Photochemical Reactivity of Naphthol-Naphthalimide Conjugates and Their Biological Activity

Quinone methide precursors 1a–e, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (Φ_F ≈ 10⁻²). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (Φ_R ≈ 10⁻⁵). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that 1a and 1e form complexes with ct-DNA with moderate association constants K_a ≈ 10⁵–10⁶ M⁻¹, as well as with bovine serum albumin (BSA) K_a ≈ 10⁵ M⁻¹ (1:1 complex). The irradiation of the complex 1e@BSA resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of 1a–e against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for 1e (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light.     

Zeros of certain Drinfeld modular functions

For every positive integer m, there is a unique Drinfeld modular function, holomorphic on the Drinfeld upper-half plane, jm(z) with the following t-expansion

     

A thermoreversible double gel: characterization of a methylcellulose and kappa-carrageenan mixed system in water by SAXS, DSC and rheology

Sol-gel and gel-sol thermal transition of methylcellulose/water, kappa-carrageenan/water and methylcellulose/kappa-carrageenan/water mixtures was investigated utilizing small-angle X-ray scattering (SAXS), differential scanning calorimetry (DSC) and oscillatory rheological experiments in temperature regime from 20 to 80 degrees C. Methylcellulose (E461) and kappa-carrageenan (E407) are well-known additives used for gelation in various nutrition and other products. The formulation and characterization of a mixed thermoreversible methylcellulose/kappa-carrageenan/water gel with very interesting double thermal transition gel-sol-gel upon heating was possible. This specific thermal behavior provides a liquid state of the system between the low-temperature and high-temperature gel-state and at the same time allows for the easy temperature tuning of the system's state. As such this system is suggested to be further tested as potential carrier for various functional colloidal systems.     

A General Strategy to Access Structural Information at Atomic Resolution in Polyglutamine Homorepeats

Homorepeat (HR) proteins are involved in key biological processes and multiple pathologies, however their high‐resolution characterization has been impaired due to their homotypic nature. To overcome this problem, we have developed a strategy to isotopically label individual glutamines within HRs by combining nonsense suppression and cell‐free expression. Our method has enabled the NMR investigation of huntingtin exon1 with a 16‐residue polyglutamine (poly‐Q) tract, and the results indicate the presence of an N‐terminal α‐helix at near neutral pH that vanishes towards the end of the HR. The generality of the strategy was demonstrated by introducing a labeled glutamine into a pathological version of huntingtin with 46 glutamines. This methodology paves the way to decipher the structural and dynamic perturbations induced by HR extensions in poly‐Q‐related diseases. Our approach can be extended to other amino acids to investigate biological processes involving proteins containing low‐complexity regions (LCRs).     

Depletion of high-abundance proteins from human plasma using a combination of an affinity and pseudo-affinity column

Human serum albumin (HSA) and immunoglobulin G (IgG) represent over 75% of all proteins present in human plasma. These high-abundance proteins prevent the detection of low-abundance proteins which are potential markers for various diseases. The depletion of HSA and IgG is therefore essential for further proteome analysis. In this paper we describe the optimization of conditions for selective depletion of HSA and IgG using affinity and pseudo-affinity chromatography. A BIA Separations CIM (convective interaction media) Protein G disk was applied for the removal of IgG and the Mimetic Blue SA A6XL stationary phase for the removal of HSA. The binding and the elution buffer for CIM Protein G disk were chosen on the basis of the peak shape. The dynamic binding capacity was determined. It was shown to be dependent on the buffer system used and independent of the flow rate and of the concentration of IgG. Beside the binding capacity for the IgG standard, the binding capacity was also determined for IgG in human plasma. The Mimetic Blue SA A6XL column was characterized using human plasma. The selectivity of the depletion was dependent on the amount of human plasma that was loaded on the column. After the conditions on both supports had been optimized, the Mimetic Blue SA A6XL stationary phase was combined with the CIM Protein G disk in order to simultaneously deplete samples of human plasma. A centrifuge spin column that enables the removal of IgG and HSA from 20 μL of human plasma was designed. The results of the depletion were examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis.     

Non-destructive dating of fiber-based gelatin silver prints using near-infrared spectroscopy and multivariate analysis

An innovative approach to date fiber-based gelatin silver prints using near-infrared spectroscopy (NIR) and multivariate analysis is presented. NIR spectra were acquired for 152 film stills printed in the USA between 1914 and 1986, and partial least square (PLS) analysis was used to correlate the spectra with the year the photographs were printed. Principal component analysis and spectral interpretation helped clarify the underlying correlation between the print date and the composition and ageing of the photographic papers. The method was successfully validated with an independent set of 66 film stills printed in the USA, and a prediction error (root mean square error of prediction) of 6 years was achieved. The method was also tested on films stills printed in Germany and Russia, as well as amateur prints and photographs in the collection of the Museum of Modern Art. The prediction error was significantly larger, with the exception of the amateur prints, due to differences in the composition and/or properties of the papers depending on their geographical origin and purpose as confirmed by discriminant analysis.     

