REVIEWS
M. Nishio, Phys. Chem. Chem. Phys. 2011, 13, 13873-13900. DOI: 10.1039/C1CP20404A (PCCP Perspective, themed issue ‘Weak Hydrogen Bonds - Strong Effects)
The CH/pi hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates.
The CH/pi 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/pi hydrogen bond is the basis for ubiquitous existence of this force in various fields of chemistry. A salient feature is that the CH/pi 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 pi-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/pi 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/pi paradigm.
O. Takahashi, Y. Kohno, M. Nishio, Chem. Rev. 2010, 110, 6049-6076: Relevance of Weak Hydrogen Bonds in the Conformation of Organic Compounds and Bioconjugates: Evidence from Recent Experimental Data and High-Level ab Initio MO Calculations.
1. Introduction
1.1. Conformation of Organic Compounds
1.2. Folded Conformation
2. Importance of Weak Hydrogen Bonds
2.1. Hydrogen Bond
2.2. Weak Hydrogen Bonds
2.2.1. CH/n Hydrogen Bond
2.2.2. XH/pi Hydrogen Bonds
2.3. CH/pi Hydrogen Bond
2.4. Directionality and Cooperativity of the CH/piHydrogen Bond
3. Preference of the Folded Conformer in Synthetic Organic Compounds
3.1. Relevance of the CH/n Hydrogen Bond in Organic Compounds
3.1.1. CH3/C=O Eclipsed Conformation
3.1.2. Conformation of Methyl Ethers CH3OCH2X
3.1.3. Conformation of Alkyl Halides
3.1.4. Conformation of Alcohols and Ethers
3.1.5. Conformation of Cyclohexane and Cyclohexanone Derivatives
3.1.6. The Anomeric Effect Revisited
3.2. Relevance of the XH/pi (X = O, S, Se) Hydrogen Bond in Organic Compounds
3.2.1. Conformation of Simple Unsaturated Molecules
3.3. CH/pi Hydrogen Bonds
3.3.1. Conformation of Simple Unsaturated Molecules
3.3.2. Conformation of Alkylbenzenes and Related Molecules
3.3.3. Conformation of Alkyl 1-Phenylethyl Ketones
3.3.4. Cram Rule Revisited
3.4. Aromatic CH/pi Hydrogen Bond
3.4.1. Folded Ar/Ar Conformation
3.4.2. Nature of the Aromatic CH/pi Hydrogen Bond
4. Conformation of Natural Organic Compounds Studied by ab Initio MO Calculations
4.1. The Alkylketone Effect Revisited
4.2. Conformation of Isomenthone and Isocarvomenthone
4.3. Stability of the Axial Isopropyl Group in Ketosteroids
4.4. Conformation of alpha-Phellandrene
4.5. Conformation of Levopimaric Acid
5. Preference of the Gauche Alkyl Aromatic Conformation as Evidenced by Crystallographic Database Studies
5.1. Organic Compounds
5.2. Coordination and Organometallic Compounds
5.3. Peptides
5.4. Combined CSD and Computational Study
6. CH/pi Hydrogen Bonds in Biologically Important Molecules
6.1. CH/pi Hydrogen Bonds in Enantiomeric Separation
6.2. Conformation of Peptides
6.2.1. Solution Conformation
6.2.2. Solid Conformation
6.3. Relevance of CH/pi Hydrogen Bonds in Bioconjugates
7. Summary and Outlook
M. Nishio, Y. Umezawa, K. Honda, S. Tsuboyama and H. Suezawa, CrystEngComm 2009, 11, 1757-1788, CH/pi hydrogen bonds in organic and organometallic chemistry (Dedicated to Dr Olga Kennard)
This treatise is an update to a preceding highlight (CH/pi 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/pi 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 prospect of this emerging field of chemistry.
