On the directionality of anion-π interactions

The directionality of two important noncovalent interactions involving aromatic rings (namely anion-π and cation-π) is investigated. It has been recently published that the anion-π interactions observed in X-ray structures where the anion is located exactly over the center of the ring are scarce compared to cation-π interactions. To explain this behavior, we have analyzed how the interaction energy (RI-MP2/aug-cc-pVDZ level of theory) is affected by moving the anion from the center of the ring to several directions in anion-π complexes of chloride with either hexafluorobenzene or trifluoro-s-triazine. We have compared the results with the directionality of the cation-π interaction in the sodium-benzene complex. The results are useful to explain the experimental differences between both ion-π interactions. We have also computed the van der Waals radii of several halide anions and we have compared them to the neutral halogen atoms.     

CH-anion versus anion-π interactions in the crystal and in solution of pentafluorobenzyl phosphonium salts

A series of phosphonium salts with pentafluorobenzyl substituents have been synthesized and were investigated in the crystal as well as in solution. The solid state structures of 1a, 1b and 2d reveal the presence of anion-π as well as CH-anion interactions. The two attractive, yet competitive forces seem to act in concert and a directing effect of the CH interaction on the relative position between anion and π-system is observed. The search for anion-π interactions in solution failed. Only CH-anion interactions proved to be important in solution.     

Putting anion-π interactions into perspective

Supramolecular chemistry is a field of scientific exploration that probes the relationship between molecular structure and function. It is the chemistry of the noncovalent bond, which forms the basis of highly specific recognition, transport, and regulation events that actuate biological processes. The classic design principles of supramolecular chemistry include strong, directional interactions like hydrogen bonding, halogen bonding, and cation-π complexation, as well as less directional forces like ion pairing, π-π, solvophobic, and van der Waals potentials. In recent years, the anion-π interaction (an attractive force between an electron-deficient aromatic π system and an anion) has been recognized as a hitherto unexplored noncovalent bond, the nature of which has been interpreted through both experimental and theoretical investigations. The design of selective anion receptors and channels based on this interaction represent important advances in the field of supramolecular chemistry. The objectives of this Review are 1) to discuss current thinking on the nature of this interaction, 2) to survey key experimental work in which anion-π bonding is demonstrated, and 3) to provide insights into the directional nature of anion-π contact in X-ray crystal structures.     

Combined cation-π and anion-π interactions for zwitterion recognition

Brothers and enemies: Anion-π and cation-π interactions act in a synergistic way when gathered in the molecular cavity of a hemicryptophane host, affording an efficient contribution (-170?kJ?mol(-1)) in zwitterion recognition. NMR titration experiments and calculations reveal the positioning of the guest in the cavity of the heteroditopic receptor. This study emphasizes the importance of anion-π bonds in host-guest chemistry.     

Al4(2-); the anion-π interactions and aromaticity in the presence of counter ions

The influence of presence of counter ions and π-complexation with benzene on the bonding and magnetic properties of Al(4)(2-), the most studied all-metal cluster, is studied here. It is shown that complexation by either counter ions or benzene decreases the delocalization index between Al atoms and the magnitude of bond magnetizability, that is a Quantum Theory of Atoms in Molecules, QTAIM, -based magnetic index of aromaticity. Benzene forms two types of π-complexes with the Al(4) framework; CH-π (T-shaped) complexes and parallel π-π stacking (PPS) complexes. It is shown that variation in the π-charge of the Al(4) framework affects the relative stability of the T-shaped/PPS complexes. Free Al(4)(2-) forms a stable T-shaped anion-π complex with benzene but in the presence of cations, formation of PPS complexes is more favourable, energetically. It is suggested that this property could be used for designing molecular switches and tuneable anion sensors.     