Tebrophen--an old polyphenol drug with anticancer potential

In vitro high-throughput screening was carried out in order to detect new activities for old drugs and to select compounds for the drug development process comprising new indications. Tebrophen, a known antiviral drug, was found to inhibit activities on inflammation and cancer related targets. In primary screening this semisynthetic halogenated polyphenol was identified to inhibit the activities of kinases ZAP-70 and Lck (IC?? 0.34 μM and 16 μM, respectively), as well as hydrolase DPPIV (at 80 μM 41% inhibition). Next, it showed no cytotoxic effects on standard cell lines within 24 h. However, tebrophen slowed propagation of breast cancer (MDA-MB-231), osteosarcoma (U2OS) and cervical carcinoma (HeLa), through at least 35 population doublings in a dose-dependent manner. It completely stopped the division of the prostate cancer (PC3) cell line at 50 μM concentration and the cells entered massive cell death in less than 20 days. On the other hand, tebrophen did not influence the growth of normal fibroblasts. According to the measured oxidative burst and estimated in silico parameters its direct antioxidative ability is limited. The obtained results indicate that tebrophen can be considered a promising lead molecule for generating more soluble derivatives with specific anticancer efficacy.     

An improved bound for disjoint directed cycles

We show that every directed graph with minimum out-degree at least $18k$ contains at least $k$ vertex disjoint cycles. This is an improvement over the result of Alon who showed this result for digraphs of minimum out-degree at least $64k$. The main benefit of the argument is that getting better results for small values of $k$ allows for further improvements to the constant.     

Osmotic and volume properties of stereoregular poly(methacrylic acids) in aqueous solution: role of intermolecular association

Osmotic coefficients, phi, and apparent molar volumes, PhiV, of aqueous solutions of isotactic, syndiotactic, and atactic poly(methacrylic acid), i-PMA, s-PMA, and a-PMA, respectively, were measured at 298 K in dependence on polymer concentration and on degree of neutralization, alphaN, of carboxyl groups. The solutions of i-PMA have lower phi values than those of a-PMA and s-PMA in the whole region of alphaN. Molecular dynamics simulation studies of the isotactic and the syndiotactic PMA 101-mer have shown that lower phi is a consequence of a shorter distance between charges, which leads to a greater charge density of the isotactic polymer and thus to stronger binding of counterions. The experimental phi data were analyzed using a cylindrical cell model. Good agreement between theory and experiment was achieved when charges on the polyion were distributed periodically along the z-axis of the polyion in accordance with the simulation results. The alphaN dependence of the PhiV data pointed out that all PMA isomers bind an appreciable amount of water in the elementary dissociation process (electrostriction). For a- and s-PMA, the PhiV values decrease linearly with increasing alphaN, whereas they show a marked nonlinear dependence in the case of i-PMA for alphaN < 0.6. The latter finding was ascribed to a very high intermolecular association tendency of the isotactic polymer. This association tendency of PMA chains was confirmed by light scattering measurements. It is present in both i- and a-PMA solutions but is much more pronounced in the i-PMA case.     

The Role of Triazole and Glucose Moieties in Alkali Metal Cation Complexation by Lower-Rim Tertiary-Amide Calix[4]arene Derivatives

The binding of alkali metal cations with two tertiary-amide lower-rim calix[4]arenes was studied in methanol, N,N-dimethylformamide, and acetonitrile in order to explore the role of triazole and glucose functionalities in the coordination reactions. The standard thermodynamic complexation parameters were determined microcalorimetrically and spectrophotometrically. On the basis of receptor dissolution enthalpies and the literature data, the enthalpies for transfer of reactants and products between the solvents were calculated. The solvent inclusion within a calixarene hydrophobic basket was explored by means of ¹H NMR spectroscopy. Classical molecular dynamics of the calixarene ligands and their complexes were carried out as well. The affinity of receptors for cations in methanol and N,N-dimethylformamide was quite similar, irrespective of whether they contained glucose subunits or not. This indicated that sugar moieties did not participate or influence the cation binding. All studied reactions were enthalpically controlled. The peak affinity of receptors for sodium cation was noticed in all complexation media. The complex stabilities were the highest in acetonitrile, followed by methanol and N,N-dimethylformamide. The solubilities of receptors were greatly affected by the presence of sugar subunits. The medium effect on the affinities of calixarene derivatives towards cations was thoroughly discussed regarding the structural properties and solvation abilities of the investigated solvents.