The role of CH/π interactions in the high affinity binding of streptavidin and biotin.

The streptavidin-biotin complex has an extraordinarily high affinity (Ka: 10mol) and contains one of the strongest non-covalent interactions known. This strong interaction is widely used in biological tools, including for affinity tags, detection, and immobilization of proteins. Although hydrogen bond networks and hydrophobic interactions have been proposed to explain this high affinity, the reasons for it remain poorly understood.

CH-π hydrogen bonds in biological macromolecules.

This is a sequel to the previous Perspective "The CH-π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates", which featured in a PCCP themed issue on "Weak Hydrogen Bonds - Strong Effects?": Phys. Chem.

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

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 origin of the generalized anomeric effect: possibility of CH/n and CH/pi hydrogen bonds.

Ab initio MO calculations were carried out at the MP4/6-311++G(3df,3pd)//MP2/6-311++G(3df,3pd) level to investigate the conformational Gibbs energy of a series of methyl ethers CH(3)O-CH(2)-X (X=OH, OCH(3), F, Cl, Br, CN, C triple bond CH, C(6)H(5), CHO). It was found that the Gibbs energy of the gauche conformers is lower in every case than that of the corresponding anti conformers. In the more stable gauche conformers, the interatomic distance between X and the hydrogen atom was shorter than the sum of the van der Waals radii.

Origin of the pi-facial stereoselectivity in the addition of nucleophilic reagents to chiral aliphatic ketones as evidenced by high-level ab initio molecular-orbital calculations.

Ab initio molecular-orbital (MO) calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy of alkyl 1-cyclohexylethyl ketones, cyclo-C6H11CHCH3-CO-R (R = Me, Et, iPr, and tBu). In each case, one of the equatorial conformations was shown to be the most stable. Conformers with the axial CHCH3COR group were also shown to be present in an appreciable concentration.

The anomeric effect revisited. A possible role of the CH/n hydrogen bond.

Ab initio MO calculations were carried out at the MP2/6-311++G(d,p) level to investigate the conformational energy of 2-substituted oxanes and 1,3-dioxanes. It has been found that the Gibbs free energies of the axial conformers are smaller than those of the corresponding equatorial conformers in every case when the 2-substituent Z is electron withdrawing (OCH(3), F, Cl, Br). The difference in Gibbs energy between the equatorial and axial conformers DeltaG(eq-ax) increases from Z=OCH(3) to F, Cl, and then to Br.

CH/pi hydrogen bonds as evidenced in the substrate specificity of acetylcholine esterase.

The crystal structure of acetylcholine esterase (AchE) in complex with various inhibitors, investigated as drugs for improvement of the cognitive ability of early stage Alzheimer's disease, has been analyzed with the use of our program CHPI. A number of CH/pi hydrogen bonds have been disclosed in the binding of the inhibitors with Torpedo californica AchE. It has been demonstrated that, in order to be effective in the binding with AchE, C-H bonds in the inhibitor need not be polarized.

Prevalence of the alkyl/phenyl-folded conformation in benzylic compounds C6H5CH2-X-R (X=O, CH2, CO, S, SO, SO2): significance of the CH/pi interaction as evidenced by high-level ab initio MO calculations.

Ab initio MO calculations were carried out to examine the conformational energies of various benzylic compounds C(6)H(5)CH(2)XR (X=O, CH(2), CO, S, SO, SO(2); R=CH(3), C(2)H(5), iC(3)H(7), tC(4)H(9)) at the MP2/6-311G(d,p)//MP2/6-31G(d) level. Rotamers with R/Ph in gauche relationship are generally more stable than the R/Ph anti rotamers. In these stable geometries, the interatomic distance in the interaction of alpha- or beta-CH in the alkyl group and the ipso-carbon atom of the phenyl ring is short.

Thymine-methyl/pi interaction implicated in the sequence-dependent deformability of DNA.

The crystal structures of deoxy-oligonucleotides were retrieved from the Nucleic Acid Database and analyzed with the use of our program CHPI. The structure of 5'-ApTpApT-3' has been shown to be stabilized by the 5-methyl group in the thymidine moiety that favorably interacts with the adenine pi-ring preceding it. H2' of the deoxyribose in adenine also interacts with the thymine ring next to it.