Noncovalent interactions have a constitutive role in the science of intermolecular relationships, particularly those involving aromatic rings such as π–π and cation–π. In recent years, anion–π contact has also been recognized as a noncovalent bonding interaction with important implications in chemical processes. Yet, its involvement in biological processes has been scarcely reported. Herein we present a large-scale PDB analysis of the occurrence of anion–π interactions in proteins and nucleic acids. In addition we have gone a step further by considering the existence of cooperativity effects through the inclusion of a second noncovalent interaction, i.e. π-stacking, T-shaped, or cation–π interactions to form anion–π–π and anion–π–cation triads. The statistical analysis of the thousands of identified interactions reveals striking selectivities and subtle cooperativity effects among the anions, π-systems, and cations in a biological context. The reported results stress the importance of anion–π interactions and the cooperativity that arises from ternary contacts in key biological processes, such as protein folding and function and nucleic acids–protein and protein–protein recognition. We include examples of anion–π interactions and triads putatively involved in enzymatic catalysis, epigenetic gene regulation, antigen–antibody recognition, and protein dimerization.

The controversial proposal that substituent effects in cation–π interactions can be attributed mainly to electrostatic effects between the ion and local dipoles has been theoretically studied by analyzing 171 aromatics interacting with Na+. Our results stress the importance of both electrostatic and π-polarization effects to properly describe cation–π interactions.

The adsorption of CO2 by zigzag and armchair single-walled carbon nanotubes (SWNTs) of different diameters (4.70–10.85 Å) has been studied using DFT with empirical dispersion correction (B97-D/SVP). Different binding sites have been considered, namely, in the interior (side-on and end-on binding modes) and on the surface (parallel or perpendicular) of the nanotube. Our calculations predict larger interaction energies for interior than exterior adsorption, with the strongest interactions observed for the (9,0) and (5,5) SWNTs (−12.8 and −12.5 kcal·mol–1, respectively). Therefore, these SWNTs can be considered to be very good potential candidates for carbon capture and storage in reducing CO2 emissions, as corroborated by the computed ΔH and ΔG adsorption energies. Moreover, we predict that interior adsorption would be more favorable than interstitial adsorption in bundles for (9,0), (10,0), (11,0), and (5,5) nanotubes. Furthemore, the diffusion of CO2 from the outside to the interior of the (5,5) SWNT is an energetically barrierless and favorable process. We have also analyzed the interplay between CO2·SWNT and CO2·CO2 interactions when more than one CO2 molecule is inside the tube, showing interesting cooperativity effects for SWNTs with large diameters. Finally, the symmetry-adapted perturbation theory partition scheme was used to investigate the physical nature of the interactions and to analyze the different energy contributions to the binding energy.

A conformational analysis of a synthetic model prodiginine was carried out. In solution this compound showed a strong preference for the β conformation, in which all the heterocycles are mutually cis. This conformation provided an ideal alignment of the three N–H groups for interacting with anions when the molecule is protonated. A different conformation was also detected in d6-DMSO for the mesylate salt, assigned to the α conformation, in which the C ring is engaged in an intramolecular hydrogen bond with the OMe group. The formation of a homodimer was observed in concentrated CDCl3 solutions of the neutral free base form of this prodiginine derivative. DFT calculations and the solid state structures of the hydrochloric and methanesulfonic acid salts were in good agreement with the results observed in solution. A complete study of the relative energies of different tautomers, isomers, and supramolecular complexes supported the preference for the β conformation both in water and in the gas phase.

The synthesis of octahedral copper and zinc coordination complexes containing ligands of the type 6R,2,4-bis(3,5-dimethylpyrazol-1-yl)triazine is described. They exhibit the simultaneous presence of C–H/π and anion–π interactions on both sides of the same triazine ring. When the pyrazolyl groups are not methylated, lone pair–π and anion–π interactions coexist on the same triazine ring. In addition, the interplay between C–H/π and anion–π interactions is studied by means of high level correlation ab initio calculations. They demonstrate that synergistic effects are present when both interactions coexist. These synergistic effects have been evaluated using the genuine non-additivity energies and symmetry adapted perturbation theory (SAPT).

The controversial proposal that substituent effects in cation–π interactions can be attributed mainly to electrostatic effects between the ion and local dipoles has been theoretically studied by analyzing 171 aromatics interacting with Na+. Our results stress the importance of both electrostatic and π-polarization effects to properly describe cation–π interactions.

Noncovalent interactions have a constitutive role in the science of intermolecular relationships, particularly those involving aromatic rings such as π–π and cation–π. In recent years, anion–π contact has also been recognized as a noncovalent bonding interaction with important implications in chemical processes. Yet, its involvement in biological processes has been scarcely reported. Herein we present a large-scale PDB analysis of the occurrence of anion–π interactions in proteins and nucleic acids. In addition we have gone a step further by considering the existence of cooperativity effects through the inclusion of a second noncovalent interaction, i.e. π-stacking, T-shaped, or cation–π interactions to form anion–π–π and anion–π–cation triads. The statistical analysis of the thousands of identified interactions reveals striking selectivities and subtle cooperativity effects among the anions, π-systems, and cations in a biological context. The reported results stress the importance of anion–π interactions and the cooperativity that arises from ternary contacts in key biological processes, such as protein folding and function and nucleic acids–protein and protein–protein recognition. We include examples of anion–π interactions and triads putatively involved in enzymatic catalysis, epigenetic gene regulation, antigen–antibody recognition, and protein dimerization.

Stable minima showing halogen bonds between charged molecules with the same sign have been explored by means of theoretical calculations. The dissociation transition states and their corresponding barriers have also been characterized. In all cases, the results indicate that the complexes are thermodynamically unstable but kinetically stable with respect to the isolated monomers in gas phase. A corrected binding energy profile by removing the charge–charge repulsion of the monomers shows a profile similar to the one observed for the dissociation of analogous neutral systems. The nature of the interaction in the minima and TSs has been analyzed using the symmetry adapted perturbation theory (SAPT) method. The results indicate the presence of local favorable electrostatic interactions in the minima that vanish in the TSs. Natural bond orbital (NBO) and “atoms-in-molecules” (AIM) theories were used to analyze the complexes, obtaining good correlations between Laplacian and electron density values with both bond distances and charge-transfer energy contributions E(2). The largest E(2) orbital interaction energies for cation–cation and anion–anion complexes are 561.2 and 197.9 kJ mol−1, respectively.

The synthesis of octahedral copper and zinc coordination complexes containing ligands of the type 6R,2,4-bis(3,5-dimethylpyrazol-1-yl)triazine is described. They exhibit the simultaneous presence of C–H/π and anion–π interactions on both sides of the same triazine ring. When the pyrazolyl groups are not methylated, lone pair–π and anion–π interactions coexist on the same triazine ring. In addition, the interplay between C–H/π and anion–π interactions is studied by means of high level correlation ab initio calculations. They demonstrate that synergistic effects are present when both interactions coexist. These synergistic effects have been evaluated using the genuine non-additivity energies and symmetry adapted perturbation theory (SAPT).