Electrochemical Sensing of Pb2+ and Cd2+ Ions with the Use of Electrode Modified with Carbon-Covered Halloysite and Carbon Nanotubes

A novel voltammetric method for the sensitive and selective determination of cadmium and lead ions using screen-printed carbon electrodes (SPCEs) modified with carbon-deposited natural halloysite (C_Hal) and multi-walled carbon nanotubes (MWCNTs) was developed. The electrochemical properties of the proposed sensor were investigated by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV), while the morphology and structure were established by scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). A two-factorial central composite design (CCD) was employed to select the composition of the nanocomposite modifying the electrode surface. The optimal measuring parameters of differential pulse anodic stripping voltammetry (DPASV) used for quantitative analysis were established with the Nelder–Mead simplex method. In the analytical investigation of Cd(II) and Pb(II) ions by DPASV, the MWCNTs/C_Hal/Nafion/SPCE exhibited a linear response in the concentration range of 0.1–10.0 µmol L⁻¹ (for both ions) with a detection limit of 0.0051 and 0.0106 µmol L⁻¹ for Pb(II) and Cd(II), respectively. The proposed sensor was successfully applied for the determination of metal ions in different natural water and honey samples with recovery values of 96.4–101.6%.     

Cebranopadol as a Novel Promising Agent for the Treatment of Pain

Opioids are used to treat pain, but despite their effectiveness, they possess several side effects such as respiratory depression, tolerance and physical dependence. Cebranopadol has been evaluated as a solution to this problem. The compound acts on the mu opioid receptor and the nociceptin/orphanin receptor and these receptors co-activation can reduce opioid side-effects without compromising analgesia. In the present review, we have compiled information on the effects of cebranopadol, its pharmacokinetics, and clinical trials involving cebranopadol, to further explore its promise in pain management.     

Optimization of Bifunctional Antisense Oligonucleotides for Regulation of Mutually Exclusive Alternative Splicing of PKM Gene

Oligonucleotide tools, as modulators of alternative splicing, have been extensively studied, giving a rise to new therapeutic approaches. In this article, we report detailed research on the optimization of bifunctional antisense oligonucleotides (BASOs), which are targeted towards interactions with hnRNP A1 protein. We performed a binding screening assay, Kd determination, and UV melting experiments to select sequences that can be used as a high potency binding platform for hnRNP A1. Newly designed BASOs were applied to regulate the mutually exclusive alternative splicing of the PKM gene. Our studies demonstrate that at least three repetitions of regulatory sequence are necessary to increase expression of the PKM1 isoform. On the other hand, PKM2 expression can be inhibited by a lower number of regulatory sequences. Importantly, a novel branched type of BASOs was developed, which significantly increased the efficiency of splicing modulation. Herein, we provide new insights into BASOs design and show, for the first time, the possibility to regulate mutually exclusive alternative splicing via BASOs.     

Effect of Cordyceps spp. and Cordycepin on Functions of Bones and Teeth and Related Processes: A Review

Cordyceps spp. (belonging to the Ascomycota group) are entomopathogenic mushrooms that have traditionally been used in ethnomedicine in Asian countries such as China, Japan, Korea, and India. They are unique parasites of larvae of selected species of moths. Cordyceps militaris is one of the best sources of cordycepin. Worldwide, osteoporosis is one of the most common bone diseases, whose pharmacotherapy includes various medical interventions; however, the research and development of new molecules and new drugs is required. The impact of adenosine receptors (ARs) on the purinergic signaling pathway may regulate proliferation, differentiate dental pulp stem cells and bone marrow, and modulate osteogenesis and bone repair. The aim of the review was to collect and analyze the available data on the effects of Cordyceps spp. or cordycepin on bone function and related processes. To the best of our knowledge, this is the first systematic review in this perspective, not necessarily using mushroom raw material or even the isolated parent compound cordycepin, but new molecules that are analogs of nucleosides, such as those from C. militaris. This review found that Cordyceps spp. or isolated cordycepin interacts via the AR, 5′ adenosine monophosphate-activated protein kinase (AMPK), and adenosine-5′-triphosphate (ATP) signaling pathway and evaluated their impact on bones, teeth, and dental pulp. Cordyceps spp. was found to have the potential to develop regenerative medicines, thus providing an opportunity to expand the treatment or intervention methods in the recovery after traumatic injuries, convalescence, and terminal-stage or devastating diseases.     

Synthesis and Crystal Structure of Adamantylated 4,5,6,7-Tetrahalogeno-1H-benzimidazoles Novel Multi-Target Ligands (Potential CK2, M2 and SARS-CoV-2 Inhibitors); X-ray/DFT/QTAIM/Hirshfeld Surfaces/Molecular Docking Study

A series of new congeners, 1-[2-(1-adamantyl)ethyl]-1H-benzimidazole (AB) and 1-[2-(1-adamantyl)ethyl]-4,5,6,7-tetrahalogeno-1H-benzimidazole (Hal=Cl, Br, I; tClAB, tBrAB, tIAB), have been synthesized and studied. These novel multi-target ligands combine a benzimidazole ring known to show antitumor activity and an adamantyl moiety showing anti-influenza activity. Their crystal structures were determined by X-ray, while intermolecular interactions were studied using topological Bader’s Quantum Theory of Atoms in Molecules, Hirshfeld Surfaces, CLP and PIXEL approaches. The newly synthesized compounds crystallize within two different space groups, P-1 (AB and tIAB) and P2₁/c (tClAB and tBrAB). A number of intramolecular hydrogen bonds, C−H⋯Hal (Hal=Cl, Br, I), were found in all halogen-containing congeners studied, but the intermolecular C−H⋯N hydrogen bond was detected only in AB and tIAB, while C−Hal⋯π only in tClAB and tBrAB. The interplay between C−H⋯N and C−H⋯Hal hydrogen bonds and a shift from the strong (C−H⋯Cl) to the very weak (C−H⋯I) attractive interactions upon Hal exchange, supplemented with Hal⋯Hal overlapping, determines the differences in the symmetry of crystalline packing and is crucial from the biological point of view. The hypothesis about the potential dual inhibitor role of the newly synthesized congeners was verified using molecular docking and the congeners were found to be pharmaceutically attractive as Human Casein Kinase 2, CK2, inhibitors, Membrane Matrix 2 Protein, M2, blockers and Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV-2, inhibitors. The addition of adamantyl moiety seems to broaden and modify the therapeutic indices of the 4,5,6,7-tetrahalogeno-1H-benzimidazoles.     

