Theoretical study of cobalt and nickel complexes involved in methyl transfer reactions: structures,redox potentials and methyl binding energies

Structural Chemistry - Cobalamins, cobalt glyoximate complexes and nickel complexes with Triphos (bis(diphenylphosphinoethyl)phenylphosphine) and PPh2CH2CH2SEt ligands were studied with the...     

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-β-cyclodextrin, Pluronic^® F-127, and Soluplus^®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the “halo effect” on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic^® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10⁻⁶ cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-β-cyclodextrin, Pluronic^® F-127, and Soluplus^®), although in their cases, the values of apparent constants permeability were decreased.     

Diketopiperazine-Based,Flexible Tadalafil Analogues: Synthesis,Crystal Structures and Biological Activity Profile

Phosphodiesterase 5 (PDE5) is one of the most extensively studied phosphodiesterases that is highly specific for cyclic-GMP hydrolysis. PDE5 became a target for drug development based on its efficacy for treatment of erectile dysfunction. In the present study, we synthesized four novel analogues of the phosphodiesterase type 5 (PDE5) inhibitor—tadalafil, which differs in (i) ligand flexibility (rigid structure of tadalafil vs. conformational flexibility of newly synthesized compounds), (ii) stereochemistry associated with applied amino acid building blocks, and (iii) substitution with bromine atom in the piperonyl moiety. For both the intermediate and final compounds as well as for the parent molecule, we have established the crystal structures and performed a detailed analysis of their structural features. The initial screening of the cytotoxic effect on 16 different human cancer and non-cancer derived cell lines revealed that in most cases, the parent compound exhibited a stronger cytotoxic effect than new derivatives, except for two cell lines: HEK 293T (derived from a normal embryonic kidney, that expresses a mutant version of SV40 large T antigen) and MCF7 (breast adenocarcinoma). Two independent studies on the inhibition of PDE5 activity, based on both pure enzyme assay and modulation of the release of nitric oxide from platelets under the influence of tadalafil and its analogues revealed that, unlike a reference compound that showed strong PDE5 inhibitory activity, the newly obtained compounds did not have a noticeable effect on PDE5 activity in the range of concentrations tested. Finally, we performed an investigation of the toxicological effect of synthesized compounds on Caenorhabditis elegans in the highest applied concentration of 6a,b and 7a,b (160 μM) and did not find any effect that would suggest disturbance to the life cycle of Caenorhabditis elegans. The lack of toxicity observed in Caenorhabditis elegans and enhanced, strengthened selectivity and activity toward the MCF7 cell line made 7a,b good leading structures for further structure activity optimization and makes 7a,b a reasonable starting point for the search of new, selective cytotoxic agents.     

Vibrational Circular Dichroism Unravels Supramolecular Chirality and Hydration Polymorphism of Nucleoside Crystals

Vibrational circular dichroism (VCD) spectroscopy has been widely used to study (bio)molecules in solution. However, its solid-state applications have been restricted due to experimental limitations and artifacts. Having overcome some of them, the first VCD study of nucleoside crystals is now presented. A two-orders-of-magnitude enhancement of VCD signal was observed due to high molecular order in the crystals and resulting supramolecular chirality. This allowed to obtain high-quality VCD spectra within minutes using minute amounts of samples. The VCD technique is extremely sensitive in detecting changes in a crystal order and is able to distinguish different hydration states of crystals. This elevates it to a new level, as a fast and efficient tool to study chiral crystalline samples. This study demonstrates that VCD is capable of near-instantaneous detection of hydration polymorphs and crystal degradation, which is of substantial interest in pharmaceutical industry (quality and stability control).     

Functionalization of vinyl-substituted linear oligo- and polysiloxanes via ruthenium catalyzed silylative coupling with styrene

Efficient silylative coupling of linear vinyl-substituted oligo- and polysiloxanes with styrene in the presence of [RuHCl(CO)(PPh₃)₃] (1) and particularly [RuHCl(CO)(PCy₃)₂] (2) combined with copper(I) chloride is described. Treatment of styrene, with terminal or side vinyl group at siloxane skeleton catalyzed by [RuHCl(CO)(PCy₃)₂]/CuCl results in the quantitative and selective formation of respective silylative coupling products.     

