Special Issue 2024

Table of contents

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Tumor Selective Ru(III) Schiff Bases Complexes, Discrimination of Ru(III)/Ru(II) Complexes in Solution: A DFT Study  Opening Ceremony Lecture

 

Emira Kahrović

Abstract: We recently reported a new Ru(III) complex (C1) with two Schiff bases and two chlorides that showed higher efficacy and improved cytotoxicity toward the triple-negative breast cancer cell line MDA-MB-231 compared to traditional antineoplastic drugs in use. In order to investigate hydrolysis as a possible activation step DFT method of electronic structure calculation was used to obtain a preliminary insight for C1 under the conditions of the predicted atomic/ionic/molecular environment. The presence of both Na(+) and Mg(2+) counterions and reducing agents in every cell plasma, give rise to several scenarios of C1 complexes interaction with living cell media. The DFT calculations showed the following: (i) the absolute energies of the complexes depend on the ruthenium oxidation state and the nature and type of association with the counter ion(s) (ii) the pairing of the C1-complex with the metal ion lowers the energy for solvated Mg(2+) compared to Na(+) (iii) the C1-Ru(II)/EtOH is more stable than the C1-Ru(III)/EtOH, and (iv) overall, the substitution of a chloride ligand by a water molecule is a thermodynamically unfavorable process. The proton from all Ru(III)Cl-OH2 species is more acidic compared to free water, consequently, under physiological conditions Ru(III)-ClOH2 does not exist. For Ru(II)-ClOH2 associated with Mg(2+) proton loss is a slightly  favored process. Simulated substitution of Ru(III)-ClCl to Ru(III)-ClOH2 and the corresponding Ru(II) species suggest the following trend: from the a prori thermodynamic point of view hydrolysis of the C1 complex ranges from unfavorable to significantly prohibitive. Based on these calculations, hydrolysis does not appear to be a significant activation step of C1 as a potential drug.

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 3.

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Reticular Nanoscience: Bottom-Up Assembly Nanotechnology Plenary lecture

 

Stefan Wuttke

Abstract: The chemistry of metal-organic and covalent organic frameworks (MOFs and COFs) is perhaps the most diverse and inclusive among the chemical sciences, and yet it can be radically expanded by blending it with nanotechnology. The result is reticular nanoscience, an area of reticular chemistry that has an immense potential in virtually any technological field. In this talk, we explore the extension of such an interdisciplinary reach by surveying the explored and unexplored possibilities that framework nanoparticles can offer. We localize these unique nanosized reticular materials at the juncture between the molecular and the macroscopic worlds, and describe the resulting synthetic and analytical chemistry, which is fundamentally different from conventional frameworks. Such differences are mirrored in the properties that reticular nanoparticles exhibit, which we described while referring to the present state-of-the-art and future promising applications in medicine, catalysis, energy- related applications, and sensors. Finally, the bottom-up approach of reticular nanoscience, inspired by nature, is brought to its full extension by introducing the concept of augmented reticular chemistry. Its approach departs from a single-particle scale to reach higher mesoscopic and even macroscopic dimensions, where framework nanoparticles become building units themselves and the resulting super-materials approach new levels of sophistication of structures and properties.

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 7.

 

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Element Accumulation in Mushrooms Plenary lecture

 

Walter Goessler

Abstract: Mushrooms are important in ecosystems as symbionts, saprotrophs, and parasites. The roles of fungi involve element cycling, rock and mineral transformations, bioweathering, fungal-clay interactions, and metal-fungal interactions. Therefore, fungi can also liberate elements from soil, effectively transform halogens, metals, metalloids, and organometallic compounds by reduction, methylation, and dealkylation. These processes are very important for our ecosystems since transformations of metal(loid)s modify their mobility and toxicity.

As it is really difficult to remove soil or rotted wood from the mycelium fruit bodies are mainly investigated for the transformed elements from soil. Moreover fruit-bodies serve as important nutrient source for parasites, wild animals, and also humans. It is not commonly known that fruit bodies may accumulate remarkable concentrations of (trace) elements. The well-known King Bolete (Boletus edulis) is known to accumulate the essential trace element selenium but on the other hand this fungus also accumulates significant amounts of mercury. This heavy metal is well known for its toxic properties. The Fly Agaric (Amanita muscaria) is a selective vanadium accumulator. Several 100s of mg V/kg dry mass have been determined during our studies. Thelephora penicillatawas found to be a cadmium accumulating mushroom (more than 1000 mg Cd/kg). Additionally, this mushroom accumulated high concentrations of arsenic. The Violet Crown Cup (Sarcosphaera coronaria), a mushroom considered edible in previous days, has been reported as an arsenic accumulator. We have determined close to 1 % of arsenic on a dry mass basis. Such concentrations are hardly ever reported for any natural living organism. The edible Ink Stain Bolete (Cyanoboletus pulverulentus) is also capable to accumulate up to 1300 mg As/kg. The False Chantarelle (Hygrophoropsis aurantiaca) was discovered to be an iron accumulating mushroom. Up to 5000 mg Fe/kg were found frequently in this species.As not all arsenic compounds have the same toxic properties it is necessary to determine the arsenic speciation. Our research provided new results with respect to the arsenic speciation in mushrooms. During our research we discovered several new arsenicals for the first time in living organisms. The presentation covers analytical aspects as well as the results for the total element determinations and the elemental speciation in different mushroom species.