T. Ozawa, K. Okazaki and M. Nishio. FMO as a Tool for Structure-Based Drug Design, Chapter 10 inThe Fragment Molecular Orbital Method: Practical Applications to Large Molecular Systems. Eds. D. G. Fedorov and K. Kitaura, CRC Press, New York 2009
1. A Brief Review of Weak Molecular Interaction
2. Application of Fragment Molecular Orbital (FMO) to Drug Design
3. Dependence of IFIE's on the Basis Sets
4. Conclusion
M. Nishio, Y. Umezawa, Topics in Stereochemistry 2006, 25, 255-302:
The CH/pi Hydrogen Bond: An Important Molecular Force in Controlling the Crystal Conformation of Organic Compounds and Three-Dimensional Structure of Biopolymers (dedicated to the memory of Professor Derek H. R. Barton and Professor Max. F. Perutz)
1. Introduction: 1.1 Four types of hydrogen bonds. 1.2 The CH/pi hydrogen bond. 1.3 Characteristics of the CH/pi hydrogen bond
2. Conformation of organic compounds: 2.1 Organic compounds. 2.2 Peptides (2.2.1 Cyclic peptides. 2.2.2 Acyclic peptides)
3. Interligand interactions in coordination and organometallic compounds: 3.1 Coordination compounds. 3.2 Transition metal compounds. 3.3 CH/pi hydrogen bonds implicated in the mechanism of enantioselective catalytic reactions
4. Three-dimensional structure of biopolymers: 4.1 Proteins. 4.2 Nucleic acids
5. Database studies: 5.1 Compounds of small molecular weight. 5.2 Biopolymers
6. Conclusion
Tetrahedron Report No. 724 (dedicated to the memory of Sir Derek H. R. Barton)
M. Nishio, Tetrahedron 2005, 61, 6923-6950: CH/pi hydrogen bonds in organic reactions
The origin of the stereoselectivity of organic reactions such as Diels-Alder reactions, topochemical photoreactions, diastereoface- and enantioface-discriminating reactions and enantioselective catalytic reactions with transition metal complexes has been explored in the context of the CH/pi hydrogen bond. The ground-state conformation of the reacting molecules, where CH/pi hydrogen bonds play the central role, has been suggested to be the most important factor in controlling the stereoselectivity of the reactions. The underlying concept of the Cram and the Prelog rule was critically examined and a hypothesis has been presented that the p-facial selectivity is understood in terms of the conformational preference of the substrates. The contribution from the CH/pi and CH/O hydrogen bonds has been suggested to be indispensable.
M. Nishio, CrystEngComm 2004, 6, 130-158: CH/pi hydrogen bonds in crystals (dedicated to Professor Rocco Ungaro)
The nature and characteristics of the CH/pi interaction are discussed by comparison with other weak molecular forces such as the CH/O and OH/pi interaction. The CH/pi interaction is a kind of hydrogen bond operating between a soft acid CH and a soft base pi-system (double and triple bonds, C6 and C5 aromatic rings, heteroaromatics, convex surfaces of fullerenes and nanotubes). The consequences of CH/pi 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/pi concept for crystal engineering and drug design are evident.
M. Nishio, Weak Hydrogen Bonds in Encyclopedia of Supramolecular Chemistry, 2004, 1576-1585, Eds. J. L. Atwood and J. W. Steed, Marcel Dekker Inc.
1. Introduction
2. Detection of Weak Hydrogen Bonds (2.1 Spectroscopy, 2.2 Crystallography, 2.3 Database Analyses, 2.4 Theoretical Calculation)
3. Hydrogen Bonds between hard acids and soft bases
4. Hydrogen Bonds between soft acids and hard bases
5. Hydrogen Bonds between soft acids and soft bases
6. Summary and Prospect
ARTICLES
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Tetrahedron 2009, 65, 3525-3528: The conformation of levopimaric acid investigated by high-level ab initio MO calculations. Possibility of the CH/pi hydrogen bond.