Chemical Transformation of Humic Acid Molecules under the Influence of Mineral,Fungal and Bacterial Fertilization in the Context of the Agricultural Use of Degraded Soils

The main goal of this work was to study the structural transformation of humic acids (HAs) under the influence of selected strains of fungi (Aspergillus niger and Paecilomyces lilacinus) and bacteria (Bacillus sp., Paenibacillus polymyxa and Bacillus amyloliquefaciens) with/without the presence of NPK fertilizers. Two-year experiments were conducted on two different soils and HAs isolated from these soils were examined for structure, humification degree, and quantity using fluorescence and UV-Vis spectroscopy, elemental analysis, and extraction methods. Results showed that the applied additives contributed to the beneficial transformation of HAs, but effects differed for various soils. HAs from silty soil with higher organic carbon content showed simplification of their structure, and decreases in humification, molecular weight, and aromaticity under the influence of fungi and bacteria without NPK, and with NPK alone. With both fungi and NPK, increases in O/H and O/C atomic ratios indicated an increase in the number of O-containing functional groups. HAs from sandy soil did not show as many significant changes as did those from silty soil. Sandy soil exhibited a strong decline in HA content in the second year that was reduced/neutralized by the presence of fungi, bacteria, and NPK. Periodically observed fluorescence at ~300 nm/450 nm reflected formation of low-molecular HAs originating from the activity of microorganisms.     

Solvent‐Driven Conformational Exchange for Amide‐Linked Bichromophoric BODIPY Derivatives

The fluorescence lifetime and quantum yield are seen to depend in an unexpected manner on the nature of the solvent for a pair of tripartite molecules composed of two identical boron dipyrromethene (BODIPY) residues attached to a 1,10‐phenanthroline core. A key feature of these molecular architectures concerns the presence of an amide linkage that connects the BODIPY dye to the heterocyclic platform. The secondary amide derivative is more sensitive to environmental change than is the corresponding tertiary amide. In general, increasing solvent polarity, as measured by the static dielectric constant, above a critical threshold tends to reduce fluorescence but certain hydrogen bond accepting solvents exhibit anomolous behaviour. Fluorescence quenching is believed to arise from light‐induced charge transfer between the two BODIPY dyes, but thermodynamic arguments alone do not explain the experimental findings. Molecular modelling is used to argue that the conformation changes in strongly polar media in such a way as to facilitate improved rates of light‐induced charge transfer. These solvent‐induced changes, however, differ remarkably for the two types of amide.     

Explosive hazards in polyaniline chemistry

Polyaniline, a conducting polymer, is prepared by the oxidation of aniline with various oxidants. When using ammonium peroxydisulfate or hydrogen peroxide at high concentrations, the temperature may exceed boiling point of reaction mixture, which then explodes. This represents a safety hazard in the synthesis of polyaniline. Also polyaniline samples prepared in the solutions of nitric acid may spontaneously ignite or decompose during the characterization. The synthesis using the recommended protocol is safe.     

Application of dispersive liquid–liquid microextraction and gas chromatography with mass spectrometry for the determination of oxygenated volatile organic compounds in effluents from the production of petroleum bitumen

We present a new procedure for the determination of oxygenated volatile organic compounds in samples of postoxidative effluents from the production of petroleum bitumens using dispersive liquid–liquid microextraction and gas chromatography with mass spectrometry. The eight extraction parameters were optimized for 43 oxygenated volatile organic compounds. The detection limits obtained ranged from 0.07 to 0.82 μg/mL for most of the analytes, the precision was good (relative standard deviation below 2.91% at the 5 μg/mL level and 4.75% at the limit of quantification), the recoveries for the majority of compounds varied from 70.6 to 118.9%, and the linear range was wide, which demonstrates the usefulness of the procedure. The developed procedure was used for the determination of oxygenated volatile organic compounds in samples of raw postoxidative effluents and in effluents after chemical treatment. In total, 23 compounds at concentration levels from 0.37 to 32.95 μg/mL were identified in real samples. The same samples were also analyzed in the SCAN mode, which resulted in four more phenol derivatives being identified and tentatively determined. The studies demonstrated the need for monitoring volatile organic compounds content in effluents following various treatments due to the formation of secondary oxygenated volatile organic compounds.     

New procedure for the control of the treatment of industrial effluents to remove volatile organosulfur compounds

We present a new procedure for the determination of volatile organosulfur compounds in samples of industrial effluents using dispersive liquid–liquid microextraction and gas chromatography with flame photometric detection. Initially, the extraction parameters were optimized. These included: type and volume of extraction solvent, volume of disperser solvent, salting out effect, pH, time and speed of centrifugation as well as extraction time. The procedure was validated for 30 compounds. The developed procedure has low detection limits of 0.0071–0.49 μg/L and a good precision (relative standard deviation values of 1.2–5.0 and 0.6–4.1% at concentrations of 1 and 10 μg/L, respectively). The procedure was used to determine the content of volatile organosulfur compounds in samples of effluents from the production of bitumens before and after chemical treatment, in which six compounds were identified, including 2‐mercaptoethanol, thiophenol, thioanisole, dipropyl disulfide, 1‐decanethiol, and phenyl isothiocyanate at concentrations ranging from 0.47 to 8.89 μg/L. Problems in the determination of organosulfur compounds related to considerable changes in composition of the effluents, increase in concentration of individual compounds and appearance of secondary pollutants during effluent treatment processes are also discussed.