Abstract. Algae to the rheological properties of alginates, one of the main products obtained from algae, these polysaccharides are widely used in fields such as pharmaceuticals, medical technology, cosmetics, food, agriculture, textile and paper industry. Therefore, sodium alginate was obtained from waterweed (Charophyceae) in the following experiment. The structure and composition of sodium alginate were analyzed using physical and chemical research methods: IR spectroscopy and XRD.

Liposomes are artificial vesicles encapsulating the drug moiety. The structural adaptability of liposomes has been employed to make them drug carriers for smart delivery systems, improving bioavailability, stability, target delivery, etc. However, conventional liposomes have some drawbacks, like limited payload, shorter in vivo circulatory lifespan, unregulated releasing properties, rapid clearance from bloodstream etc. Polymeric modification of the liposomes addressed and effectively overcome all the drawbacks of conventional liposomes. Polymeric materials offers indefinite structural diversity thus a substantial portion of the materials has been employed for drug-targeting methods and controlled drug release. Conjugation of liposomes and polymers develops a hybrid vesicle with intermediary physicochemical and stimulus responsive properties (pH, temperature, etc.). The reliability of liposomes with respect to pH, nature of drug moiety, enzyme, and immune response can be strengthened by polymers. Polymer modified liposomes also enhances pharmacokinetic and pharmacodynamic profile of the drug moiety. The forms of polymer, cross-linking agents, interaction, and bonding used during polymerization of liposomes have an impact on their activity. According to the extensive review of the literature that is accessible in the different data sources, research in this field is proactively involved in the synthesis of newer polymeric materials, and the supramolecular structuring of the different chemicals.

Aromatic heterocycles can be found in many molecules endowed with specific properties, in particular for applications in the fields of medicinal chemistry and materials. In the group, we notably develop synthetic methodologies to selectively introduce iodine onto aromatic compounds and to use this heavy halogen in order to build heterocycles of interest. While we sometimes employed direct iodinations on electron-enriched aromatic compounds, we mainly optimized deprotometallation-iodolysis sequences to functionalize substrates sensitive to nucleophilic attacks. In particular, hindered lithium amide-metal trap tandems have been designed to overcome the low tolerance of some functional groups (e.g. ketones or sensitive diazines) toward organolithiums. The aromatic iodides generated these ways have been involved in transition metal-catalyzed cross-couplings to access original scaffolds (oxazoloquinoxalines, pyrazinoisatins, pyrazinocarbazoles, benzo(thio)pyranoquinazolines...). We especially developed the use of aromatic iodides in copper-mediated N-arylation of anilines, e.g. to reach triarylamines. Combined with subsequent cyclizations, these reactions allowed an access to numerous heterocyclic compounds (such as acridones, acridines, other aza-aromatic polycycles and helicene-like structures) with potential applications. From some of the scaffolds obtained, biological evaluation in the frame of collaborations allowed properties of interest to be discovered (e.g. specific inhibition of protein kinases GSK-3 or PIM, related to cancer development).

Derivatives of 1,3,4-thiadiazole are of great interest for scientific and practical human activities as biologically active substances, dyes, components for creating semiconductors, energy accumulators, liquid crystals, polymers, nanomaterials, etc. Here we report the synthesis of 2,4-dichloro-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide based on N,N’-disubstituted hydrazinecarbothioamide - 2,4-dichloro-N-(2,2,2-trichloro-1-(2-(phenylcarbamothioyl)hydrazine-1-carbothioamido)ethyl)benzamide. The method for obtaining the target product is based on the dehydrosulfurization reaction of the starting hydrazinecarbothioamide under the action of a mixture of iodine and triethylamine in a DMF medium. A new derivative of 1,3,4-thiadiazole was obtained in 84% yield, and its structure was confirmed by ¹H and ¹³C NMR spectroscopy data. Molecular docking studies were carried out with the structure of the resulting compound and dihydrofolate reductase (DHFR) in the AutoDock Vina program. The resulting compound is a potential inhibitor of DHFR and surpasses several known analogues in terms of the strength of the complex formed with the active site of this enzyme.

