Synthesis of new (arylcarbonyloxy)aminopropanol derivatives and the determination of their physico-chemical properties

Eight hydrochlorides of 3-{2-[(2/4-fluorophenoxy)-ethylamino]}-2-hydroxypropyl-4-alkoxybenzoates and four hydrochlorides of 3-tert-butylamino-2-hydroxypropyl-4-butoxybenzoates were prepared as potential antagonists of the β₁-adrenergic receptor (beta-blockers). A multistep synthesis of these compounds is described as well as their detailed analytical characterization. The pharmacokinetic properties of these weak base compounds are significantly influenced by their acid-base dissociation constant, pK _a. The knowledge of this value is crucial for new drug development. This paper is aimed at developing a methodology that utilizes pH-dependent ¹H NMR spectroscopy for its routine analysis. The selected predicted physico-chemical parameters of the new (arylcarbonyloxy)aminopropanols (i.e., aryloxyaminopropanol derivatives) were compared with the model drugs esmolol and flestolol.      

Doxorubicin Encapsulation Investigated by Capillary Electrophoresis with Laser-Induced Fluorescence Detection

Doxorubicin (DOX) belongs to the group of anthracycline antibiotics with very effective anticancer properties. On the other hand, the cardiotoxic effects limit its application over the maximum cumulative dose. To overcome this obstacle, encapsulation of this drug into the protective nanotransporter such as apoferritin is beneficial. In this study, fluorescent behavior of DOX in various solvents was determined by fluorescence spectrometry, demonstrating the fluorescence quenching effect of water, which is often used as a solvent. It was found that by increasing the amount of the organic phase in the DOX solvent the dynamic quenching is significantly suppressed. Ethanol, acetonitrile and dimethyl sulfoxide were tested and the best linearity of the calibration curve was obtained when above 50 % of the solvent was present in the binary mixture with water. Moreover, pH influence on the DOX fluorescence was also observed within the range of 4–10. Two times higher fluorescence intensity was observed at pH 4 compared to pH 10. Further, the DOX behavior in capillary electrophoresis (CE) was investigated. Electrophoretic mobilities (CE) in various pH of the background electrolyte were determined within the range from 16.3 to −13.3 × 10 ⁻⁹ m⁻² V⁻¹ s⁻¹. Finally, CE was also used to monitor the encapsulation of DOX into the cavity of apoferritin as well as the pH-triggered release.

     

Dynamic Structures of DNA Heptamers with Different Central Trinucleotide Sequences Studied by Electrochemical and Spectral Methods

A short, single‐stranded DNA fragment d(GCGAAGC) and its analogs d(GCNNNGC) carrying different trinucleotide sequences in the center of the molecule (AAA,CCC, GGG or TTT) were investigated by spectral (CD and UV spectra) and electrochemical methods (voltammetry, polyacrylamide gel electrophoresis). Our results show that (i) the central triplet GAA or AAA dramatically stabilizes DNA hairpins, (ii) a stem‐loop configuration is not supported by CCC or TTT sequences, instead, these heptamers adopt bimolecular duplex forms. Finally (iii), in the case of GGG sequence a very stable supramolecular G‐quadruplex is formed.     

Molecular beam study of CO chemisorption on alumina-supported Pd particles

The adsorption of carbon monoxide on small alumina-supported Pd particles and on a Pd(111) single crystal has been studied with a molecular beam techniques. The measured sticking coefficient shows that CO adsorbs on palladium surface according to precursor states. It is noted that a temperature dependent diffusion of gas molecules on the support influences the sticking probability of CO.     

Evidence for the two-body nature of theE1 transition operator in the sdf-interacting boson model

Two new absolute transition rates are reported for the nucleus¹⁴⁴Sm following an (α, α′) Coulomb excitation study. They are B(E3; 3^?→ 0⁺)=(38±3) W.u. and B(E1;3^? → 2⁺)=(2.8±0.4)×10^?3 W.u. This large E1 matrix element, along with the previously known B(E1; 1^? →⁺) value support the interpretation of the 1^? state in this nucleus as 2-phonon 2⁺ × 3^? excitation. In the frame of the IBM-1 +f-boson model we show the need for a two-body term in the E1 transition operator. Estimates for the strengths of the one and two-body parts of the E1 transition operator are obtained from these experimental data.     

Design of molecular imprinted polymers compatible with aqueous environment

The main problem of poor water compatibility of molecularly imprinted polymers (MIPs) was addressed in examples describing design of synthetic receptors with high affinity for drugs of abuse. An extensive potentiometric titration of 10 popular functional monomers and corresponding imprinted and Blank polymers was conducted in order to evaluate the subtleties of functional groups ionisation under aqueous conditions. It was found that polymers prepared using 2-trifluoromethacrylic acid (TFMAA) in combination with toluene as porogen possess superior properties which make them suitable for effective template recognition in water. The potential impact of phase separation during polymerisation on formation of high quality imprints has been discussed. Three drugs of abuse such as cocaine, deoxyephedrine and methadone were used as template models in polymer preparation for the practical validation of obtained results. The polymer testing showed that synthesized molecularly imprinted polymers have high affinity and selectivity for corresponding templates in aqueous environment, with imprinting factors of 2.6 for cocaine and 1.4 for methadone and deoxyephedrine. Corresponding Blank polymers were unable to differentiate between analytes, suggesting that imprinting phenomenon was responsible for the recognition properties.     

