The study of the lipophilicity of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimidobutyramides using chromatographic and computational methods

The lipophilicity of the series of alpha-(4-phenylpiperazin-1-yl)-gamma-phthalimido-butyramides (1-8) has been investigated. Several methods, like reversed-phase thin-layer chromatography and high-performance liquid chromatography using reversed-phase RP18 and IAM.DD2 columns, were applied to determine RMO, log k0 and log k(0IAM) factors. The RP-TLC investigations were performed in mixtures of acetone-water and acetonitrile-water. For RP-HPLC method mixtures of acetonitrile, water and 0.01% TFA were used as the mobile phases while for IAM.DD2 investigations mixtures of acetonitrile and water were applied. The partition coefficients of compounds (1-8) were also calculated with the Pallas and CAChe programs. All the obtained data, both from experimental methods and computational calculations, were compared and a suitable conclusion was reached.     

Determination of major and trace elements in iron reference materials using k0-NAA

Major and trace element contents in iron ore reference materials were investigated using k ₀-instrumental neutron activation analysis (k ₀-INAA). To avoid iron interferences, radiochemical separation was developed (k ₀-RNAA). The determination of the investigated elements in the inorganic phase from hydrochloric acid solution was performed after radiochemical separation of iron by diisopropyl ether. It was found that after the Fe elimination, the limit of detection for some elements was much lower that enables their direct determination. The distribution of 39 elements (with intermediate/medium and long half-life radionuclides) after Fe removal was investigated.     

Competition between the albumin and three histidine fragment of amyloid precursor protein sites to bind Cu(II)

The aim of this work was to check experimentally the relationship between the five-nitrogen donor system {3 × N_imid, 2 × N⁻} seen e.g. in the peptide fragments of the cysteine-rich amyloid precursor protein (APP) region and the albumin-like {NH₂, 2 × N⁻, N_imid} coordination site. The protected and unprotected octadecapeptides DAHQERMDVSETHLHWHT and Ac-DAHQERMDVSETHLHWHT-NH₂ were synthesized and potentiometric and spectroscopic studies were performed. A comparison of both metal-binding sites that occur in both peptides clearly shows that in the unprotected ligand albumin-like binding is much more efficient than the three His site, although around pH 5 both sites have a comparable ability to bind the Cu(II) ion. However, a comparison of the protected and unprotected peptides with their metal binding sites clearly shows that the three His site is very efficient in binding Cu(II) although less effective than the albumin-like motif.     

Spectral Properties and Solubilization Location of 2'-Ethylhexyl 4-(N,N-Dimethylamino)benzoate in Micelles

Dual fluorescence and UV absorption of 2'-ethylhexyl 4-(N,N-dimethylamino)benzoate (EHDMAB) were investigated in cationic, non-ionic and anionic micelles. When EHDMAB was solubilized in different micelles, the UV absorption of EHDMAB was enhanced. Twisted intramolecular charge transfer (TICT) emission with longer wavelength was observed in ionic micelles, whereas TICT emission with shorter wavelength was obtained in non-ionic micelles. In particular, dual fluorescence of EHDMAB was significantly quenched by the positively charged pyridinium ions arranged in the Stern layer of cationic micelles. UV radiation absorbed mainly decays via TICT emission and radiationless deactivation. The dimethylamino group of EHDMAB experiences different polar environments in ionic and non-ionic micelles according to the polarity dependence of TICT emission of EHDMAB in organic solvents. In terms of the molecular structures and sizes of EHDMAB and surfactants, each individual EHDMAB molecule should be buried in micelles with its dimethylamino group toward the polar head groups of different micelles and with its 2'-ethylhexyl chain toward the hydrophobic micellar core. Dynamic fluorescence quenching measurements of EHDMAB provide further support for the location of EHDMAB in different micelles.     

Simultaneous determination of rosiglitazone and metformin in plasma by gradient liquid chromatography with UV detection

A novel, fast and simple liquid chromatographic method was developed and validated for the simultaneous determination of rosiglitazone and metformin in human plasma. The analysis was performed on a phenyl column (250 mm × 4.6 mm i.d., 5 μm) using a gradient method starting with mobile phase composed of acetonitrile:5 mM acetate buffer pH 5.5 (75:25, v/v). The flow rate was 1 mL min⁻¹. UV detection was performed at 245 nm and verapamil was used as internal standard. The total run time was less than 10 min. Sample preparation included a simple protein precipitation step with acetonitrile. Validation experiments were performed to demonstrate stability, specificity, sensitivity, linearity, accuracy, precision and robustness. The limit of quantification was 100 ng mL⁻¹ for rosiglitazone and 250 ng mL⁻¹ for metformin. The extraction recoveries were 100.02-105.0% for rosiglitazone and 105.64-103.88% for metformin. The method was applied with success to plasma samples obtained from diabetic patients undergoing treatment with rosiglitazone and metformin.     

Topological insights in polynuclear Ni/Na coordination clusters derived from a schiff base ligand

This article presents the syntheses, crystal structures, topological features and magnetic properties of two Ni^II/Na^I coordination clusters formulated [Ni ₃ ^II Na(L1)₃(HL1)(MeOH)₂] (1) and [Ni ₆ ^II Na(L1)₅(CO₃)(MeO)(MeOH)₃(H₂O)₃]·4(MeOH) 2(H₂O) [2 4(MeOH) 2(H₂O)] where H₂L1 is the semi-rigid Schiff base ligand (E)-2-(2-hydroxy-3-methoxybenzylideneamino)-phenol). Compound 1 possesses a rare Ni ₃ ^II Na^I cubane (3M4-1) topology, and compound 2 is the first example in polynuclear Ni/Na chemistry that exhibits a 2,3,4M7-1 topology.     

Gapmer Antisense Oligonucleotides Containing 2′,3′-Dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-d-lyxofuranosyl Nucleotides Display Site-Specific RNase H Cleavage and Induce Gene Silencing

Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing.     

Solid-State Dynamics and High-Pressure Studies of a Supramolecular Spiral Gear

The structures and solid-state dynamics of the supramolecular salts of the general formula [(12-crown-4)₂ ⋅ DABCOH₂](X)₂ (where DABCO=1,4-diazabicyclo[2.2.2]octane, X=BF₄, ClO₄) have been investigated as a function of temperature (from 100 to 360 K) and pressure (up to 3.4 GPa), through the combination of variable-temperature and variable-pressure XRD techniques and variable-temperature solid-state NMR spectroscopy. The two salts are isomorphous and crystallize in the enantiomeric space groups P3₂2₁ and P3₁2₁. All building blocks composing the supramolecular complex display dynamic processes at ambient temperature and pressure. It has been demonstrated that the motion of the crown ethers is maintained on lowering the temperature (down to 100 K) or on increasing the pressure (up to 1.5 GPa) thanks to the correlation between neighboring molecules, which mesh and rotate in a concerted manner similar to spiral gears. Above 1.55 GPa, a collapse-type transition to a lower-symmetry ordered structure, not attainable at a temperature of 100 K, takes place, proving, thus, that the pressure acts as the means to couple and decouple the gears. The relationship between temperature and pressure effects on molecular motion in the solid state has also been discussed.