Ab initio MO calculations were carried out, at the MP2/6-311G(d,p) level of approximation, to investigate the conformation of levopimaric acid. It has been found that the folded conformation is more stable than the extended conformation. The result is consistent with the documented experimental data. The reason for the relative stability of the folded conformation has been sought in the context of the CH/p hydrogen bond. Short non-bond distances have been disclosed between CHs in the 10b angular methyl group and sp2-carbons of the conjugated diene ring in the more stable folded conformers of model compounds. We suggest that the folded conformation of levopimaric acid is a consequence of an attractive molecular force, the CH/p hydrogen bond.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Carbohydr. Res. 2009, in press: Origin of the generalized anomeric effect: Possibility of the 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 CH3OCH2X (X = OH, OCH3, F, Cl, Br, CN, C?CH, C6H5, CHO). It has been 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 hydrogen atom has been found to be shorter than the sum of the van der Waals radii. Natural bonding orbital (NBO) charges of the group X are more negative in the gauche conformers than those in the anti conformers. In view of the above findings, we suggest that the CH/n and CH/p hydrogen bonds play an important role in stabilizing the gauche conformation of these compounds. Implication of the present result to the generalized anomeric effect is discussed.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Bull. Chem. Soc. Jpn. 2009, 82, 272-276: The Origin of the Relative Stability of Axial Conformers of Cyclohexane and Cyclohexanone Derivatives: Importance of the CH/n and CH/pi Hydrogen Bonds
Ab initio MO calculations were carried out, at the MP2/6-311++G(d,p) level, to investigate the Gibbs energy of conformational isomers of cyclohexanes cyclo-C6H11X 3 and cyclohexanones cyclo-C6H9OX 4. In 3, it has been found that the conformer bearing an electron-withdrawing group X (OCH3, F, Cl, Br) at the axial orientation is relatively stable as compared to corresponding alkyl cyclohexanes; the result is consistent with documented experimental data. For X = CCH and CN, the axial conformer has been suggested to be slightly more stable. In 4, the axial conformer has been found to be more stable than the equatorial conformer, except for X = OH. Short non-bond distances have been disclosed in every axial conformer of 3 and 4, between axial CHs of the cyclohexane ring and X. The reason for the relative stability of the axial conformers has been sought in the context of the CH/n and CH/p hydrogen bonds. We suggest that a considerable part of the relative stability of the axial conformation is attributed to intramolecular CH/n and CH/p hydrogen bonds. Natural bonding orbital charges of the relevant atoms are consistent with the above suggestion.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Tetrahedron 2008, 64, 5773-5778: Origin of the Axial-Alkyl Preference of (R)-alpha-Phellandrene and Related Compounds Investigated by High-Level Ab Initio MO Calculations. Importance of the CH/pi Hydrogen Bond.
Ab initio MO calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-311G(d,p) level, to investigate the Gibbs energy of conformational isomers of (R)-alpha-phellandrene and related 5-alkyl-1,3-cyclohexadienes. It has been found that the conformer bearing the 5-alkyl group in axial orientation is more stable than the equatorial congener. The result is consistent with experimental evidence that the axial-isopropyl conformer prevails in the conformational equilibrium of alpha-phellandrene. The reason for the stability of the folded conformer has been sought in the context of the CH/pi hydrogen bond. A number of short non-bond distances have been disclosed in the axial conformers, between CHs in the 5-alkyl group and sp2-carbons of the cyclohexadiene ring. The helical sense of the conjugated dienes in the axial conformers has been shown to be left-handed, whereas that of the equatorial conformers is right-handed. We suggest that the stability of the folded conformation often observed in conjugated diene compounds of natural origin, such as alpha-phellandrene and levopimaric acid, is attributed to an attractive molecular force, the CH/pi hydrogen bond.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Youji Kurihara, Kazuyoshi Ueda, Yoji Umezawa, Hiroko Suezawa, Motohiro Nishio, Tetrahedron 2008, 64, 2433-2440: The Conformation of alkyl cyclohexanones and terpenic ketones. Interpretation for the“Alkylketone Effect”based on the CH/pi(C=O) hydrogen bond.