Unexpected nonadditivity effects in anion-π complexes

Several complexes of fluorine-substituted ethyne, ethene, butadiene, benzene, and [n]radialenes (n = 3-5) with two anions have been optimized at the RI-MP2/aug-cc-pVTZ level of theory. The additivity of the anion-π interaction was studied depending on the number of double bonds and fluorine atoms. Interesting nonadditivity effects were observed in the aromatic and antiaromatic complexes, which were analyzed by partitioning the total interaction energy into individual components, using Bader's theory of "atoms in molecules" and changes in the aromatic character of the ring upon complexation.     

A computational study of cation-π interactions in polycyclic systems: exploring the dependence on the curvature and electronic factors

Density functional theory (B3LYP) calculations with double and triple-ζ quality basis sets were performed on the Li⁺ and Na⁺ π-complexes of corannulene 2, sumanene 3CH₂, heterosumanenes 3X, triphenylene 4 and heterotrindenes 5X. The metal ions bind to both convex and concave faces of buckybowls, with a consistent preference to bind to the convex surface by about 1-4 kcal/mol. The metal ion complexation with the π-framework of the central six-membered ring span wider range compared to benzene, indicating the control of size, curvature and electronic perturbations over the strength of cation-π interactions. Computations show that the bowl-to-bowl inversion barriers are only slightly altered upon metal complexation, indicating the continuity of bowl-to-bowl inversion despite metal complexation. We have calculated the binding energies of model systems, triphenylene (4) and heterotrindenes (5X), which indicate that the interaction energies are controlled by electronic factors. While the inversion barrier is dependent mainly on the size of the heteroatom, the extent of binding is independent of the size of the atom or the bowl depth.     

Energetic effects between halogen bonds and anion-π or lone pair-π interactions: a theoretical study

Energetic effects between halogen bonds and anion-π or lone pair-π interactions have been investigated by means of ab initio MP2 calculations. 1,4-diiodo-perfluorobenzene, a very effective building block for crystal engineering based on halogen bonding, is selected in this work both as electron-deficient π aromatic ring and as halogen bond donor. Additive and diminutive effects are observed when halogen bonds and anion-π/lone pair-π interactions coexist in the same complex, which can be ascribed to the same direction of charge transfer for the two interactions. These effects have been analyzed in detail by the structural, energetic, and AIM properties of the complexes. Finally, experimental evidence of the combination of the interactions has been obtained from the Cambridge Structural Database.     

The strength and selectivity of perfluorinated nano-hoops and buckybowls for anion binding and the nature of anion-π interactions

Perfluorinated cycloparaphenylenes (F-[n]CPP, n = 5–8), boron nitride nanohoop (F-[5]BNNH), and buckybowls (F-BBs) were proposed as anion receptors via anion-π interactions with halide anions (Cl⁻, Br⁻ and I⁻), and remarkable binding strengths up to −294.8 kJ/mol were computationally verified. The energy decomposition approach based on the block-localized wavefunction method, which combines the computational efficiency of molecular orbital theory and the chemical intuition of ab initio valence bond theory, was applied to the above anion-π complexes, in order to elucidate the nature and selectivity of these interactions. The overall attraction is mainly governed by the frozen energy component, in which the electrostatic interaction is included. Remarkable binding strengths with F-[n]CPPs can be attributed to the accumulated anion-π interactions between the anion and each conjugated ring on the hoop, while for F-BBs, additional stability results from the curved frameworks, which distribute electron densities unequally on π-faces. Interestingly, the strongest host was proved to be the F-[5]BNNH, which exhibits the most significant anisotropy of the electrostatic potential surface due to the difference in the electronegativities of nitrogen and boron. The selectivity of each host for anions was explored and the importance of the often-overlooked Pauli exchange repulsion was illustrated. Chloride anion turns out to be the most favorable anion for all receptors, due to the smallest ionic radius and the weakest destabilizing Pauli exchange repulsion.     

Cooperativity of H-bonding and anion-π interaction in the binding of anions with neutral π-acceptors

A rare anion-π complex between bromide and a neutral receptor is reported and related receptor systems are studied with a series of anions. The interaction is observed in the solid state and in solution, and further evidence for it is obtained by a computational study.     

