Silk-based nanocomplexes with tumor-homing peptides for tumor-specific gene delivery

Nanoscale complexes of recombinant silk molecules containing THPs with DNA are designed as less cytotoxic and highly target‐specific gene carriers. Genetically engineered silk proteins containing poly(L ‐lysine) domains to interact with pDNA and the THP to bind to specific tumorigenic cells for target‐specific pDNA delivery are prepared, followed by in vitro transfection into MDA‐MB‐435 melanoma cells, highly metastatic human breast tumor MDA‐MB‐231 cells, and non‐tumorigenic MCF‐10A breast epithelial cells. The silk/poly(L ‐lysine) block copolymer containing Lyp1 (ML‐Lyp1) shows significant differences from silk/poly(L ‐lysine) block copolymer containing F3 (ML‐F3) in cytotoxicity to MCF10A cells. ML‐F3 is the most promising candidate for target delivery into tumorigenic cells.

     

E–mv coupling of vibrational overtone in organic conductors: Relationship to optical nonlinearities and ferroelectricity

A strong electron–phonon coupling effect, referred to as electron–molecular vibration (e–mv) coupling, induces characteristic vibronic signals in the vibrational spectra of organic conductors. This paper discusses a new spectroscopic signal induced by the e–mv coupling effect, and the physical implications of its emergence. This vibronic signal, attributable to an overtone of a molecular vibration, appears with an anti-resonance form in the infrared spectrum of some mixed-valency complexes when the compounds undergo a charge-ordering transition. Based on the results of cluster model calculations, the activation of the overtone signal is interpreted as an indication of the generation of anharmonicity in the electronic potential. This analysis suggests that the series of the complexes should possess potential nonlinear optical abilities, though these compounds have long been viewed as electric conductors having the opposite characteristics of dielectrics that show nonlinear optical properties.     

Hydrogen bonding as a modulator of aromaticity and electronic structure of selected ortho-hydroxybenzaldehyde derivatives

Properties of hydrogen bonds can induce changes in geometric or electronic structure parameters in the vicinity of the bridge. Here, we focused primarily on the influence of intramolecular H-bonding on the molecular properties in selected ortho-hydroxybenzaldehydes, with additional restricted insight into substituent effects. Static models were obtained in the framework of density functional theory at B3LYP/6-311+G(d,p) level. The electronic structure parameters evolution was analyzed on the basis of Atoms In Molecules (AIM) and Natural Bond Orbitals methods. The aromaticity changes related to the variable proton position and presence of substituents were studied using Harmonic Oscillator Model of Aromaticity (HOMA), Nucleus-Independent Chemical Shift (NICS) and AIM-based parameter of Matta and Hernández-Trujillo. Finally, Car-Parrinello molecular dynamics was applied to study variability of the hydrogen bridge dynamics. The interplay between effects of the substitution and variable position of the bridged proton was discussed. It was found that the hydrogen bond energies are ca. 9-10 kcal/mol, and the bridged proton exhibits some degree of penetration into the acceptor region. The covalent character of the studied hydrogen bond was most observable when the bridged proton reached the middle position between the donor and acceptor regions. The aromaticity indexes showed that the aromaticity of the central phenyl ring is strongly dependent on the bridged proton position. Correlations between these parameters were found and discussed. In the applied time-scale, the analysis of time evolution of geometric parameters showed that the resonance strengthening does not play a crucial role in the studied compounds.     

Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging

Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively.     

Volumetric properties of binary mixtures of alcoxyethanols with tert-butyl ethyl ether at various temperatures

Densities at 293.15, 298.15, 303.15, 308.15 and 313.15 K of the binary liquid mixtures made of tert-butyl ethyl ether with either 2-ethoxyethanol, or 2-(2-ethoxy)ethoxyethanol, or 2-[2-(2-ethoxy)ethoxy]ethoxyethanol have been measured over the whole mixture compositions. These data have been used to compute the excess molar volumes (V^E). The excess molar volumes always are negative over the entire range of composition for all the binary mixtures investigated. The changes of V^E with variations of the composition and the chain-length of the alkyl groups in the alkoxyethanol molecules are discussed in terms of possible intermolecular interactions.     

New procedure of selected biogenic amines determination in wine samples by HPLC

A new procedure for determination of biogenic amines (BA): histamine, phenethylamine, tyramine and tryptamine, based on the derivatization reaction with 2-chloro-1,3-dinitro-5-(trifluoromethyl)-benzene (CNBF), is proposed. The amines derivatives with CNBF were isolated and characterized by X-ray crystallography and ¹H, ¹³C, ¹⁹F NMR spectroscopy in solution. The novelty of the procedure is based on the pure and well-characterized products of the amines derivatization reaction. The method was applied for the simultaneous analysis of the above mentioned biogenic amines in wine samples by the reversed phase-high performance liquid chromatography. The procedure revealed correlation coefficients (R²) between 0.9997 and 0.9999, and linear range: 0.10–9.00 mg L⁻¹ (histamine); 0.10–9.36 mg L^-1 (tyramine); 0.09–8.64 mg L⁻¹ (tryptamine) and 0.10–8.64 mg L⁻¹ (phenethylamine), whereas accuracy was 97%–102% (recovery test). Detection limit of biogenic amines in wine samples was 0.02–0.03 mg L⁻¹, whereas quantification limit ranged 0.05–0.10 mg L⁻¹. The variation coefficients for the analyzed amines ranged between 0.49% and 3.92%. Obtained BA derivatives enhanced separation the analytes on chromatograms due to the inhibition of hydrolysis reaction and the reduction of by-products formation.     

