Unsymmetrically-Substituted 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione Scaffold—A Useful Tool for Bioactive Molecules Design

Unsymmetrically N-substituted and N,N’-disubstituted 5,12-dihydrodibenzo [b,f][1,4]diazocine-6,11-diones were synthesized in the new protocol. The desired modifications of the dibenzodiazocine scaffold were introduced at the stages of proper selection of building blocks as well as post-cyclization modifications with alkylation or acylation agents, expanding the structural diversity and possible applications of synthesized molecules. The extension of developed method resulted in the synthesis of novel: tricyclic 5,10-dihydrobenzo[b]thieno[3,4-f][1,4]diazocine-4,11-dione scaffold and fused pentacyclic framework possessing two benzodiazocine rings within its structure. Additionally, the unprecedented rearrangement of 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-diones to 2-(2-aminophenyl)isoindoline-1,3-diones was observed under the basic conditions in the presence of sodium hydride for secondary dilactams. The structures of nine synthesized products have been established by single-crystal X-ray diffraction analysis. Detailed crystallographic analysis of the investigated tri- and pentacyclic systems has shed more light on their structural features. One cell line derived from non-cancerous cells (EUFA30—human fibroblasts) and three tumor cells (U87—human primary glioblastoma, HeLa—cervix adenocarcinoma, BICR18—laryngeal squamous cell carcinoma) were used to determine the cytotoxic effect of the newly synthesized compounds. Although these compounds showed a relatively weak cytotoxic effect, the framework obtained for 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione could serve as a convenient privilege structure for the design and development of novel bioactive molecules suitable for drug design, development and optimization programs

Wybrane aspekty funkcjonowania Sejmu w latach 1997–2007

Praca recenzowana / peer-reviewed paperPraca naukowa finansowana ze środków na naukę w latach 2006–2008 jako projekt badawczy własny Nr 1 H02E 052 3

The multidirectional auxeticity and negative linear compressibility of a 3D mechanical metamaterial

In this work, through the use of a theoretical model, we analyse the potential of a specific three-dimensional mechanical metamaterial composed of arrowhead-like structural units to exhibit a negative Poisson’s ratio for an arbitrary loading direction. Said analysis allows us to assess its suitability for use in applications where materials must be able to respond in a desired manner to a stimulus applied in multiple directions. As a result of our studies, we show that the analysed system is capable of exhibiting auxetic behaviour for a broad range of loading directions, with isotropic behaviour being shown in some planes. In addition to that, we show that there are also certain loading directions in which the system manifests negative linear compressibility. This enhances its versatility and suitability for a number of applications where materials exhibiting auxetic behaviour or negative linear compressibility are normally implemented.peer-reviewe

The serum concentration of copper in bipolar disorder

Aim. Some scientific reports indicate the changes in the concentration of serum copper in patients with bipolar disorder (BD), however the data are inconclusive. The aim of this study was to assess the concentration of copper in the blood serum of patients in various phases of BD compared to healthy volunteers, taking into consideration the specific clinical features, and the stage of illness. Methods. The study enrolled 133 patients with a diagnosis of BD (type I, II and NOS), including 61 people in depressive episode, 23 in mania or hypomania and 49 in remission. The control group consisted of 50 people. Atomic absorption spectrometry was used to measure the concentration of copper. Results. There were no statistically significant differences in the serum copper concentration between patients in various phases of BD (mania/hypomania, depression, remission), sub-types (Type I, Type II + NOS) or stages and healthy volunteers. However, serum copper concentrations in patients in stage 1 was significantly higher than in advanced stages (2+3+4), (β = 0.22; p = 0.02). Serum copper concentration was also the higher, the later the age of onset was (β = 0.33; p < 0.001), and the lower, the greater the number of illness episodes (β = – 0.23; p = 0.02) (multiple regression model, adj R2 = 0.19, p = 0.0001). Conclusions. The dependencies demonstrated above may reflect pathophysiological processes that occur in the course of BD (e.g., inflammatory response and oxidative stress) with a different intensity depending on its stage

The serum zinc concentration as a potential biological marker in patients with major depressive disorder

Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06 mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06 mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD

Myśl i polityka: księga pamiątkowa dedykowana profesorowi Jackowi Marii Majchrowskiemu T. 3

Publikacja jubileuszowa z okazji 40-lecia pracy naukowej profesora Jacka Majchrowskieg

The Multidirectional Auxeticity and Negative Linear Compressibility of a 3D Mechanical Metamaterial

In this work, through the use of a theoretical model, we analyse the potential of a specific three-dimensional mechanical metamaterial composed of arrowhead-like structural units to exhibit a negative Poisson&rsquo;s ratio for an arbitrary loading direction. Said analysis allows us to assess its suitability for use in applications where materials must be able to respond in a desired manner to a stimulus applied in multiple directions. As a result of our studies, we show that the analysed system is capable of exhibiting auxetic behaviour for a broad range of loading directions, with isotropic behaviour being shown in some planes. In addition to that, we show that there are also certain loading directions in which the system manifests negative linear compressibility. This enhances its versatility and suitability for a number of applications where materials exhibiting auxetic behaviour or negative linear compressibility are normally implemented

Controllable Hierarchical Mechanical Metamaterials Guided by the Hinge Design

In this work, we use computer simulations (Molecular Dynamics) to analyse the behaviour of a specific auxetic hierarchical mechanical metamaterial composed of square-like elements. We show that, depending on the design of hinges connecting structural elements, the system can exhibit a controllable behaviour where different hierarchical levels can deform to the desired extent. We also show that the use of different hinges within the same structure can enhance the control over its deformation and mechanical properties, whose results can be applied to other mechanical metamaterials. In addition, we analyse the effect of the size of the system as well as the variation in the stiffness of its hinges on the range of the exhibited auxetic behaviour (negative Poisson’s ratio). Finally, it is discussed that the concept presented in this work can be used amongst others in the design of highly efficient protective devices capable of adjusting their response to a specific application