Ab initio MO calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-311G(d,p) level, to investigate the Gibbs free energy of the conformational isomers of 2-alkyl, 3-alkyl, and 4-alkyl cyclohexanones. The calculation gave results consistent with the general trend experimentally found. The genesis of stabilization of the axial conformers in 2- and 3-alkyl cyclohexanones, as compared to the structurally corresponding cyclohexane derivatives, was sought in the context of the attractive CH/pi(C=O) hydrogen bond. In support of this hypothesis, short nonbond distances have been noted between CHs in the alkyl group and the carbonyl carbon in the relevant axial conformers. Calculations were also carried out to study the conformational energies of several terpenic ketones. For isomenthone, more than a half molecular fraction (ca. 55%) has been suggested to be in the isopropyl-axial conformation, while for isocarvomenthone ca. 77% has been suggested to be in the axial-isopropyl conformation; this is consistent with bibliographic experimental data. A crystallographic database search has provided results compatible with this conclusion. We suggest that the relative stability of the axial alkyl substituent, often observed in terpenic and steroidal ketones is rationalized in terms of an attractive molecular force, the CH/pi(C=O) hydrogen bond.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Chem. Phys. Lett. 2007, 440, 64-69: Origin of the gauche preference of n-propyl halides and related molecules investigated by ab initio MO calculations. Importance of the CH/n hydrogen bond.
Ab initio MO calculations were carried out to investigate the conformational preference of n-propyl halides, isobutyl halides, sec-butyl halides, and n-butyl halides. It has been found in most cases that the rotamer in which a methyl group is close to the halogen atom is favored. The distance between the halogen atom and one of the hydrogens in the interacting CH3 group has been shown, in every case, shorter than the van der Waals distance. NBO charges gave results consistent with this finding. We suggest that the CH/n hydrogen bond contributes in determining the conformation of these molecules.
[NEW] Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Ryuta Otaki, Kazuyoshi Ueda, Hiroko Suezawa, Yoji Umezawa, Motohiro Nishio, Carbohydr. Res. 2007, 342, 1202-1209: 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 energy of axial conformers is smaller than that of the corresponding equatorial conformers in every case when the 2-substituent Z is electron-withdrawing (OCH3, F, Cl, Br). The difference in Gibbs energy between the equatorial and axial conformers DGeq-ax increases from Z = OCH3 to F, Cl, and then to Br. In the axial conformers, the interatomic distance between Z and the axial C-H, separated by four covalent bonds, has been found to be appreciably shorter than the van der Waals distance, suggesting the importance of 5-member CH/n (CH/O or CH/halogen) hydrogen bond, in stabilizing these conformations. Natural bonding orbital (NBO) charges of the relevant atoms have been shown different between the conformers: more positive for H and more negative for C in the axial conformers than in the corresponding equatorial conformers. In view of the above findings, we suggest that the CH/n hydrogen bond plays an important role in stabilizing the axial conformation in 2-substituted oxanes and 1,3-dioxanes, and by implication, in the anomeric effect in carbohydrate chemistry.
Osamu Takahashi, Katsuyoshi Yamasaki, Yuji Kohno, Kazuyoshi Ueda, Hiroko Suezawa, Motohiro Nishio, Chem. Asian J. 2006, 1, 852-859: 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 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 = CH3, C2H5, i-C3H7, t-C4H9). In every case, one of the equatorial conformations has been shown the most stable. Conformers with the axial CHCH3COR group have also been shown to populate in an appreciable concentration. Short CH/C=O and CH/O=C distances have been disclosed in every stable conformation. The result has been interpreted on the ground of CH/pi (C=O) and CH/O hydrogen bonds, which stabilize the geometry of the molecule. The ratio of the diastereomeric secondary alcohols produced in the nucleophilic addition to cyclo-C6H11CHCH3-CO-R was estimated, on the ground of the conformer distribution. The calculated result was consistent with the experimental data reported by Felkin and associates: the gradual increase of the product ratio (major/minor) was followed by a drop at R = t-C4H9. The energy of the diastereomeric transition states in the addition of LiH to cyclo-C6H11CHCH3-CO-R was also calculated for R = CH3 and t-C4H9. The product ratio does not significantly differ from R = CH3 to t-C4H9 in the case of aliphatic ketones. This is compatible with the above result calculated on the ground of the conformer distribution. Thus, the mechanism of the p-facial selection can be explained in terms of a simple premise that the geometry of the transition-state resembles the ground-state conformation of the substrates and that the nucleophilic reagent approaches from the less hindered side of the carbonyl pi-face.
Yoji Umezawa, Motohiro Nishio, Biopolymers 2005, 79, 248-258: 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.
