Multifaceted Studies of the DNA Interactions and In Vitro Cytotoxicity of Anticancer Polyaromatic Platinum(II) Complexes

This study reports a detailed biophysical analysis of the DNA binding and cytotoxicity of six platinum complexes (PCs). They are of the type [Pt(P_L)(SS‐dach)]Cl₂, where P_L is a polyaromatic ligand and SS‐dach is 1S,2S‐diaminocyclohexane. The DNA binding of these complexes was investigated using six techniques including ultraviolet and fluorescence spectroscopy, linear dichroism, synchrotron radiation circular dichroism, isothermal titration calorimetry and mass spectrometry. This portfolio of techniques has not been extensively used to study the interactions of such complexes previously; each assay provided unique insight. The in vitro cytotoxicity of these compounds was studied in ten cell lines and compared to the effects of their R,R enantiomers; activity was very high in Du145 and SJ‐G2 cells, with some submicromolar IC₅₀ values. In terms of both DNA affinity and cytotoxicity, complexes of 5,6‐dimethyl‐1,10‐phenanthroline and 2,2′‐bipyridine exhibited the greatest and least activity, respectively, suggesting that there is some correlation between DNA binding and cytotoxicity.     

Phase topology of Appelrot class I of a Kowalewski top in a magnetic field

We consider an integrable case generalizing the Appelrot class I of a Kowalewski top in a magnetic field. Its phase topology is investigated by means of Fomenko-Zieschang invariants. The offered method of approach to the calculation of marks completes Bolsinov’s method in the situation where it is not usable. __________ Translated from Fundamentalnaya i Prikladnaya Matematika, Vol. 12, No. 1, pp. 95–128, 2006.     

Effect of acetate and EDTA ligands on Hydrolysis of the Iron(III) Ion in sodium chloride medium

The hydrolysis of the iron(III) ion in sodium chloride medium without organic ligands and in the presence of acetate and EDTA ligands was studied by emf method, at 25°C. The data indicate the effect of the organic ligands. In the presence of acetate ion the beginning of hydrolysis of the iron(III) ion is slightly shifted toward lower pH values, while in the presence of EDTA, as a strong complex forming ligand, the beginning of hydrolysis is shifted toward higher pH values for 2.5 pH units.     

Photolyse von Monochloressigsäure bei 253,7 nm in wäßriger Lösung

The photolysis of 0.5 mole/l monochloroacetic acid in aqueous solution at 253.7 nm was studied and as products were determined: Cl^? (?=0.34), CH₂OHCOOH (?=0.19), CO₂ (?=0.12), CH₃COOH (?=0.08), HCHO (?=0.004) and CH₄ (?=0.001). Based on these results a probable reaction mechanism is discussed to explain the rather complicated process.     

Voltammetric and titrimetric study of acid-base properties of some μ-oxo dimeric iron(III) complexes inDMF

Summary The acid-base properties of the -oxo bridged dimeric iron complexes [FeL]₂O with the ligands based on S-alkyl-1,4-bis(substituted salicylidene)isothiosemicarbazide and a tetramer with S-methyl-1,4-bis(salicylidene)isothiosemicarbazide, {[FeL]₂O}₂I₃·I₂, were investigated by cyclic voltammetry at glassy carbon electrode inDMF. Studies were carried out in the presence of either a weak (phenol) or a strong (HClO₄ aq.) acid. The stoichimoetry of the reaction, changes in the general voltammetric pattern and the electrode reaction mechanism were discussed. These studies served as the basis for three-electrode amperometric titrations to determine the content of several of these complexes.

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Voltammetrische und titrimetrische Untersuchung der Säure-Base-Eigenschaften einiger -oxo dimerer Eisen(III)-Komplexe inDMF-Lösungen

Zusammenfassung Die Säure-Base-Eigenschaften einiger dimerer -oxo-Eisen(III)-Komplexe [FeL]₂O mit Liganden auf Basis von 1,4-bis(substituierten Salicyliden)S-(alkyl)isothiosemicarbaziden sowie eines tetrameren Komplexes mit 1,4-Bis(salicyliden)S-methylisothiosemicarbazid, {[FeL]₂O}₂I₃·I₂, wurden mittels zyklischer Voltammetrie an der Glaskohlenstoffelektrode inDMF-Lösungen untersucht. Die Messungen wurden in Gegenwart entweder einer schwachen (Phenol) oder einer starken (HClO₄ aq.) Säure ausgeführt. Die Stöchiometrie der Reaktion, die Änderungen der voltammetrischen Kurven und der Elektroden-Reaktionsmechanismus wurden diskutiert. Diese Untersuchungen stellten eine Basis für Drei-Elektroden amperometrische Titrationen dar, die für die Bestimmung des Gehalts einiger dieser Komplexe angewendet wurden.

     

BODIPY-based hydroxyaryl derivatives as fluorescent pH probes

[structures: see text] Seven new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes with phenolic or naphtholic subunits on position 8 and with substituents having different electron driving forces on positions 3 and 5 were synthesized. Their absorption and steady-state fluorescence properties were investigated as a function of solvent. The novel compounds, with the exception of 4,4-difluoro-8-(4-hydroxyphenyl)-3,5-bis-(4-methoxyphenyl)-4-bora-3a,4a-diaza-s-indacene, are characterized by absorption maxima in the range 493-515 nm and small (400-600 cm(-1)) Stokes shifts. The exceptional dye has absorption maxima in the 570-580 nm region and fluorescence emission maxima around 610-620 nm, depending on the solvent. In aqueous solution, the dyes show a large fluorescent enhancement upon increasing the acidity of the solution. They can be used in aqueous solution as fluorescent pH probes excitable with visible light, with pKa values ranging from 7.5 to 9.3, depending on the substitution pattern on positions 3, 5, and 8.     

