity completely. The effect of the tacrine-coumarin hybrid compounds on cancer cells is likely to be dependent on the length of the chain between the tacrine and coumarin moieties (1c, 1d = tacrine-(CH₂)_8–9-coumarin). The most active of the tested compounds, derivatives 1c and 1d, both display longer chains.     

Generalized interest rate dynamics and its impacts on finance and pensions

The recent global financial crisis caused implementation of negative or close to zero interest rates. This situation implies a necessity to study a flexible and simplistic model of interest rate, which well accommodates oscillations, cycles, and negative signs. In this article, we introduce a novel nonlinear stochastic interest rate model, which, as a special case, incorporates the standard linear model of Parker. Many practical implications for finance and pensions are obtained.     

Sensitive, label-free DNA diagnostics based on near-field microwave imaging

Biological assays often rely on "reporter labels" to enhance measurement sensitivity, for example, by incorporation of a fluorescent dye or a nanoparticle into a nucleic acid or a protein. Use of labels, however, complicates sample preparation, increases assay costs, and can cause experimental artifacts by interfering with assay thermodynamics or limiting label stability. We evaluate near-field microwave imaging (NFMI) as an alternative, label-free technique for molecular diagnostics. Using DNA monolayers as an experimental model, NFMI is demonstrated to achieve sensitivities comparable to conventional fluorescence bioassays. Moreover, NFMI is shown to be compatible with imaging at resolutions required by microarray applications, as demonstrated by monitoring DNA hybridization in an array format.     

On sieve-complete and compact-like spaces

It is shown that a completely regular space X is sieve-complete (or, equivalenty, X is the open image of a paracompact ?ech-complete space) iff βX?X is compact-like, i.e., Player I has a winning strategy in the topological game G(C, βX?X) of [13].