Hiroko Suezawa, Shinji Ishihara, Yoji Umezawa, Sei Tsuboyama, Motohiro Nishio: Eur. J. Org. Chem. 2004, 4816-4822, Aromatic CH/pi Hydrogen Bond as an Important Factor Deciding the Relative Stability of Diastereomeric Salts Relevant to Enantiomeric Resolution. A Crystallographic Database Study.
A systematic study was carried out to understand the principle underlying the process of enantiomeric resolution by the use of the Cambridge Structural Database. The crystal structures of fourteen pairs of diastereomeric salts, containing the mandelate anion, or its analogues, as the chiral acid component, were analyzed in the context of the aromatic CH/pi hydrogen bond. The mean aromatic C-H…pi distance parameters of the less-soluble salts are shorter than in the moresoluble ones. Also, the C-H-pi-ring access angle, on average, is more acute in the less-soluble salts than in the moresoluble ones. Nontrivial discrepancies, on the other hand, have been noted in case-by-case comparisons of the parameters of several pairs. It was concluded that the contribution from the aromatic CH/pi hydrogen bond should at least be taken into account when considering enantiomeric separation.
Osamu Takahashi, Ko Saito, Yuji Kohno, Hiroko Suezawa, Shinji Ishihara, Motohiro Nishio: Eur. J. Org. Chem. 2004, 2398-2403, The Conformation of Alkyl Benzyl Alcohols Studied by Ab Initio MO Calculations. Comparison with IR and NMR Spectral Data
Ab initio MO calculations were carried out for the conformation of a series of alkyl-substituted benzyl alcohols C6H5CH2CHOH-R (R = CH3, C2H5, iPr, tBu) at the MP2/6-311G(d,p)//MP2/6-31G(d) level. It has been found that the conformation where the OH group is gauche to the phenyl group is the most stable. The geometry where both the OH and R groups are close to phenyl is the second most stable. The finding has been interpreted on the ground of attractive OH/pi and CH/pi hydrogen bonds and repulsive van der Waals interaction between vicinal CH groups. NMR nuclear Overhauser effects, spin-coupling data, and IR spectral data are consistent with the conclusion from the MO method.
O. Takahashi, K. Saito, Y. Kohno, H. Suezawa, S. Ishihara, M. Nishio: New J. Chem. 2004, 28, 355-360, Origin of the diastereofacial selectivity in the nucleophilic addition to chiral acyclic ketones. An ab initio MO study.
Ab initio MO calculations were carried out, at the MP2/6-311G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy of alkyl 1-phenylethyl ketones C6H5CHCH3COR 1 (R = CH3, C2H5, i-C3H7, t-C4H9). Rotamers a and a' whereby R is synclinal to C6H5 and the benzylic methyl group is nearly eclipsed to C=O has been shown the most stable in every case. Rotamer a is stabilized by 5-member CH/pi hydrogen bond and is more abundant than a', which is stabilized by less effective 6-member CH/pi bond. The diastereomeric ratio of the product secondary alcohols in the nucleophilic addition to 1 was estimated on the basis of the ground-state rotamer distribution. The Gibbs energy of the diastereomeric transition states was also calculated for a model reaction (C6H5CHCH3COR + LiH) at the same level of approximation. The transition-state geometries leading to the predominant product are similar to those of the ground-state conformation. In geometries leading to the minor product, the relevant torsion angles are twisted to avoid unfavourable steric interactions. The short CH/pi and CH/O distances suggest that these weak hydrogen bonds are operating in stabilizing the transition structures. The above two methods gave results consistent with each other. The mechanism of 1,2-asymmetric induction can thus be explained on the basis of a simple premise that the geometry of the transition-state resembles the ground state conformation of the substrate and the nucleophilic reagent approaches from the less hindered side of the carbonyl pi-face.
H. Suezawa, T. Yoshida, S. Ishihara, Y. Umezawa, M. Nishio: CrystEngComm 2003, 5, 514-518: CH/pi Interactions as disclosed on the fullerene convex surface. A database study.
