An Integrated Approach (Thermodynamic, Structural, and Computational) to the Study of Complexation of Alkali-Metal Cations by a Lower-Rim Calix[4]arene Amide Derivative in Acetonitrile

Abstract

The calix[4]arene secondary-amide derivative L was synthesized, and its complexation with alkali-metal cations in acetonitrile (MeCN) was studied by means of spectrophotometric, NMR, conductometric, and microcalorimetric titrations at 25 °C. The stability constants of the 1:1 (metal/ligand) complexes determined by different methods were in excellent agreement. For the complexation of M(+) (M = Li, Na, K) with L, both enthalpic and entropic contributions were favorable, with their values and mutual relations being quite strongly dependent on the cation. The enthalpic and overall stability was the largest in the case of the sodium complex. Molecular and crystal structures of free L, its methanol and MeCN solvates, the sodium complex, and its MeCN solvate were determined by single-crystal X-ray diffraction. The inclusion of a MeCN molecule in the calixarene hydrophobic cavity was observed both in solution and in the solid state. This specific interaction was found to be stronger in the case of metal complexes compared to the free ligand because of the better preorganization of the hydrophobic cone to accept the solvent molecule. Density functional theory calculations showed that the flattened cone conformation (C(2) point group) of L was generally more favorable than the square cone conformation (C(4) point group). In the complex with Na(+), L was in square cone conformation, whereas in its adduct with MeCN, the conformation was slightly distorted from the full symmetry. These conformations were in agreement with those observed in the solid state. The classical molecular dynamics simulations indicated that the MeCN molecule enters the L hydrophobic cavity of both the free ligand and its alkali-metal complexes. The inclusion of MeCN in the cone of free L was accompanied by the conformational change from C(2) to C(4) symmetry. As in solution studies, in the case of ML(+) complexes, an allosteric effect was observed: the ligand was already in the appropriate square cone conformation to bind the solvent molecule, allowing it to more easily and faster enter the calixarene cavity.

Complexation of Oxonium and Ammonium Ions by Lower-rim Calix[4]arene Amino Acid Derivatives

“…After 1.66 ns for ligand 1 and 0.28 ns for ligand 2, an inclusion of acetonitrile molecule in the calixarene hydrophobic cone was observed ( Figures S1 and S2). Unlike in the case of the calix [4]arene secondary-amide derivative which we studied earlier, 11 after the inclusion of solvent molecule in 1 and 2 the shape of the cone remained somewhat flattened, although it resembled the regular square cone conformation. This deviation from C 4 symmetry is most likely due to the steric effects of the large substituents at the lower rim of the herein investigated ligands.…”

“…Apart from the cation size, the binding process is often strongly influenced by the solvation of the reactants and the complex formed [8][9][10] . In acetonitrile, the inclusion of a solvent molecule into the calixarene hydrophobic cavity [10][11][12][13][14][15][16][17] was shown to be synergetic with the cation complexation. In the derivatives having substituents with secondary amide groups the presence of intramolecular NH···O=C hydrogen bonds considerably reduces the ionophoric activity of macrocycles compared to tertiary amide derivatives.…”

Complexation of Alkali Metal Cations by a Tertiary Amide Calix[4]Arene Derivative in Strongly Cation Solvating Solvents

“…ester, ketone, and amide derivatives) have been affirmed as highly effective receptors due to a well-defined binding site with numerous donor atoms directed towards the guest. [4,5,8,15,16,17] Among these derivatives, the compounds comprising tertiary-amide groups proved to be the most efficient, exhibiting remarkably high affinities towards alkali metal cations. [4,5,17,18] The selectivity of the calixarenebased receptors is in great part a result of size complementarity of host cavity and the cation.…”

“…Namely, a significant change in solvation of both receptor and the cation is expected upon complexation, since the solvent molecules surrounding the cation are mostly replaced by the donor atoms of the ligand. [16,17] Thus, one of the prerequisites of further rational receptor design with the aim of improving their properties and obtaining high affinity, coupled with peak selectivity, is understanding the thermodynamics of the binding process, including the solvation influence, in as much detail as possible. This agenda requires extending the corresponding reasearch to most diverse media (solvents) in order to define specific requirements, and determine drawbacks and advantages in different systems.…”

An Enchiridion of Supramolecular Thermodynamics: Calix[N]arene (N=4,5,6) Tertiary Amide Derivatives and their Ionic Recognition

“…Recently a detailed study on the interactions of a lower rim calix [4]arene containing secondary amide functionalities with alkali-metal cations involving thermodynamic, structural and computational studies has been reported. 30 Even though the receptor does not involve a tertiary amide it is worth mentioning this paper given that an integrated approach has been taken for complexation studies. This is encouraging in view of the fact that in most cases only qualitative data sets have been reported on calix[n]arene tertiary amide derivatives and metal cations.…”