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 8.

 

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Ruthenium Complexes as Antitumor Agents – Current Status and Perspective Plenary lecture

 

 

Sanja Grgurić Šipka

Abstract: The unique characteristics of metal-based compounds make them attractive as therapeutic and imaging agents. In the treatment of cancer, metal complexes have occupied an important place, helping to cure or prolong millions of lives. The most famous complex, cisplatin (cis-diamminedichloridoplatinum(II)), used alone or in combination therapy, is one of the most successful therapeutic metallodrugs discovered so far. Its limitations, such as drug resistance, limited spectrum of activity, and worsening side effects, have initiated efforts to critically consider other metal-based complexes with cytotoxic properties. Anticancer Ru complexes gained significant interest after two iconic Ru(III) complexes ̵-NAMI-A ((ImH)[trans-RuCl4(dmso-S)(Im)], Im = imidazole) and KP1339 (later renamed as IT-139 and BOLD-100, Na[trans-RuCl4(Ind)2], Ind = indazole)  - entered their first human clinical trials at the beginning of the 21st century. The successful completion of phase I and entry into phase II clinical trials of the phototherapeutic TLD1433 has further enhanced the role of Ru as a metal of choice for the design of new anticancer agents. Besides, the ruthenium(II)-arene motif, modifiable through mono- or bidentate ligands, and halide coordination also provide complexes with excellent antiproliferative activity. For instance, a variety of ruthenium(II)-arene complexes with dppz (dipyrido[3,2-a:2’,3’-c]phenazine-based ligands) also provides a promising strategy for developing potent antitumor agents. To conclude, ruthenium compounds hold significant promise due to their diverse structures, mechanism of action, and potential to overcome limitations associated with traditional anticancer agents. Top of Form

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 9.

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A Chemical Biology Toolkit to Understand and Target Biomolecular Condensates Keynote lecture

 

Anita Đonlić

Abstract: Cells organize functional processes into compartments to survive. Biomolecular condensates are unique compartments in that they can locally concentrate components to execute specific functions while lacking a surrounding membrane. As such, condensates dynamically respond to changes caused by stress, disease states, cell cycle stages, and drug treatments. These responses are reflected in microscopically-visible changes in condensate morphology; however, the link between a condensate’s (dys)function and its morphology change is not well understood.

The aim of this work was to understand the structure-function relationship of the nucleolus, the cell’s largest condensate and center of ribosome biogenesis. Specifically, we used a set of small molecule drugs to selectively inhibit different steps of ribosome assembly and observed distinct changes in nucleolar architecture by fluorescence microscopy. We then utilized this data as a training set to build a first-in-class deep neural network that accurately classifies drug-induced nucleolar morphology changes. Importantly, we demonstrated that the extent of nucleolar morphology disruption caused by these drugs can be quantified and used to predict the degree to which they perturb specific nucleolar processes. Next, we conducted a pilot drug screen to identify novel nucleolar phenotypes and nucleolar interaction networks. Given that nucleolar morphology and ribosome production are dysregulated in disease, current efforts are focused on clinically relevant applications of this technology. Together, this work demonstrates that automated imaging and deep learning-assisted analysis of condensate perturbations by small molecules can be used as a powerful discovery platform for new biology as well as for novel diagnostic and therapeutic development.

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 12.

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Anti-inflammatory Effects of Onion Bulb Extract in the Murine DSS-Colitis Model Keynote lecture

 

Maitham Abbas Ali Khajah

 

Abstract: The research is conducted asa contribution to existing literature to determine if onion bulb extract (OBE) reduces colitis severity in mice using treatment, prophylactic, and preventative approaches and the mechanism(s) responsible for these effects. Colitis was induced in mice by dextran sulfate sodium (DSS) daily administration in drinking water. For the treatment approach, mice received DSS for 4 days followed by daily i.p injections of OBE/vehicle administration for 3 days (without DSS administration). For the prophylactic approach, mice received daily i.p injections of OBE/vehicle along with DSS administration for 5 days. For the preventative approach, mice initially received daily i.p injections of OBE/vehicle for 7 days, followed by DSS administration for 5 days (without OBE/vehicle treatment). Colitis severity was determined at the gross and histological levels. The colonic level/activity of various cytokines and chemokines were measured using proteome profiling-based assays, western blotting, and immunofluorescence techniques. In vitro neutrophil superoxide release and survival were assessed by chemiluminescence and Annexin-V/7AAD assays, respectively. DSS-induced colitis was significantly reduced by OBE treatment using the three approaches at both gross and histological levels. OBE was also shown to reduce the colonic expression and activity of several pro-inflammatory molecules and signaling pathways, various cytokines and chemokines, and molecules involved in the apoptotic machinery.  In addition, OBE inhibited superoxide release and increased the spontaneous apoptosis of neutrophils. OBE showed anti-inflammatory actions, which are attributed, in part, to the modulation of the expression and activity of important pro-inflammatory molecules and signaling pathways involved in the inflammatory response.

 

Bulletin of the Chemists and Technologists of Bosnia and Herzegovina Special Issues, 16.