A systematic search in the Cambridge Structural Database has disclosed that many CH groups are involved in the interaction with the fullerene convex surface; aliphatic as well as aromatic CHs are concerned. CH/pi interactions in C60 fullerene and C60 fulleride inclusion compounds were surveyed and compared. The mean CH/C60 intermolecular distance has been shown to be shorter in the fulleride complexes than in the fullerene complexes. The face-to-face type interaction was also surveyed, programmatically. The present study has demonstrated that the CH/pi interaction plays a considerable part in fullerene supramolecular chemistry, together with the van der Waals interaction. The concept of the CH/pi interaction will be of help in designing fullerene- and nanotube-based materials and in exploring the electronic structure of nonclassical pi-systems.
H. Suezawa, S. Ishihara, O. Takahashi, K. Saito, Y. Kohno, M. Nishio, New J. Chem. 2003, 27, 1609-1613: The molecular structure of acyclic aralkyl compounds studied by a crystallographic database survey. Relevance of the intramolecular CH/pi hydrogen bond to conformation
A database study was carried out, by the use of the Cambridge Structural Database, to investigate the conformation of aralkyl compounds ArCH2XCH2Y 1 and ArCHCH3XCH 2 in crystals. The structure bearing R (R: any group) and Ar (Ar: aromatic group) in the syn relationship has often been found in these compounds. The proportion of crystal structures bearing R and Ar in the syn relationship relative to the anti conformation (rsyn/anti) varied from 0.55 for 1 to 3.68 for 2. The logarithm of rsyn/anti was plotted against the difference in Gibbs energy delta Gsyn-anti obtained by MO calculations, at the MP2/6-311G(d,p)//MP2/6-31G(d) level, of model compounds C6H5CH2XCH3 and C6H5CHCH3XCH3. A linear correlation has been shown between ln rsyn/anti and delta Gsyn-anti. The CH/pi interaction is suggested to operate in controlling the R/Ar-folded crystal structure of these aralkyl compounds.
O. Takahashi, K. Saito, Y. Kohno, H. Suezawa, S. Ishihara, M. Nishio, Bull. Chem. Soc. Jpn. 2003, 76, 2167-2173: The conformation of 1-alkyl-2-phenylethylpropan-1-ols studied by ab Iinitio MO calculations. Relevance of the CH/pi and OH/pi hydrogen bonds.
Ab initio MO calculations were carried out, at the MP2/6-311G(d,p)//MP2/6-31G(d) level, for the conformation of a series of diastereoisomers of 1-alkyl-2-phenylethylpropan-1-ols CH3CH(C6H5)CH(R)OH and 2-phenylalkanes CH3CH(C6H5)CH2R (R = CH3, C2H5, i-C3H7, t-C4H9). A rotamer where R is gauche to C6H5 and anti to the benzylic methyl group has been found the most populated. Distances between the CH and OH hydrogens and the phenyl group in the interacted rotamers have been found short. Distribution of the possible rotamers depends on the presence or absence of the OH group and the configuration of the alcohol diastereoisomers. The results are discussed in the context of weak attractive molecular forces, CH/pi, OH/pi, and CH/O hydrogen bonds, as well as the unfavorable steric effects occurring between R and Me and between vicinal CH groups.
O. Takahashi, Y. Gondoh, K. Saito, Y. Kohno, H. Suezawa, T. Yoshida, S. Ishihara, M. Nishio, New J. Chem. 2003, 27, 1639-1643: The alkyl/phenyl-folded conformation of alkyl 1-phenylethyl sulphides and sulphones as evidenced by ab initio MO calculations. Implication to the 1,2-asymmetric induction.
Ab initio MO calculations were carried out, at the MP2/6-311G(d,p)//MP2/6-31G(d) level, to investigate the conformational energy of alkyl 1-phenylethyl sulphides C6H5CHCH3SR and sulphones C6H5CHCH3SO2R (R = CH3, C2H5, i-C3H7, t-C4H9). In every case, a rotamer whereby the alkyl group (R) is synclinal to C6H5 (Ph) and antiperiplanar to the benzylic methyl group (Ph-C-S-R torsion angle phi ca. 60 deg) has been found the most stable. Interatomic H/Cipso distances at the stable geometries are found short. The results are interpreted in the context of the CH/pi hydrogen bond occurring between CHs in R and the pi-system of Ph. Implication of the above results to the stereochemical mechanism of the oxidation of sulphides to give diastereoisomeric sulphoxides was discussed. The mechanism of 1,2-asymmetric induction (Cram open-chain model) was suggested to be explained on the basis of a simple premise that the geometries of the transition state resemble those of the ground state conformation of reactants.
