The nature and characteristics of the CH/π interaction are discussed by comparison with other weak molecular forces such as the CH/O and OH/π interaction. The CH/π interaction is a kind of hydrogen bond operating between a soft acid CH and a soft base π-system (double and triple bonds, C6 and C5 aromatic rings, heteroaromatics, convex surfaces of fullerenes and nanotubes). The consequences of CH/π hydrogen bonds in supramolecular chemistry are reviewed on grounds of recent crystallographic findings and database analyses. The topics include intramolecular interactions, crystal packing (organic and organometallic compounds), host/guest complexes (cavity-type inclusion compounds of cyclodextrins and synthetic macrocyclic hosts such as calixarenes, catenanes, rotaxanes and pseudorotaxanes), lattice-inclusion type clathrates (including liquid crystals, porphyrin derivatives, cyclopentadienyl compounds and C60 fullerenes), enantioselective clathrate formation, catalytic enantioface discriminating reactions and solid-state photoreaction. The implications of the CH/π concept for crystal engineering and drug design are evident.

CH/π hydrogen bonds in crystals

Supramolecular chemistry has expanded dramatically in recent years both in terms of potential applications and in its relevance to analogous biological systems. The formation and function of supramolecular complexes occur through a multiplicity of often difficult to differentiate noncovalent forces. The aim of this Review is to describe the crucial interaction mechanisms in context, and thus classify the entire subject. In most cases, organic host-guest complexes have been selected as examples, but biologically relevant problems are also considered. An understanding and quantification of intermolecular interactions is of importance both for the rational planning of new supramolecular systems, including intelligent materials, as well as for developing new biologically active agents.

Binding Mechanisms in Supramolecular Complexes

The CH/π hydrogen bond is an attractive molecular force occurring between a soft acid and a soft base. Contribution from the dispersion energy is important in typical cases where aliphatic or aromatic CH groups are involved. Coulombic energy is of minor importance as compared to the other weak hydrogen bonds. The hydrogen bond nature of this force, however, has been confirmed by AIM analyses. The dual characteristic of the CH/π hydrogen bond is the basis for ubiquitous existence of this force in various fields of chemistry. A salient feature is that the CH/π hydrogen bond works cooperatively. Another significant point is that it works in nonpolar as well as polar, protic solvents such as water. The interaction energy depends on the nature of the molecular fragments, CH as well as π-groups: the stronger the proton donating ability of the CH group, the larger the stabilizing effect. This Perspective focuses on the consequence of this molecular force in the conformation of organic compounds and supramolecular chemistry. Implication of the CH/π hydrogen bond extends to the specificity of molecular recognition or selectivity in organic reactions, polymer science, surface phenomena and interactions involving proteins. Many problems, unsettled to date, will become clearer in the light of the CH/π paradigm.

The CH/π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates

I. Characterization of Hydrogen Bonding: From van der Waals Interactions to Covalency, R. Parthasarathi and V. Subramanian II. Intramolecular Hydrogen Bonds. Methodologies and Strategies for their Strength Evaluation, Giuseppe Buemi III. Changes of Electron Properties in the Formation of Hydrogen Bonds, Luis F. Pacios IV. Weak to Strong Hydrogen Bonds, Han Myoung Lee, N. Jiten Singh, Kwang S. Kim V. The Nature of the C-H...X Intermolecular Interactions in Molecular Crystals. A Theoretical Perspective, Fernando Mota, Emiliana D'Oria VI. Weak hydrogen bonds involving transition elements, Maria Jose Calhorda VII. Contribution of CH**X Hydrogen Bonds to Biomolecular Structure, Steve Scheiner VIII. Neutral Blue-Shifting and Blue-Shifted Hydrogen Bonds, Eugene S. Kryachko IX. Hydrogen-Hydrogen Bonding: the Non-Electrostatic Limit of Closed-Shell Interaction Between two Hydrogen Atoms (A Review), Cherif F. Matta X. Potential Energy Shape for the Proton Motion in Hydrogen Bonds Reflected in Infrared and NMR Spectra, Gleb S. Denisov, Janez Mavri and Lucjan Sobczyk XI. Molecular Geometry - Distant Consequences of H-Bonding, Tadeusz M. Krygowski and Joanna E. Zachara XII. Topology of X-ray charge density of hydrogen bonds, Tibor S. Koritsanszky XIII. Structure-Property Relations for Hydrogen-Bonded Solids, Andrzej Katrusiak XIV. Unrevealing the Nature of Hydrogen Bonds: p -Electron delocalization Shapes H-Bond Features. Intramolecular and Intermolecular Resonance-Assisted Hydrogen Bonds, Slawomir J.Grabowski and Jerzy Leszczynski

Hydrogen Bonding - New Insights

C-h⋯π-interactions in proteins

CH/π Interactions as demonstrated in the crystal structure of guanine-nucleotide binding proteins, Src homology-2 domains and human growth hormone in complex with their specific ligands

CH/π interactions in the crystal structure of class I MHC antigens and their complexes with peptides

Intramolecular CH-? interaction. Substituent effect as a probe for hydrogen bond-like character

The CH/π-interaction is a weak hydrogen bond occurring between CH groups and π-electron systems. Evidence for such a weak attractive molecular force has been presented. These include data from IR, NMR, CD spectroscopies, and X-ray crystallography. The conclusion has been supported by ab initio MO calculations. An important point is that CH- and π-groups are arranged generally in chemical structures and have many chance to interact each other. Unlike ordinary hydrogen bondings, the CH/π interaction may occur in protic media as well as in nonpolar atmosphere. Consequences in supramolecular chemistry, selectivities in chemical reactions, as well as the substrate specificities of proteins were discussed in the light of the CH/π-interaction hypothesis.

https://www.jstage.jst.go.jp/article/yukigoseikyokaishi1943/55/1/55_1_2/_pdf

The CH/π Interaction. Implications in Molecular Recognition

Crystal Structure of (S)-α-Methyltyrosinato-(SSSR)-[(2R,5R,8R,11R)-2,5,8,11- tetraethyl-1,4,7,10-tetraazacyclododecane]cobalt(III) Bromide Perchlorate Dihydrate

Motohiro Nishio

Papers

CH/π Interactions as demonstrated in the crystal structure of guanine-nucleotide binding proteins, Src homology-2 domains and human growth hormone in complex with their specific ligands

CH/π interactions in the crystal structure of class I MHC antigens and their complexes with peptides

Intramolecular CH-? interaction. Substituent effect as a probe for hydrogen bond-like character

The CH/π Interaction. Implications in Molecular Recognition

Crystal Structure of (S)-α-Methyltyrosinato-(SSSR)-[(2R,5R,8R,11R)-2,5,8,11- tetraethyl-1,4,7,10-tetraazacyclododecane]cobalt(III) Bromide Perchlorate Dihydrate