A series of new mono- and di-cationic 4,9-diazapyrenium derivatives were synthesized, for which in vitro anticancer activity has been demonstrated already. Their spectroscopic (NMR, electronic absorption and fluorescence) properties and the influence of positive charges, aromatic surface and substituents on the formation of stacked complexes with major nucleotides in water (this article) and on their interaction with nucleic acids (following article in this issue) was investigated. A reversible pH dependent formation of 5-hydroxy-4,9-diazapyrenium mono-pseudobase (DMOH) was observed for mono- and di-cationic 4,9-diazapyrenium derivatives in aqueous solution. The equilibrium constants, expressed as pK_DMOH, were determined. Binding of nucleotides (AMP, ADP, ATP, GMP and CMP) was studied in buffered (pH 5) aqueous solution by fluorescence. The formation of stacked nucleic base–diazapyrenium complexes with 1∶1 stoichiometry (log K_s 1.6–2.8) was observed. The stability constants were found to be independent of nucleotide charge, showing the dominance of aromatic stacking over coulombic interactions in such complexes. The presence of 6-phenyl and 5,10-diphenyl substituents on the phenanthridinium and 4,9-diazapyrenium systems, respectively, diminish nucleotide binding in both cases. The larger aromatic surface of the 4,9-diazapyrenium system, relative to the phenanthridinium (log K_s <1 to 2.3), does not considerably enhance nucleotide binding by the former. The nucleotide binding is somewhat stronger compared to neutral pyrene (log K_s 1.1–1.7) possessing a comparable aromatic surface. Singly charged 4,9-diazapyrenium derivatives bind nucleotides with a strength comparable to doubly charged 2,7-diazapyrenium derivatives. Some diazapyrenium derivatives exhibit high AMP/CMP selectivity (13, 11.7 and 15, 9.3) and moderate GMP/CMP selectivity (13, 6.0 and 12, 5.5). The observed selectivities are considerably higher than those exhibited by pyrene, ethidium or 2,7-diazapyrenium.

New fluorescent calix[4]arene derivatives 1, 2, and 3 were synthesized by introducing phenanthridine moieties at a lower calixarene rim. It was shown that due to the prominent fluorescence of compounds 1 and 3, they could be considered as potential sensitive fluorimetric cation sensors. Complexation of the prepared compounds with alkali-metal cations was studied at 25 °C in acetonitrile–dichloromethane and methanol–dichloromethane solvent mixtures (φ = 0.5) by means of fluorimetric, spectrophotometric, potentiometric, and microcalorimetric titrations as well as NMR spectroscopy. The stability constants of the corresponding complexes were determined, as were the enthalpies and entropies of the complexation reactions. In addition, equilibrium constants of ion-pairing reactions between alkali-metal cations and several anions in the solvents used were measured conductometrically. It was found that the cation-binding affinity of ligand 1 with four phenanthridine subunits was much higher than that of 2 and 3, with the complex stabilities in all cases being significantly lower in methanol–dichloromethane mixture compared to that in acetonitrile–dichloromethane. These findings were thoroughly discussed by taking into account the determined thermodynamic complexation data, structural properties of the ligand and free and complexed cations, as well as the solvation abilities of the solvents examined. The conclusions made in that way were corroborated by the results of the molecular dynamics simulations of the systems studied. An attempt to get an insight into the possible structures of the alkali-metal cation complexes with ligand 1 was made by carrying out the corresponding density functional theory calculations.

Novel calix[4]arene derivatives, 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(N-(2-(2-methoxyethoxy)ethyl)carbamoyl methoxy)calix[4]arene (1) and 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetra(N,N-bis(2-(2-methoxyethoxy)ethyl)carbamoyl methoxy)calix[4]arene (2), were prepared by introducing diethylene glycol subunits at the lower calixarene rim. The complexation affinities of these compounds towards alkali and alkaline earth metal cations were studied at 25 °C in acetonitrile and methanol by means of spectrophotometric, conductometric, and potentiometric titrations. The stability constants of the corresponding complexes with 1 : 1 (cation : ligand) stoichiometry were determined (in some cases only estimated), and their values obtained by different methods were in good agreement. The complexes with secondary-amide derivative (1) were observed to have much lower stabilities than those with tertiary-amide derivative (2). This was presumably mostly caused by the presence of intramolecular NH⋯OC hydrogen bonds in the former case. It was found that solvent significantly affected the stability of the complexes; the prepared calixarenes showed considerably higher affinities for cations in acetonitrile than in methanol. Generally, the ligands studied showed better binding abilities for alkaline earth cations than for alkali metal cations. The extraction of metal picrates from water to dichloromethane by the complexation of metal ions with ligands 1 and 2 was also investigated. In accordance with the complex stabilities, all cations were extracted fairly well (in some cases even excellently) with the tertiary-amide derivative, whereas this was not the case in the extraction experiments with the other ligand studied.