O. Takahashi, Y. Kohno, Y. Gondoh, K. Saito, M. Nishio, Chem. Eur. J. 2003, 9, 756-762: 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 C6H5CH2-X-R (X = O, CH2, CO, S, SO, SO2; R = CH3, C2H5, iC3H7, tC4H9) 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 of the phenyl ring is short. The computational results are consistent with experimental data from supersonic molecular jet spectroscopy on 3-n-propyltoluene and NMR and crystallographic data on structurally related ketones, sulfoxides, and sulfones. In view of this, the alkyl/phenyl-congested conformation of these compounds has been suggested to be a general phenomenon, rather than an exception. The attractive CH/pi interaction has been suggested to be a dominant factor in determining the conformation of simple aralkyl compounds.
O. Takahashi, Y. Kohno, Y. Gondoh, K. Saito, M. Nishio, Bull. Chem. Soc. Jpn. 2003, 76, 369-374: General preference for alkyl/phenyl folded conformations. Relevance of the CH/pi and CH/O interactions to stereochemistry as evidenced by ab Initio MO calculations.
Ab initio MO calculations were carried out, at the MP2/6-311G (d,p)//MP2/6-31G(d) level, to determine the conformational energy of alkyl 1-phenylethyl sulfoxides, CH3CH(C6H5)-S(O)-R (R = CH3, C2H5, i-C3H7, and t-C4H9). In every case, a geometry (rotamer a, R/C6H5 torsion angle ca. 60 deg) where the alkyl group (R) is gauche to the C6H5 (Ph) and anti to the benzylic methyl group (Me) has been found to be the most stable. Rotamer b (300 deg), where R is flanked by Me and Ph, has been shown the next most stable in every case except for t-butyl analogue with the threo configuration. The R/Ph anti conformation (rotamer c: 180 deg) has been found the least stable. Interatomic distances (CH/pi as well as CH/O) at the stable geometries are found to be very short. These results are interpreted in the context of the attractive CH/pi and CH/O hydrogen bonds and the unfavorable electrostatic interaction between the S-O dipole and the quadrupole of the phenyl group. In view of the above result and of previous findings, the alkyl/phenyl congested folded conformation of aralkyl compounds has been suggested to be a general phenomenon.
H. Suezawa, T. Yoshida, Y. Umezawa, S. Tsuboyama, M. Nishio, Eur. J. Inorg. Chem. 2002, 3148-3155: CH/pi interactions implicated in the crystal structure of transition metal compounds. A database study.
A statistical study was carried out to investigate the role of the CH/pi interaction in the crystal structure of transition metal compounds. Thus, short CH/pi distances were surveyed in crystal structures deposited in the Cambridge Structural Database. Among organometallic entries bearing C6 or C5 aromatic rings, a substantial part of the structures has been found to bear intermolecular CH/pi contacts shorter than the van der Waals distance. Further, in many structures has been found short intramolecular CH/pi contacts. Interligand and intraligand CH/pi interactions were also surveyed in coordination compounds bearing typical ligands 1,10-phenanthroline, 2,2'-bipyridine, and 2,2':6',2''-terpyridine, as well as triphenylphosphane complexes of ruthenium, rhenium, and rhodium. The results were discussed in the context of the CH/pi interaction in controlling the crystal packing and the molecular structure of transition metal compounds. The CH/pi-interacted compact structure is a general aspect in coordination and organometallic chemistry.
O. Takahashi, K. Yasunaga, Y. Gondoh, Y. Kohno, K. Saito, M. Nishio, Bull. Chem. Soc. Jpn. 2002, 75, 1777-1783: The conformation of 2-phenylpropionaldehyde and alkyl 1-phenylethyl ketones as evidenced by ab initio calculations. Relevance of the CH/pi and CH/O interactions in stereochemistry.