Modulation of lysozyme charge influences interaction with phospholipid vesicles

Lysozyme is a globular protein which is known to bind to negatively charged phospholipid vesicles. In order to study the relationship between charge state of the protein and its interaction with negatively charged phospholipid membranes chemical modifications of the proteins were carried out. Succinylation and carbodiimide modification was used to shift the isoelectric point of lysozyme to lower and higher pH values, respectively. The binding of the modified lysozyme to phospholipid vesicles prepared from phosphatidic acid (PA) was determined using microelectrophoresis and ultracentrifugation. At acidic pH of the solution all lysozyme species reduced the surface charges of PA vesicles. Succinylated lysozyme (succ lysozyme) reduced the electrophoretic mobility (EPM) to nearly zero, whereas native lysozyme and carboxylated lysozyme (carbo lysozyme) changed the surface charge to positive values. At neutral pH, the reduction of surface charges was less for carbo lysozyme and unmodified lysozyme. Succ lysozyme did not change the EPM. Unmodified and carbo lysozyme decreased the magnitude of EPM, but the whole complex was still negatively charged. The bound fraction of all modified lysozyme to PA vesicles at high lysozyme/PA ratios was nearly constant at acidic pH. At low lysozyme/PA ratios the extent of bound lysozyme is changed in the order carbo>unmodified>succ lysozyme. Increasing the pH, the extent of bound lysozyme to PA large unilamellar vesicles (LUV) is reduced, at pH 9.0 only 35% of carbo lysozyme, 23% of unmodified lysozyme is bound, whereas succ lysozyme does not bind at pH 7.4 and 9.0. At low pH, addition of all lysozyme species resulted in a massive aggregation of PA liposomes, at neutral pH aggregation occurs at much higher lysozyme/PA ratios. Lysozyme binding to PA vesicles is accompanied by the penetration of lysozyme into the phospholipid membrane as measured by monolayer techniques. The penetration of lysozyme into the monolayer was modulated by pH and ionic strengths. The interaction of lysozyme with negatively charged vesicles leads to a decrease of the phospholipid vesicle surface hydration as measured by the shift of the maximum of the fluorescence signal of a headgroup labeled phospholipid. The binding of bis-ANS as an additional indicator for the change of surface hydrophobicity is increased at low pH after addition of lysozyme to the vesicles. More hydrophobic patches of the lysozyme-PA complex are exposed at low pH. At low pH the binding process of lysozyme to PA vesicles is followed by an extensive intermixing of phospholipids between the aggregated vesicles, accompanied by a massive leakage of the vesicle aqueous content. The extent of lysozyme interaction with PA LUV at neutral and acidic pH is in the order carbo lysozyme>lysozyme>succ lysozyme.     

Diastereoselective reaction of (MP)-pentahelicene-7,8-dione with trans-cyclohexane-1,2-diamine. Thermal and photochemical transformations of its product

The reaction of the title compounds and the transformations of the product, 3 were investigated with an emphasis on the stereochemistry. The primary interaction of the title compounds is feebly stereoselective. The diastereoisomers of product 3 exhibit free energies differing by ca. 16 kJ/mol; diastereoisomerization by helix inversion takes place during the reaction. The most stable diastereoisomers of the intermediate 8 and the product 3 show opposite helicities, which allows isolation of the product 3 in diastereoisomeric ratios from 19:81 to >99:1 depending on solvent and temperature. The free energies of activation for helix inversions of 3 were determined by time-dependent ¹H NMR. The predicted configuration of the more stable diastereoisomer of 3 was confirmed by chemical correlation to be (M,R,R). The four stereoisomers of 3 were separated by analytical enantioselective HPLC and characterized by on-line circular dichroism. Irradiation of 3 afforded the 2-substituted benzimidazole derivative 9.     

Analytical Techniques for Phytocannabinoid Profiling of Cannabis and Cannabis-Based Products—A Comprehensive Review

Cannabis is gaining increasing attention due to the high pharmacological potential and updated legislation authorizing multiple uses. The development of time- and cost-efficient analytical methods is of crucial importance for phytocannabinoid profiling. This review aims to capture the versatility of analytical methods for phytocannabinoid profiling of cannabis and cannabis-based products in the past four decades (1980–2021). The thorough overview of more than 220 scientific papers reporting different analytical techniques for phytocannabinoid profiling points out their respective advantages and drawbacks in terms of their complexity, duration, selectivity, sensitivity and robustness for their specific application, along with the most widely used sample preparation strategies. In particular, chromatographic and spectroscopic methods, are presented and discussed. Acquired knowledge of phytocannabinoid profile became extremely relevant and further enhanced chemotaxonomic classification, cultivation set-ups examination, association of medical and adverse health effects with potency and/or interplay of certain phytocannabinoids and other active constituents, quality control (QC), and stability studies, as well as development and harmonization of global quality standards. Further improvement in phytocannabinoid profiling should be focused on untargeted analysis using orthogonal analytical methods, which, joined with cheminformatics approaches for compound identification and MSLs, would lead to the identification of a multitude of new phytocannabinoids.     

Exponential-trigonometric basis functions in the coulomb four-body problem

Basis functions of a new type—specifically, exponential-trigonometric functions depending on all six interparticle distances—have been proposed for the Coulomb four-body problem. A method has been developed for computing nine-dimensional integrals determining the matrix elements of the Hamiltonian for a four-body system and featuring these functions. The efficiency of the approach that relies on the proposed basis functions has been tested by calculating the e ⁺ e ^? e ⁺ e ^?, p ⁺μ^? p ⁺μ^?, μ⁺ e ^?μ⁺ e ^?, and p ⁺ e ^? p ⁺ e ^? molecules.