Review: Chemistry of the phosphinophosphinidene tBu2P?P,a novel π‐electron ligand

In reactions with transition metal compounds, ^tBu₂P? P?P(X)^tBu₂ (X = Br, Me) acts mainly as a precursor of the ^tBu₂P? P ligand, whereas ^tBu(Me₃Si)P? P?P(Me)^tBu₂ acts as a precursor of the (Me₃Si)P?P^tBu ligand. Up to now, only Pt(0) d¹⁰ ML₂ metal centres were found to be able to stabilize the ^tBu₂P? P group in ‘pure form’ by means of η²‐coordination (side on). Several compounds of the [{η² ? ^tBu₂P? P}Pt(PR₃)₂] type were sufficiently stable to be isolated and characterized; however, not all of them gave single crystals suitable for X‐ray structure determinations. The X‐ray structures of these compounds and of [{µ ? (1,2:2 ? η ? ^tBu₂P? P)Pt(PR₃)₂} {M(CO)₅}] strongly suggest the ethene‐like form of 1,1‐di‐tert‐butyldiphosphene in these complexes. Such a form is also in agreement with RI DFT calculations with SVP basis for free ^tBu₂P? P. However, in trapping experiments with cyclic olefins and cyclic dienes ^tBu₂P? P exhibits, to some extent, electrophilic ‘singlet carbene’ properties. Copyright © 2002 John Wiley & Sons, Ltd.     

Effect of Impregnation Conditions on the Structure and Chromatographic Behavior of TLC Adsorbents Modified with Cu(II) and Ni(II) Salts

JPC – Journal of Planar Chromatography – Modern TLC - Attempts have been made to find the optimum conditions for modification of silica gel and amino- and cyanopropyl-bonded silica with...     

Highly efficient magnesium initiators for lactide polymerization

Two monomeric, six-coordinated magnesium complexes with bulky aminophenolate ligands [(Htbpoa)2Mg] (1) and [(Htbpca)2Mg(THF)2] (2), where Htbpoa =N-[methyl(2-hydroxy-3,5-di-tert-butylphenyl)]-N-methyl-N-methyl-1,3-dioxolaneamine and Htbpca =N-[methyl(2-hydroxy-3,5-di-tert-butylphenyl)]-N-methyl-N-cyclohexylamine have been prepared, characterized and employed as initiators for lactide polymerization. The crystal structure of the homoleptic compound 1 has been determined and shows that the six-coordinate magnesium atom in 1 is surrounded by two tridendate tbpoa ligands. In the solution, however, complex 1 exists in equilibrium with a five-coordinate species 1a having one oxolane fragment dangling. The tbpoa and tbpca ligands in 1 and 2 play a dual role, as the ancillary ligand stabilizing the monomeric magnesium species and as the initiating polymerization group.     

Infrared,Raman, and cndo studies of the effect of ions on the electron density distribution in formamide

Infrared and Raman spectra of electrolyte solutions in formamide have been investigated for amide I and CH stretching regions. The effects of the cation-molecule and anion-molecule interactions on the frequency shift and IR intensity are discussed in terms of CNDO/2 calculations performed for the model formamide complexes with Li⁺ and F^? ions. It is suggested that the considerable CH frequency shift upon cornplexing with cation is due to the trans lone pair effect.     

Influence of heavy metals, especially lead, on lipid metabolism, serum alpha-tocopherol level, total antioxidant status, and erythrocyte redox status of copper smelter workers

An assessment of influence of the occupational exposure to heavy metals, especially lead, on serum lipids (including lipid peroxides), total antioxidant status, erythrocyte redox status, and serum alpha-tocopherol level was performed in a group of 141 healthy male copper smelter workers. The following parameters were measured: blood lead and cadmium levels, serum manganese, copper, zinc, calcium and magnesium levels, free erythrocyte protoporphyrins (FEP), total cholesterol, HDL₂-, HDL₃-cholesterol, triglycerides and lipid peroxides in serum, erythrocyte superoxide dismutase (SOD_E), catalase (Cat_E) and glutathion peroxidase (PxGSH_E) activities, erythrocyte reduced glutathione level (GSH_E), serum alpha-tocopherol level, and serum total antioxidant status (TAS). Mean Pb_B was within the norm range (328.2 ± 141.7 μg/L), but mean Mn_S concentration slightly exceeded 10 μg/L (11.04 ± 3.79 μg/L). Mean cholesterol and triglycerides concentrations were near the highest borderline values. We found a significantly negative correlation between lead levels and HDL₃-cholesterol (r = 0.253, P < 0.05). Erythocyte catalase activity and TAS were lowered. TAS showed significant negative correlation with Pb_B. A group of workers with Pb_B≥ 400 μg/L had significantly lower Cat_E, lower TAS, and lower HDL₃-cholesterol, compared to the workers with Pb < 400 μg/L. We have also found positive correlation between alpha-tocopherol and total cholesterol (r = 0.267, P < 0.05) and between alpha-tocopherol and LDL-cholesterol (r = 0.207, P < 0.05).