Stability constants of amino acids, peptides, proteins, and other biomolecules determined by CE and related methods: recapitulation of published data

The stability (affinity, association, binding, complexation, formation) constant characterizes binding interaction between the analyte and the complexing agent. Knowledge of the stability constant makes possible the prediction and estimation of the binding behavior of constituents (amino acids, peptides, proteins, drugs, antibiotics, enzymes, enantiomers) to their partners, and the finding of a suitable partner for the given analyte to form a stable complex. The present paper summarizes the stability constant determination methods and the approaches used to evaluate the experimental data. Further, the paper recapitulates the published stability constant values determined, mainly, by capillary electrophoretic methods, taken from the Web of Science database covering the last decade. Details of the experimental conditions employed for the determination of the stability constants are also given. The review attempts to give a critical evaluation of the problems that accompany the determination of stability constant and discusses their solution.     

Hydrogenation of coumarin to octahydrocoumarin over a Ru/C catalyst

The production of octahydrocoumarin, which can serve as a replacement for toxic coumarin, was investigated using 5% Ru on active carbon (Ru/C) as the catalyst for the hydrogenation of couma-rin. The hydrogenation was studied by optimizing the reaction conditions (pressure, solvent and coumarin concentration). The activity and selectivity of the Ru/C catalyst were compared for dif-ferent solvents. The mechanism of coumarin hydrogenation was deduced. The formation of side products was explained. The optimal hydrogenation reaction conditions were: 130 °C, 10 MPa, 60 wt% coumarin in methanol, and 0.5 wt% (based on coumarin) of Ru/C catalyst. At the complete conversion of coumarin, the selectivity to the desired product was 90%.     

From Dibismuthenes to Three‐ and Two‐Coordinated Bismuthinidenes by Fine Ligand Tuning: Evidence for Aromatic BiC3N Rings through a Combined Experimental and Theoretical Study

The reduction of N,C,N‐chelated bismuth chlorides [C₆H₃‐2,6‐(CH?NR)₂]BiCl₂ [where R=tBu ( 1 ), 2′,6′‐Me₂C₆H₃ ( 2 ), or 4′‐Me₂NC₆H₄ ( 3 )] or N,C‐chelated analogues [C₆H₂‐2‐(CH?N‐2′,6′‐iPr₂C₆H₃)‐4,6‐(tBu)₂]BiCl₂ ( 4 ) and [C₆H₂‐2‐(CH₂NEt₂)‐4,6‐(tBu)₂]BiCl₂ ( 5 ) is reported. Reduction of compounds 1 – 3 gave monomeric N,C,N‐chelated bismuthinidenes [C₆H₃‐2,6‐(CH?NR)₂]Bi [where R=tBu ( 6 ), 2′,6′‐Me₂C₆H₃ ( 7 ) or 4′‐Me₂NC₆H₄ ( 8 )]. Similarly, the reduction of 4 led to the isolation of the compound [C₆H₂‐2‐(CH?N‐2′,6′‐iPr₂C₆H₃)‐4,6‐(tBu)₂]Bi ( 9 ) as an unprecedented two‐coordinated bismuthinidene that has been structurally characterized. In contrast, the dibismuthene {[C₆H₂‐2‐(CH₂NEt₂)‐4,6‐(tBu)₂]Bi}₂ ( 10 ) was obtained by the reduction of 5 . Compounds 6 – 10 were characterized by using ¹H and ¹³C NMR spectroscopy and their structures, except for 7 , were determined with the help of single‐crystal X‐ray diffraction analysis. It is clear that the structure of the reduced products (bismuthinidene versus dibismuthene) is ligand‐dependent and particularly influenced by the strength of the N→Bi intramolecular interaction(s). Therefore, a theoretical survey describing the bonding situation in the studied compounds and related bismuth(I) systems is included. Importantly, we found that the C₃NBi chelating ring in the two‐coordinated bismuthinidene 9 exhibits significant aromatic character by delocalization of the bismuth lone pair.     

On families of quadrature formulas based on Euler identities

A family consisting of quadrature formulas which are exact for all polynomials of order ?5 is studied. Changing the coefficients, a second family of quadrature formulas, with the degree of exactness higher than that of the formulas from the first family, is produced. These formulas contain values of the first derivative at the end points of the interval and are sometimes called “corrected”.