From attraction to repulsion: anion-π interactions between bromide and fluorinated phenyl groups

Anion-π interactions in crystals of fluorobenzyl ammonium salts depend on the degree of fluorination at the aromatics.     

Contribution of cation-π interactions in iminium catalysis

Ab initio calculations were carried out for a benzyl-substituted iminium cation derived from (E)-crotonaldehyde and a chiral imidazolidinone that was developed as an organocatalyst by MacMillan et al. At the MP2 level of theory it is predicted that the phenyl group is close to the iminium moiety in the most stable conformer, suggesting that the cation-π interaction contributes to the stabilization of this conformer. Energy decomposition analyses on model systems indicate that the electrostatic and polarization terms make significant contribution to the attractive interactions between the benzene ring and the iminium cation.     

Induction-driven stabilization of the anion-π interaction in electron-rich aromatics as the key to fluoride inclusion in imidazolium-cage receptors

Intermolecular interactions that involve aromatic rings are key processes in both chemical and biological recognition. It is common knowledge that the existence of anion-π interactions between anions and electron-deficient (π-acidic) aromatics indicates that electron-rich (π-basic) aromatics are expected to be repulsive to anions due to their electron-donating character. Here we report the first concrete theoretical and experimental evidence of the anion-π interaction between electron-rich alkylbenzene rings and a fluoride ion in CH(3)CN. The cyclophane cavity bridged with three naphthoimidazolium groups selectively complexes a fluoride ion by means of a combination of anion-π interactions and (C-H)(+)···F(-)-type ionic hydrogen bonds. (1)H NMR, (19)F NMR, and fluorescence spectra of 1 and 2 with fluoride ions are examined to show that only 2 can host a fluoride ion in the cavity between two alkylbenzene rings to form a sandwich complex. In addition, the cage compounds can serve as highly selective and ratiometric fluorescent sensors for a fluoride ion. With the addition of 1 equiv of F(-), a strongly increased fluorescence emission centered at 385 nm appears at the expense of the fluorescence emission of 2 centered at 474 nm. Finally, isothermal titration calorimetry (ITC) experiments were performed to obtain the binding constants of the compounds 1 and 2 with F(-) as well as Gibbs free energy. The 2-F(-) complex is more stable than the 1-F(-) complex by 1.87 kcal mol(-1), which is attributable to the stronger anion-π interaction between F(-) and triethylbenzene.     

Substituent effects in synthetic lectins--exploring the role of CH-π interactions in carbohydrate recognition

Contacts between aromatic surfaces and saccharide CH groups are common motifs in natural carbohydrate recognition. These CH-π interactions are modeled in "synthetic lectins" which employ oligophenyl units as apolar surfaces. Here we report the synthesis and study of new synthetic lectins with fluoro- and hydroxy-substituted biphenyl units, designed to explore the role of π-electron density in carbohydrate CH-π interactions. We find evidence that recognition can be moderated through electronic effects but that other factors such as cavity hydration are also important and sometimes predominant in determining binding strengths.     

Effects of the biological backbone on stacking interactions at DNA-protein interfaces: the interplay between the backbone···π and π···π components

