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Data on the synthesis, complexing ability, practical applications, and biological activity of dibenzotetraazamacroheterocycles of the azacrown ether, amide, and azomethinedibenzotetraazacycloalkane types and also dibenzotetraazamacroheterocycles containing amide and azomethine fragments are classified and analyzed.At present the chemistry of nitrogen macrocycles is developing at a very high rate. Many of the compounds are highly effective extractants for metal ions [1-3], find widespread use as contrast agents for magnetic resonance imaging [4][5][6][7][8], and can also be used as precursors in the biosynthesis of certain types of alkaloids [9] and also as ion-selective [10] and fluorescent [11] receptors and as agents for the transport of ions through a liquid membrane in dialysis and electrodialysis [12,13]. Chiral macrocyclic tetraamides are used as stationary phase in liquid chromatography [14]. The potentialities of nitrogen macrocycles in theoretical and practical respects have not been exhausted, and further research in the field is promising.In the last 15 years there have been a fairly large number of monographs and reviews in which aspects of the synthesis, properties, and applications of azamacroheterocycles and their metal complexes have been touched upon [15][16][17][18][19][20][21][22][23][24][25][26]. However, there have been significantly fewer publications devoted to the various classes of dibenzotetraazamacroheterocycles (e.g., dibenzotetraaza [14]annulenes [27][28][29], macrocyclic Schiff bases based on 2,6-diformylphenols [30]). Dibenzotetraazamacroheterocycles have found use as effective extractants for metal ions and as spectrophotometric agents [31][32][33], are used in the design of new magnetic materials [34], etc. To fill the gap we considered it desirable to analyze existing published material on the synthesis, complexation, and practical applications of dibenzotetraazamacrocycles of the azacrown ether, amide, azomethine, and dibenzotetraazacycloalkane types and also dibenzotetraazamacrocycles containing amide and azomethine fragments.

Synthetic and natural ionophores have been developed to catalyze ion transport and have been shown to exhibit a variety of biological effects. We synthesized 24 aza- and diaza-crown ethers containing adamantyl, adamantylalkyl, aminomethylbenzoyl, and ε-aminocaproyl substituents and analyzed their biological effects in vitro. Ten of the compounds (8, 10–17, and 21) increased intracellular calcium ([Ca2+]i) in human neutrophils, with the most potent being compound 15 (N,N’-bis[2-(1-adamantyl)acetyl]-4,10-diaza-15-crown-5), suggesting that these compounds could alter normal neutrophil [Ca2+]i flux. Indeed, a number of these compounds (i.e., 8, 10–17, and 21) inhibited [Ca2+]i flux in human neutrophils activated by N-formyl peptide (fMLF). Some of these compounds also inhibited chemotactic peptide-induced [Ca2+]i flux in HL60 cells transfected with N-formyl peptide receptor 1 or 2 (FPR1 or FPR2). In addition, several of the active compounds inhibited neutrophil reactive oxygen species production induced by phorbol 12-myristate 13-acetate (PMA) and neutrophil chemotaxis toward fMLF, as both of these processes are highly dependent on regulated [Ca2+]i flux. Quantum chemical calculations were performed on five structure-related diaza-crown ethers and their complexes with Ca2+, Na+, and K+ to obtain a set of molecular electronic properties and to correlate these properties with biological activity. According to density-functional theory (DFT) modeling, Ca2+ ions were more effectively bound by these compounds versus Na+ and K+. The DFT-optimized structures of the ligand-Ca2+ complexes and quantitative structure–activity relationship (QSAR) analysis showed that the carbonyl oxygen atoms of the N,N’-diacylated diaza-crown ethers participated in cation binding and could play an important role in Ca2+ transfer. Thus, our modeling experiments provide a molecular basis to explain at least part of the ionophore mechanism of biological action of aza-crown ethers.