Introduction: The emergence of resistant strains of viruses, recurrence of diseases, ineffectiveness of known drugs against the latent form of infection, encourage scientists to seek new means of prevention and treatment of such infection. Incorporation of the fluorine atom into compounds can impact their solubility and lipophilicity, and affect their biological potency. The aim of this study was to elucidate the impact of fluorine-containing thiosugars on herpetic and adenoviral infections. Methodology: The toxicity of trifluoromethylthiolane derivatives: 2-hydroxy-2-trifluoromethylthiolane (10S52) or 3-hydroxy-2-(hydroxymethyl)-trifluoromethylthiolane (SBIO6) was evaluated using changes in cell viability and metabolic activity. The antiviral activity against herpes simplex virus type 1 (HSV-1) and human adenovirus type 2 (HAdV-2) was assessed using a virus yield reduction assay. Results: Some cytotoxic effect of SBIO6 and 10S52 compounds on BHK-21and Hep-2 cells was detected, CC₅₀ values were in ranging 161-670 µg/ml. It was found that compound 10S52 significantly inhibited HSV-1 reproduction, reducing the virus titer obtained de novo by 1.7 lg. Such activity indicates that virus offspring are formed but virus particles are not complete and they are not able to cause an infection process. Whereas for adenoviral infection such effect was not detected. Conclusion: Thus, the 2-hydroxy-2-trifluoromethylthiolane may be a potential tool for the development of agents for the treatment of HSV-1 infections. Funding: This work was supported by scientific project of NAS of Ukraine “Patterns of influence of chemical, natural and physical virus-inactivating agents on biological processes in the virus-cell system”.

Chitosan is a natural polysaccharide that is mainly obtained from the shell of marine crustaceans including crabs, lobsters, shrimps, etc. Chitosan has been widely used in biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. However, owing to the limited solubility of CS in water, its water-soluble derivatives are preferred for the mentioned applications. Carboxymethyl chitosan (CMC) is one of the water-soluble derivatives of chitosan, which has antibacterial, anti-cancer, anti-tumor, anti-fungal, and antioxidant properties and is used in both drug delivery and enzyme delivery. This material is also utilized in tissue engineering, wound healing and bioimaging. For these reasons, in this article, different and novel methods by employing KI catalyst and/or ultrasonication are accomplished for the synthesis of valuable CMC.

Metal-organic framework Zn₂ (BDC)₂ (DABCO) was employed as a reusable heterogeneous acidic catalyst in the acylation reaction of various benzaldehydes with acetic anhydride under microwave irradiation. The outstanding features of this efficient solvent-free method are short reaction time, ease of product separation, greatest yields, and the ability to reuse the catalyst several times.

Heterocyclic compounds are one of the most important organic compounds, that frequently present as active pharmaceuticals products. Among them, nitrogen-containing heterocycles have attracted much interest from various researchers due to their wide range of biological activities. Considering the importance of all these characteristics and the very pronounced application, and as a continuation of our work on pyrazolines, this paper shows the synthesis of some new N-acyl pyrazolines in very good yields. These products were obtained by reacting chalcone analogues with hydrazine in the presence of boiling formic or acetic acid.

Transition metal-catalyzed, “ligand free” P–C coupling reactions under MW conditions

Bianka Huszár¹, Renáta Szolga¹, Nóra Á. Szűcs¹, Zoltán Mucsi¹, György Keglevich¹

¹Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, e-mail: huszar.bianka@vbk.bme.hu

Transition metal-catalyzed, cross coupling reaction is a good choice to form a P–C bond. The first P–C coupling reactions were carried out between vinyl- or aryl halides and dialkyl phosphites in the presence of Pd(PPh₃)₄ catalyst by Hirao et al.. To replace the rather expensive Pd(PPh₃)₄, different types of Pd-precursors (e.g. Pd(OAc)₂, PdCl₂) or Pd-complexes (e.g. Pd(dba)₂) were used together with P-ligands (e.g. PPh₃, dppp). In these cases, the active catalyst was formed in situ. Later on, microwave (MW)-assisted reactions and several Ni- and Cu-catalyzed coupling reactions were also described.

Keglevich and co-workers developed a “P-ligand free”, Pd(OAc)₂ or NiCl₂-catalyzed, MW-assisted procedure, where no usual P-ligands, meaning cost, were added, instead, the excess of the >P(O)H-reagents served as P-ligands via there trivalent tautomeric form. The mechanism of the coupling reactions was explored by quantum chemical calculations. Furthermore, it was found that there is an inductive period, during which the active catalyst is formed. In our latest work, the Pd(OAc)₂-catalyzed, “ligand free” method was extended to dihalogenobenzenes. After the Pd- and Ni-catalyzed accomplishments, the Cu(I) and Cu(II)-catalyzed “ligand free” P–C coupling reactions were also studied under MW conditions. These mechanisms were also explored by quantum chemical calculations.

The 2,5-DKP are heterocyclic peptidomimetics, present in nature with high structural diversity, privileged in the design of new bioactive molecules with potential application in medicinal chemistry, exhibiting anticancer and antimicrobial properties, among others. Conventional synthetic approaches to access DKPs via dipeptide ester cyclization suffer from several disadvantages, for example; low overall yields, use of a large number of reagents and/or drastic reaction conditions, among others. Therefore, in the present work, we report the one-pot synthesis of 2,5-DKP by RMC-I coupled with a cyclic post-transformation process with several advantages over previously reported conventional methods.