Matija Modrušan

DFT and MD calculations reveal that cation coordination within 1,2- and 1,3-alternate calix[4]arene binding sites varies with ion size and charge density, resulting in endo - and exo -complexes, while solvation also strongly affects their structures.

Complexation of alkaline earth metal cations with fluorescent tertiary-amide lower-rim calix[4]arene derivative bearing two phenanthridine moieties was studied experimentally (UV spectrophotometry, fluorimetry, isothermal microcalorimetry, NMR spectroscopy) and computationally (classical molecular dynamics and DFT calculations) at 25 °C. The complexation reactions were studied in acetonitrile, methanol, and ethanol, whereby the solvent effect on cation-binding processes was particularly addressed. The complex stability constants and standard reaction thermodynamic quantities (Gibbs energies, enthalpies, and entropies) were determined. The receptor exhibited particularly high affinity towards alkaline earth metal cations in acetonitrile, with peak affinity for Ca²⁺. The stability of all complexes was significantly lower in ethanol and methanol, where the most stable complex was formed with Sr²⁺. The decrease in cation-binding abilities was a consequence of the differences in solvation of the reactants and products of the complexation reactions (involving inclusion of the solvent molecule in the calixarene cone), cation charge density, as well as the cation–ligand binding site compatibility. The reactions were enthalpically controlled in acetonitrile, whereas in methanol and ethanol, the binding processes were endothermic and thus entropy driven. The results of ¹H NMR measurements, MD simulations, and DFT calculations provided an insight into the structure of the complexes and the corresponding adducts with solvent molecules, as well as the structural aspects behind the differences in complexation thermodynamics. Due to the significant increase in its fluorescence upon cation binding, the studied calixarene derivative was proven to be a promising luminescent sensor for alkaline earth metal cations.

Complexation of alkaline earth metal cations with fluorescent tertiary-amide lower-rim calix[4]arene derivative bearing two phenanthridine moieties was studied experimentally (UV spectrophotometry, fluorimetry, isothermal microcalorimetry, NMR spectroscopy) and computationally (classical molecular dynamics and DFT calculations) at 25 °C. The complexation reactions were studied in acetonitrile, methanol, and ethanol, whereby the solvent effect on cation-binding processes was particularly addressed. The complex stability constants and standard reaction thermodynamic quantities (Gibbs energies, enthalpies, and entropies) were determined. The receptor exhibited particularly high affinity towards alkaline earth metal cations in acetonitrile, with peak affinity for Ca2+. The stability of all complexes was significantly lower in ethanol and methanol, where the most stable complex was formed with Sr2+. The decrease in cation-binding abilities was a consequence of the differences in solvation of the reactants and products of the complexation reactions (involving inclusion of the solvent molecule in the calixarene cone), cation charge density, as well as the cation-ligand binding site compatibility. The reactions were enthalpically controlled in acetonitrile, whereas in methanol and ethanol the binding processes were endothermic, and thus entropy driven. The results of 1H NMR measurements, MD simulations, and DFT calculations provided an insight into the structure of the complexes and the corresponding adducts with solvent molecules, as well as on the structural aspects behind the differences in complexation thermodynamics. Due to the significant increase of its fluorescence upon cation binding, the studied calixarene derivative was proven to be a promising luminescent sensor for alkaline earth metal cations.

A comprehensive thermodynamic and structural study of the complexation affinities of tetra (L1), penta (L2), and hexaphenylalanine (L3) linear peptides towards several inorganic anions in acetonitrile (MeCN) and N,N-dimethylformamide (DMF) was carried out. The influence of the chain length on the complexation thermodynamics and structural changes upon anion binding are particularly addressed here. The complexation processes were characterized by means of spectrofluorimetric, ¹H NMR, microcalorimetric, and circular dichroism spectroscopy titrations. The results indicate that all three peptides formed complexes of 1:1 stoichiometry with chloride, bromide, hydrogen sulfate, dihydrogen phosphate (DHP), and nitrate anions in acetonitrile and DMF. In the case of hydrogen sulfate and DHP, anion complexes of higher stoichiometries were observed as well, namely those with 1:2 and 2:1 (peptide:anion) complexes. Anion-induced peptide backbone structural changes were studied by molecular dynamic simulations. The anions interacted with backbone amide protons and one of the N-terminal amine protons through hydrogen bonding. Due to the anion binding, the main chain of the studied peptides changed its conformation from elongated to quasi-cyclic in all 1:1 complexes. The accomplishment of such a conformation is especially important for cyclopeptide synthesis in the head-to-tail macrocyclization step, since it is most suitable for ring closure. In addition, the studied peptides can act as versatile ionophores, facilitating transmembrane anion transport.

The affinity of novel, phenanthridine-based calix[4]arene glycoconjugate (L), bearing efficient cation-binding tertiary-amide functionalities in the coordination site, towards alkali and alkaline earth metal cations in methanol was investigated by me...

Cyclic pentaphenylalanine was studied as an efficient anion sensor for halides, thiocyanate and oxoanions in acetonitrile and methanol. Stability constants of the corresponding complexes were determined by means of fluorimetric, spectrophotometric, ¹H NMR, and microcalorimetric titrations. A detailed structural overview of receptor–anion complexes was obtained by classical molecular dynamics (MD) simulations. The results of ¹H NMR and MD studies indicated that the bound anions were coordinated by the amide groups of cyclopeptide, as expected. Circular dichroism (CD) titrations were also carried out in acetonitrile. To the best of our knowledge, this is the first example of the detection of anion binding by cyclopeptide using CD spectroscopy. The CD spectra were calculated from the structures obtained by MD simulations and were qualitatively in agreement with the experimental data. The stoichiometry of almost all complexes was 1:1 (receptor:anion), except for dihydrogen phosphate where the binding of dihydrogen phosphate dimer was observed in acetonitrile. The affinity of the cyclopeptide receptor was correlated with the structure of anion coordination sphere, as well as with the solvation properties of the examined solvents.

The binding of alkali metal cations with two tertiary-amide lower-rim calix[4]arenes was studied in methanol, N,N-dimethylformamide, and acetonitrile in order to explore the role of triazole and glucose functionalities in the coordination reactions. The standard thermodynamic complexation parameters were determined microcalorimetrically and spectrophotometrically. On the basis of receptor dissolution enthalpies and the literature data, the enthalpies for transfer of reactants and products between the solvents were calculated. The solvent inclusion within a calixarene hydrophobic basket was explored by means of ¹H NMR spectroscopy. Classical molecular dynamics of the calixarene ligands and their complexes were carried out as well. The affinity of receptors for cations in methanol and N,N-dimethylformamide was quite similar, irrespective of whether they contained glucose subunits or not. This indicated that sugar moieties did not participate or influence the cation binding. All studied reactions were enthalpically controlled. The peak affinity of receptors for sodium cation was noticed in all complexation media. The complex stabilities were the highest in acetonitrile, followed by methanol and N,N-dimethylformamide. The solubilities of receptors were greatly affected by the presence of sugar subunits. The medium effect on the affinities of calixarene derivatives towards cations was thoroughly discussed regarding the structural properties and solvation abilities of the investigated solvents.