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

Although supramolecular chemistry and noncovalent interactions are playing an increasingly important role in modern chemical research, a detailed understanding of prototype noncovalent interactions remains lacking. In particular, π−π interactions, which are ubiquitous in biological systems, are not fully understood in terms of their strength, geometrical dependence, substituent effects, or fundamental physical nature. However, state-of-the-art quantum chemical methods are beginning to provide answers to these questions. Coupled-cluster theory through perturbative triple excitations in conjunction with large basis sets and extrapolations to the complete basis set limit have provided definitive results for the binding energy of several configurations of the benzene dimer, and benchmark-quality ab initio potential curves are being used to calibrate new density functional and force-field models for π−π interactions. Studies of substituted benzene dimers indicate flaws in the conventional wisdom about substitu...

High-Accuracy Quantum Mechanical Studies of π−π Interactions in Benzene Dimers

Sandwich and T-shaped configurations of benzene dimer, benzene−phenol, benzene−toluene, benzene−fluorobenzene, and benzene−benzonitrile are studied by coupled-cluster theory to elucidate how substituents tune π−π interactions. All substituted sandwich dimers bind more strongly than benzene dimer, whereas the T-shaped configurations bind more or less favorably depending on the substituent. Symmetry-adapted perturbation theory (SAPT) indicates that electrostatic, dispersion, induction, and exchange-repulsion contributions are all significant to the overall binding energies, and all but induction are important in determining relative energies. Models of π-π interactions based solely on electrostatics, such as the Hunter-Sanders rules, do not seem capable of explaining the energetic ordering of the dimers considered.

Substituent Effects in π−π Interactions: Sandwich and T-Shaped Configurations

This treatise is an update to a preceding highlight (CH/π hydrogen bonds in crystals) published in this journal 5 years ago (M. Nishio, CrystEngComm, 2004, 6, 130–156). After the introductory part (sections 1 and 2), we survey recent results (mostly since 2004) relevant to the CH/π hydrogen bond: crystal conformation, packing and host/guest chemistry (section 3). Section 4 summarizes the results obtained by crystallographic database (CSD and PDB) analyses. In section 5, several topics in related fields (selectivity in organic reactions, surface chemistry, structural biology, drug design and high-level ab initio calculations of protein/substrate complexes and natural organic compounds) are introduced, and in the final part we comment on the prospects of this emerging field of chemistry.

CH/π hydrogen bonds in organic and organometallic chemistry

Palladium catalysed allylic substitution has emerged as one of the more useful synthetic methods for the construction of C-C and C-X bonds. The reaction offers the advantages of mild reaction conditions, as well as the ability to accomodate a wide range of nucleophiles and their electrophilic partners. The issues of regiocontrol, diastereocontrol and enantiocontrol have been documented by a number of researchers over the last twenty years. The levels of selectivity in many cases are very high, and current research is driving these selectivities higher still. A greater understanding of the nature of the process is occurring as more detailed mechanistic and structural studies are being undertaken. Many uses have been found for palladium catalysed allylic substitution methodology, since the strong stereocontrol allows for the selective formation of numerous products. A few other metals are also able to catalyse allylic substitution, with modified stereochemical behaviour, although these are currently less well documented than for palladium catalysed process.

Selectivity in palladium catalysed allylic substitution

Quantum mechanical and quantum mechanical/molecular mechanical calculations in conjunction with continuum solvation models have been used to analyze CH-π interactions in model systems of aryl- and alkyl-aromatic interactions, as well as in a model folding system designed to study those interactions. High level calculations reproduced accurately the interaction of CH-π interactions in both alkyl- and aryl-based model systems. Dispersion effects dominate the interaction, but the electrostatics term is also relevant for aryl CH-π interactions. Theoretical calculations were also used to examine the influence of CH-π interactions in determining the conformational flexibilitty of folding models. Finally, a critical comparison of the results obtained from high level calculations on model systems and the experimental data derived for folding models in apolar solvents was carried out, which allowed us to reconcile the apparent discrepancy found between both data.

Theoretical Study of Alkyl-π and Aryl-π Interactions. Reconciling Theory and Experiment

The biological mechanisms involved in non-contact musculoskeletal soft tissue injuries (NCMSTI) are poorly understood. Genetic risk factors may be associated with susceptibility to injuries, and may exert marked influence on recovery times. Data on type and degree of injury and recovery time were collected in 73 male professional soccer players (43 White, 11 Black Africans and 19 Hispanics) who suffered total of 242 injuries (203 muscle, 24 ligament, and 15 tendon injuries). One single nucleotide polymorphism (SNPs) in the following genes were analyzed: Elastin (ELN); Titin (TTN); SRY-related HMG-box (SOX15); Insulin-like growth factor 2 (IGF2); Chemokine, CC motif, ligand 2 (CCL2); Collagen type 1 alpha 1(COL1A1); Collagen type 5 alpha 1 (COL5A1), and Tenascin C (TNC). There was evidence of a statistically significant association between the degree of injury and the IGF2 genotype (P = 0.034). In addition, there was evidence of a statistically significant association between the degree of muscle injury and CCL2 (P = 0.026) Finally, there was evidence of a statistically significant association between ELN and degree of injury (p = 0.009) and recovery time (P = 0.043). There was no evidence of a statistically significant association between any of the genes studied and degree of injury or recovery time for tendon injuries. SNPs in the IGF2, CCL2, and ELN genes may be associated to the degree and recovery time of NCMSTI.

/pdf/single-nucleotide-polymorphisms-associated-with-non-contact-2wlcht30um.pdf

Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time

Jordi Ribas

Papers

Theoretical Study of Alkyl-π and Aryl-π Interactions. Reconciling Theory and Experiment

Single nucleotide polymorphisms associated with non-contact soft tissue injuries in elite professional soccer players: influence on degree of injury and recovery time

Palladium-catalyzed C-alkylations of the highly acidic and enolic triacetic acid lactone. Mechanism and stereochemistry

Electronic effects in the regioselectivity of nucleophilic attacks on cationic 1,3-diaryl-π-allylpalladium complexes

Palladium catalyzed c-allylation of highly acidic carbo and heterocyclic β-dicarbonyl compounds