Hydrogenation of 2-Butyn-1,4-diol in the Presence of Functional Crosslinked Resin Supported Pd Catalyst. The Role of Polymer Properties in Activity/Selectivity Pattern

Functional gel type resins of various crosslinking degrees (3–20%) with C=O and carboxylic groups were used as the supports for Pd catalysts (0.5–2 wt% Pd). The role of polymer properties was studied in the hydrogenation of 2-Butyne-1,4-diol (B3-D) to alkene (B2-D) and alkane (B1-D). Hydrogenation was studied at atmospheric pressure of hydrogen using THF, H₂O and THF + H₂O mixtures as the solvents. Systematic studies were carried out to determine the role of the type of solvent, crosslinking degree of polymer, the content of Pd in catalysts, initial B3-D concentration and the procedure of catalyst reduction in activity/selectivity behaviour of catalysts. Swelling degree of polymer matrix under the catalytic run exhibits crucial role in the activity and selectivity to alkene, B2-D. In the presence of highly expanded catalyst (THF solvent, 3% crosslinking degree, 1 wt% Pd) the alkyne, B3-D, is hydrogenated to alkene, B2-D, with selectivity ca. 85% up to high B3-D conversion (90%). The suppression of alkene to alkane hydrogenation in the stage of B3-D is ascribed to high ability of Pd centres in the Pd/OFP catalysts to strong adsorption of alkyne substrate. It may also be related to steric hindrances of polymer in the vicinity of active Pd centres. At small content of added water (5% by vol.) to THF the catalysts offer very attractive performance in terms of activity and 98% selectivity to alkene. Water facilitates interactions of B3-D with functional groups of polymer that leads to better expansion of polymer matrix and more effective suppression of alkene hydrogenation in the alkyne stage.     

Synthesis of glycidyl esters

A novel method of synthesis of glycidyl carboxylates (2,3‐epoxypropyl carboxylates, RCOOCH₂CH‐CH₂O) has been developed by carrying out the reaction of epichlorhydrin with a carboxylic acid in the presence of chromium acetate catalyst and subsequent dehydrochlorination of the resulting mixture of chlorohydrin esters followed by their separation. © 1999 Society of Chemical Industry     

Viscosity effects in the photopolymerization of two‐monomer systems

Photopolymerization kinetics and viscosity behavior of five different two‐monomer systems forming hydrogen bonds and composed of mixtures of a high viscosity monomer (HVM) and a low viscosity monomer (LVM) at various molar ratios were investigated at six polymerization temperatures. The monomers used were mono‐ or dimethacrylates. Detailed viscosity measurements of the monomer mixtures showed significant negative deviations from the theoretical values (characterized by excess logarithm viscosities) indicating that interactions between the molecules of the same type (in individual monomers) are stronger than those between two molecules of different types (HVM and LVM). The photopolymerization kinetics were analyzed from the point of view of the appearance, viscosity and temperature behavior of the most reactive composition (MRC), the one showing the highest value of the maximum polymerization rate within a range of the HVM: LVM ratios. It was found that MRC appearance is determined mainly by the initial viscosity of the two‐monomer system, whereas the functionality of the monomers (and network formation) is much less important (MRC is observed even in linear systems). The initial viscosity of all the monomer mixtures showing MRC lay in the range of 0.06–2 Pa s, which is narrow compared to the range of viscosities of the monomers (approximately 10^?3–10³ Pa s). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Anticorrosive effectiveness of coatings with reduced content of Zn pigments in comparison with zinc-rich primers

ABSTRACT

Typically, an anticorrosive coating system for long-term protection consists of a primer, one or several intermediate coats, and a topcoat. In such systems, zinc-rich primers are often used as they ensure good adhesion to the substrate and protect it from corrosion. Such coatings are very highly pigmented, which sometimes leads to losses in cohesive strength and deterioration of mechanical properties. Furthermore, Zn is known to be harmful to the environment. In this work we present Zn primers with reduced Zn content and better protective properties than traditional zinc-rich primers. The formulations of different Zn pigments in the epoxy matrix were developed with the concentration of zinc particles reduced to about 50% in the dry coating. To evaluate the distribution of pigments scanning electron microscopy has been employed. The anticorrosive properties were tested using the salt spray test and electrochemical impedance spectroscopy. The mechanical properties of the coatings were also tested.     

Fabrication of nanoporous TiO2 by electrochemical anodization

The formation of self-organized porous titania is achieved by electrochemical anodization under a potentiostatic regime. Anodic titanium oxide (ATO) was fabricated by a three-step self-organized anodization of the Ti foil in an ethylene glycol electrolyte containing 0.38 wt% of NH₄F and 1.79 wt% of H₂O. Anodizing was carried out at the constant cell potential ranging from 30 to 70 V at the temperature of 20 °C. It was found that nanoporous TiO₂ arrays can be obtain only after a short duration of the third step (10 min). The influence of anodizing potential on the structural parameters of porous anodic titania including pore diameter, interpore distance, wall thickness, porosity and pore density was extensively studied. The linear dependencies between interpore distance, pore diameter and wall thickness upon the anodizing potential were found. The regularity of pore arrangement was monitored qualitatively by fast Fourier transforms (FFTs) of top-view FE-SEM images. It was found that the best arrangement of nanopores is observed at 40 V. This finding was confirmed by the analysis of pore circularity. The highest circularity of pores was observed once again at 40 V.     

Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes its dimerization and the activation of the intracellular signaling cascade. Signal transduction involves the activation of MAPK, AKT, and JNK, resulting in DNA synthesis and cell proliferation. In cancer cells, binding the ligand to the EGFR also leads to its dimerization and transduction of the signal to the cell interior. It has been demonstrated that activating mutations in the gene for EGFR-exon19 (deletion), L858R point mutation in exon 21, and mutation in exon 20 results in cancer cell proliferation. Continuous stimulation of the receptor inhibits apoptosis, stimulates invasion, intensifies angiogenesis, and facilitates the formation of distant metastases. As a consequence, the cancer progresses. These activating gene mutations for the EGFR are present in 10–20% of lung adenocarcinomas. Approximately 3–7% of patients with lung adenocarcinoma have the echinoderm microtubule-associated protein-like 4 (EML4)/ALK fusion gene. The fusion of the two genes EML4 and ALK results in a fusion gene that activates the intracellular signaling pathway, stimulates the proliferation of tumor cells, and inhibits apoptosis. A new group of drugs—small-molecule tyrosine kinase inhibitors—has been developed; the first generation includes gefitinib and erlotinib and the ALK inhibitor crizotinib. These drugs reversibly block the EGFR by stopping the signal transmission to the cell. The second-generation tyrosine kinase inhibitor (TKI) afatinib or ALK inhibitor alectinib block the receptor irreversibly. Clinical trials with TKI in patients with non-small cell lung adenocarcinoma with central nervous system (CNS) metastases have shown prolonged, progression-free survival, a high percentage of objective responses, and improved quality of life. Resistance to treatment with this group of drugs emerging during TKI therapy is the basis for the detection of resistance mutations. The T790M mutation, present in exon 20 of the EGFR gene, is detected in patients treated with first- and second-generation TKI and is overcome by Osimertinib, a third-generation TKI. The I117N resistance mutation in patients with the ALK mutation treated with alectinib is overcome by ceritinib. In this way, sequential therapy ensures the continuity of treatment. In patients with CNS metastases, attempts are made to simultaneously administer radiation therapy and tyrosine kinase inhibitors. Patients with lung adenocarcinoma with CNS metastases, without activating EGFR mutation and without ALK rearrangement, benefit from immunotherapy. This therapeutic option blocks the PD-1 receptor on the surface of T or B lymphocytes or PD-L1 located on cancer cells with an applicable antibody. Based on clinical trials, pembrolizumab and all antibodies are included in the treatment of non-small cell lung carcinoma with CNS metastases.     

Sirtuins as Important Factors in Pathological States and the Role of Their Molecular Activity Modulators

Sirtuins (SIRTs), enzymes from the family of NAD⁺-dependent histone deacetylases, play an important role in the functioning of the body at the cellular level and participate in many biochemical processes. The multi-directionality of SIRTs encourages scientists to undertake research aimed at understanding the mechanisms of their action and the influence that SIRTs have on the organism. At the same time, new substances are constantly being sought that can modulate the action of SIRTs. Extensive research on the expression of SIRTs in various pathological conditions suggests that regulation of their activity may have positive results in supporting the treatment of certain metabolic, neurodegenerative or cancer diseases or this connected with oxidative stress. Due to such a wide spectrum of activity, SIRTs may also be a prognostic markers of selected pathological conditions and prove helpful in assessing their progression, especially by modulating their activity. The article presents and discusses the activating or inhibiting impact of individual SIRTs modulators. The review also gathered selected currently available information on the expression of SIRTs in individual disease cases as well as the biological role that SIRTs play in the human organism, also in connection with oxidative stress condition, taking into account the progress of knowledge about SIRTs over the years, with particular reference to the latest research results.     

The Involvement of Xanthone and (E)-Cinnamoyl Chromophores for the Design and Synthesis of Novel Sunscreening Agents

Excessive UV exposure contributes to several pathological conditions like skin burns, erythema, premature skin aging, photodermatoses, immunosuppression, and skin carcinogenesis. Effective protection from UV radiation may be achieved with the use of sunscreens containing UV filters. Currently used UV filters are characterized by some limitations including systemic absorption, endocrine disruption, skin allergy induction, and cytotoxicity. In the research centers all over the world new molecules are developed to improve the safety, photostability, solubility, and absorption profile of new derivatives. In our study, we designed and synthesized seventeen novel molecules by combining in the structures two chromophores: xanthone and (E)-cinnamoyl moiety. The ultraviolet spectroscopic properties of the tested compounds were confirmed in chloroform solutions. They acted as UVB or UVA/UVB absorbers. The most promising compound 9 (6-methoxy-9-oxo-9H-xanthen-2-yl)methyl (E)-3-(2,4-dimethoxyphenyl)acrylate) absorbed UV radiation in the range 290–369 nm. Its photoprotective activity and functional photostability were further evaluated after wet milling and incorporation in the cream base. This tested formulation with compound 9 possessed very beneficial UV protection parameters (SPF_{in vitro} of 19.69 ± 0.46 and UVA PF of 12.64 ± 0.32) which were similar as broad-spectrum UV filter tris-biphenyl triazine. Additionally, compound 9 was characterized by high values of critical wavelength (381 nm) and UVA/UVB ratio (0.830) thus it was a good candidate for broad-spectrum UV filter and it might protect skin against UVA-induced photoaging. Compound 9 were also shown to be photostable, non-cytotoxic at concentrations up to 50 µM when tested on five cell lines, and non-mutagenic in Ames test. It also possessed no estrogenic activity, according to the results of MCF-7 breast cancer model. Additionally, its favorable lipophilicity (miLogP = 5.62) does not predispose it to penetrate across the skin after topical application.     

The Role of TNF-α and Anti-TNF-α Agents during Preconception,Pregnancy, and Breastfeeding

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.