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In this work, for the first time, an approach was suggested for determining the pKa of triazolo[5,1-c][1,2,4]triazine compounds in N,N-dimethylformamide using potentiometric titration. It was noted that change in system potential in the titration curves of triazolo[5,1-с][1,2,4]triazine are observed for compounds containing either H+ located at the nitrogen atom in position 1 or an –NH2 group. The calculated pKa values of the studied molecules correspond to the pKa values of moderately strong acids and are in the range of 2–8. The relationship was established between the acidity of the heterocyclic fragment and the presence of electron donor substituents. The obtained pKa values of the compounds correlate with the calculated possible deprotonation centers of the molecule. It was found that determining the acidity constants of substances is useful for clarifying the mechanisms of their transformations. The possibility of establishing a relationship between the structure of the compound, pKa, and probable biological activity was shown.

The first example of the reaction of 5-nitro-8-hydroxyquinoline as a C-nucleophile with quinazoline is described. As a result of the reaction of C, C-coupling, a stable σ-adduct containing the drug nitroxalin on a heterocyclic carrier was obtained. The structure of the resulting adduct was confirmed by 2D 1H-13C HSQC, 1H-13C HMBC, and 1H-15N HMBC spectra.

Linked to Alzheimer’s disease (AD), amyloids and tau-protein are known to contain a large number of cysteine (Cys) residues. In addition, certain levels of some common biogenic thiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH), etc.) in biological fluids are closely related to AD as well as other diseases. Therefore, probes with a selective interaction with the above-mentioned thiols can be used for the monitoring and visualizing changes of (bio)thiols in the biological fluids as well as in the brain of animal models of Alzheimer’s disease. In this study, new Eu(III), Tb(III), Gd(III) and Sm(III) complexes of 2,2′-bipyridine ligands containing TEMPO fragments as receptor units for (bio)thiols are reported. The presence of free radical fragments of the ligand in the complexes was proved by using the electronic paramagnetic resonance (EPR) method. Among all the complexes, the Eu(III) complex turned out to be the most promising one as luminescence- and spin-probe for the detection of biogenic thiols. The EPR and fluorescent titration methods showed the interaction of the resulting complex with free Cys and GSH in solution. To study the practical applicability of the probes for the monitoring of AD in-vivo, by using the above-mentioned Eu(III)-based probe, the staining of the brain of mice with amyloidosis and Vero cell cultures supplemented with the cysteine-enriched medium was studied as well as the fluorescence titration of Bovine Serum Albumin, BSA (as the model for the thiol moieties containing protein), was carried out. Based on the results of fluorescence titration, the formation of a non-covalent inclusion complex between the above-mentioned Eu(III) complex and BSA was suggested.

A different type of MnO2-induced oxidative cyclization of dihydrotriazines has been developed. These dihydrotriazines are considered as a “formal” Schiff’s base. This method provided easy access to naphthofuro-fused triazine via the C-C/C-O oxidative coupling reaction. The reaction sequence comprised the nucleophilic addition of 2-naphthol or phenol to 1,2,4-triazine, followed by oxidative cyclization. The scope and limitations of this novel coupling reaction have been investigated. Further application of the synthesized compound has been demonstrated by synthesizing carbazole-substituted benzofuro-fused triazines. The scalability of the reaction was demonstrated at a 40 mmol load. The mechanistic study strongly suggests that this reaction proceeds through the formation of an O-coordinated manganese complex.