Reversible Reduction of Oxatriphyrin(3.1.1)—Adjusting the Coordination Abilities to the Central Ion

Furan‐fused oxatriphyrin(3.1.1) acts as a ligand towards boron(III), phosphorous(III), and phosphorous(V) ions. The coordination abilities are adjusted by changes of the oxidation state. Two coordination modes are possible, depending on the central‐ion entrapped in the oxatriphyrin(3.1.1) environment. A free base, structurally similar to the complexes, can be easily obtained by regioselective reduction. The resulting molecules are highly emissive after conversion into a phlorin‐like oxatriphyrin(3.1.1) frame (NON donors), and show chiral activity caused by the presence of a tetrahedral carbon.     

Heterocyclic tautomerism: reassignment of two crystal structures of 2‐amino‐1,3‐thiazolidin‐4‐one derivatives

The structures of 5‐(2‐hydroxyethyl)‐2‐[(pyridin‐2‐yl)amino]‐1,3‐thiazolidin‐4‐one, C₁₀H₁₁N₃O₂S, (I), and ethyl 4‐[(4‐oxo‐1,3‐thiazolidin‐2‐yl)amino]benzoate, C₁₂H₁₂N₂O₃S, (II), which are identical to the entries with refcodes GACXOZ [Váňa et al. (2009). J. Heterocycl. Chem. 46 , 635–639] and HEGLUC [Behbehani & Ibrahim (2012). Molecules, 17 , 6362–6385], respectively, in the Cambridge Structural Database [Allen (2002). Acta Cryst. B 58 , 380–388], have been redetermined at 130 K. This structural study shows that both investigated compounds exist in their crystal structures as the tautomer with the carbonyl–imine group in the five‐membered heterocyclic ring and an exocyclic amine N atom, rather than the previously reported tautomer with a secondary amide group and an exocyclic imine N atom. The physicochemical and spectroscopic data of the two investigated compounds are the same as those of GACXOZ and HEGLUC, respectively. In the thiazolidin‐4‐one system of (I), the S and chiral C atoms, along with the hydroxyethyl group, are disordered. The thiazolidin‐4‐one fragment takes up two alternative locations in the crystal structure, which allows the molecule to adopt R and S configurations. The occupancy factors of the disordered atoms are 0.883 (2) (for the R configuration) and 0.117 (2) (for the S configuration). In (I), the main factor that determines the crystal packing is a system of hydrogen bonds, involving both strong N—H...N and O—H...O and weak C—H...O hydrogen bonds, linking the molecules into a three‐dimensional hydrogen‐bond network. On the other hand, in (II), the molecules are linked via N—H...O hydrogen bonds into chains.     

A nonradioactive electrophoretic mobility shift assay for measurement of pregnane X receptor binding activity to CYP3A4 response element

The electrophoretic mobility shift assay (EMSA) is a method for the study of specific DNA–protein interactions in vitro. The pregnane X receptor (PRX) is a key xenobiotic sensor that regulates the expression of drug‐metabolizing enzymes and many other genes. Radiolabeled ³²P‐DNA‐probes had been used in studies of PXR‐DNA interactions. There is an increasing need for nonradioactive assays, due to the health, safety and environmental issues. In the current study, we present a protocol for the nonradioactive electrophoretic mobility shift assay, allowing studying interactions between human PXR with promoter DNA sequences.     

On Complex Formation between 5-Fluorouracil and β-Cyclodextrin in Solution and in the Solid State: IR Markers and Detection of Short-Lived Complexes by Diffusion NMR

In this work, the nuclear magnetic resonance (NMR) and IR spectroscopic markers of the complexation between 5-fluorouracil (5-FU) and β-cyclodextrin (β-CD) in solid state and in aqueous solution are investigated. In the attenuated total reflectance(ATR) spectra of 5-FU/β-CD products obtained by physical mixing, kneading and co-precipitation, we have identified the two most promising marker bands that could be used to detect complex formations: the C=O and C-F stretching bands of 5-FU that experience a blue shift by ca. 8 and 2 cm⁻¹ upon complexation. The aqueous solutions were studied by NMR spectroscopy. As routine NMR spectra did not show any signs of complexation, we have analyzed the diffusion attenuation of spin–echo signals and the dependence of the population factor of slowly diffusing components on the diffusion time (diffusion NMR of pulsed-field gradient (PFG) NMR). The analysis has revealed that, at each moment, ~60% of 5-FU molecules form a complex with β-CD and its lifetime is ca. 13.5 ms. It is likely to be an inclusion complex, judging from the independence of the diffusion coefficient of β-CD on complexation. The obtained results could be important for future attempts of finding better methods of targeted anticancer drug delivery.