The (gas-phase) MP2/6-31G*(0.25) π···π stacking interactions between the five natural bases and the aromatic amino acids calculated using (truncated) monomers composed of conjugated rings and/or (extended) monomers containing the biological backbone (either the protein backbone or deoxyribose sugar) were previously compared. Although preliminary energetic results indicated that the protein backbone strengthens, while the deoxyribose sugar either strengthens or weakens, the interaction calculated using truncated models, the reasons for these effects were unknown. The present work explains these observations by dissecting the interaction energy of the extended complexes into individual backbone···π and π···π components. Our calculations reveal that the total interaction energy of the extended complex can be predicted as a sum of the backbone···π and π···π components, which indicates that the biological backbone does not significantly affect the ring system through π-polarization. Instead, we find that the backbone can indirectly affect the magnitude of the π···π contribution by changing the relative ring orientations in extended dimers compared with truncated dimers. Furthermore, the strengths of the individual backbone···π contributions are determined to be significant (up to 18 kJ mol(-1)). Therefore, the origin of the energetic change upon model extension is found to result from a balance between an additional (attractive) backbone···π component and differences in the strength of the π···π interaction. In addition, to understand the effects of the biological backbone on the stacking interactions at DNA-protein interfaces in nature, we analyzed the stacking interactions found in select DNA-protein crystal structures, and verified that an additive approach can be used to examine the strength of these interactions in biological complexes. Interestingly, although the presence of attractive backbone···π contacts is qualitatively confirmed using the quantum theory of atoms in molecules (QTAIM), QTAIM electron density analysis is unable to quantitatively predict the additive relationship of these interactions. Most importantly, this work reveals that both the backbone···π and π···π components must be carefully considered to accurately determine the overall stability of DNA-protein assemblies.     

π-π interactions in the self-assembly of melamine and barbituric acid derivatives

Self-assembly of a pair of complementary molecular components, 5-(4-dodecyloxyben-zylidene)-(1H,3H)-2,4,6-pyrimidinetrione (PB12) and 4-amino-2,6-didodecylamino-1, 3, 5-triazine (M12) was studied by cyclic voltammogram, surface photovoltage spectroscopy, fluorescence spectroscopy, FTIR and X-ray diffraction. It is found that after mixing equimolar amount of PB12 and M12 at room temperature, not only triply complementary hydrogen bonds are formed between PB12 and M12 but also further self-assembly of the supermolecules based on network of hydrogen bonds occurs via π-π interactions. During the self-assembly of the supermolecules, π-π interactions are induced by delocalized interactions between the HOMO of M12 and the LUMO of PB12, resulting in the formation of a supramolecular nanotube with a layered structure bearing a d value of 0.41 nm and PB12 and M12are arranged alternatively between adjacent supermolecules.     

π-π interactions in the self-assembly of melamine and barbituric acid derivatives

Self-assembly of a pair of complementary molecular components, 5-(4-dodecyloxyben-zylidene)-(1H,3H)-2, 4,6-pyrimidinetrione (PB₁₂)and 4-amino-2,6-didodecylamino-1, 3, 5-triazine (M₁₂) was studied by cyclic voltammogram, surface photovoltage spectroscopy, fluorescence spectroscopy, FTIR and X-ray diffraction. It is found that after mixing equimolar amount of PB₁₂ and M₁₂ at room temperature, not only triply complementary hydrogen bonds are formed between PB₁₂and M₁₂ but also further self-assembly of the supermolecules based on network of hydrogen bonds occurs via π-π interactions. During the self-assembly of the supermolecules, π -π interactions are induced by delocalized interactions between the HOMO of M₁₂ and the LUMO of PB₁₂, resulting in the formation of a supramolecular nanotube with a layered structure bearing a d value of 0.41 nm and PB₁₂ and M₁₂are arranged alternatively between adjacent supermolecules.     

Research progress in cation-π interactions

Cation-π interaction is a potent intermolecular interaction between a cation and an aromatic system,which has been viewed as a new kind of binding force,as being compared with the classical interactions(e.g. hydrogen bonding,electrostatic and hydrophobic interactions). Cation-π interactions have been observed in a wide range of biological contexts. In this paper,we present an overview of the typical cation-π interactions in biological systems,the experimental and theoretical investigations on cation-π interactions,as well as the research results on cation-π interactions in our group.     

Syntheses and Br…π supramolecular interactions in the crystal structure of ipriflavone bromides

Supramolecular forces, including electrostatic in- teraction, hydrogen bond, hydrophobic interaction and aromatic stacking interaction, are the important re- search area in supramolecular chemistry and crystal engineering[1]. Aromatic stacking interaction…