Ab initio MO calculations were carried out for the conformation of 2-phenylpropionaldehyde 1 and related ketones CH3CH(C6H5)-CO-R (R = CH3 2, C2H5 3, i-C3H7 4, and t-C4H9 5) at the MP2/6-311G(d,p)//MP2/6-31G(d,p) level. The conformation whereby the alkyl group R is synclinal to the phenyl group (rotamer a, C6H5-C-CO-R torsion angle phi 64-93゜) has been found to be the most stable. The second most favorable one has been shown to have R flanked by the benzylic methyl group and C6H5 (rotamer b: phi 282-297゜). Difference in the enthalpy between a and b has been calculated 1.58, 2.16, 2.19, 2.08, and 4.89 kcal mol-1, respectively, for 1, 2, 3, 4, and 5. The C6H5/R antiperiplanar conformation (rotamer c) has been shown to be the least stable for 1 (phi 171゜) and not at an energy minimum for 2-5. In rotamers a and b, short interatomic distances have been shown between one of the alkyl hydrogens and the phenyl group. In rotamer a, a short distance has been calculated between one of the hydrogens of the benzylic methyl group and the carbonyl oxygen. The ab initio results are compatible with those obtained by NMR measurements. Contribution of the CH/pi and CH/O interactions to the conformational equilibria has been invoked to accommodate the above results. Instability of rotamer c may be due to the unfavorable electrostatic interaction of the C=O dipole vs. the quadrupole of the phenyl group. Conformational energies of methyl formate 6, N-methylformamide 7, and propionaldehyde 8 were also calculated to examine the effect of the CH/O interaction in carbonyl compounds. The results are consistent with the notion that the CH/O interaction is important in stabilizing the CH3/O eclipsed conformation.
Y. Umezawa, M. Nishio, Nucleic Acids Res. 2002, 30, 2183-2192: Thymine-methyl/pi interaction implicated in the sequence-dependent deformability of DNA.
You can see the full content of the paper by visiting the following UTML.
http://nar.oupjournals.org/cgi/content/full/30/10/2183?ijkey=9BlkohEIvWVNc&keytype=ref&siteid=nar
The crystal structure of deoxy-oligonucleotides were retrieved from the Nucleic Acid Database (NDB) and analyzed with the use of our program CHPI. The structure of 5'-ApTpApT-3' has been shown stabilized by the 5-methyl group in the thymidine moiety that favourably interacts with the adenine pi-ring preceding it. H2' of the deoxyribose in adenine also interacts with the thymine ring next to it. Since a 5'-ApT-3' sequence is accompanied with another 5'-ApT-3' in the complementary strand, the interaction is duplicated, thus forming a 'twin A/T-Me interaction'. Coordinates of oligonucleotides with A-T rich sequences were retrieved and analyzed. In almost every case, the thymidine 5-methyl group favourably interacts with an adenine ring in the same strand. The structure of duplexes incorporating A-tracts was also analyzed. The 5-methyl group in the thymidine moiety has been found to interact favourably with the base pi-ring before it. Since an A-tract is lined with an oligo-T sequence in the complementary strand, a successive N/T-methyl stacking may contribute in making the A-tracts robust and straight. Possibility of the N/T-methyl and the twin A/T-methyl motif in the deformability of DNA has been suggested. The role of methyl groups in modified DNA has been discussed on a similar basis.
This paper is dedicated to the memory of the late Professor Max F. Perutz, the founder of structural biology.
O. Takahashi, Y. Kohno, S. Iwasaki, K. Saito, M. Iwaoka, S. Tomoda, Y. Umezawa, S. Tsuboyama, M. Nishio, Bull. Chem. Soc. Jpn. 2001, 74, 2421-2430: Hydrogen-Bond-Like Nature of the CH/pi Interaction as Evidenced by Crystallographic Database Analyses and ab initio Molecular Orbital Calculations.
Abstract: Spatial distribution of CH hydrogen atoms with reference to a six-membered carbon aromatic ring was analyzed in the crystal structures deposited in the Cambridge Structural Database (CSD). The crystal data showed the propensity that the CH hydrogen atoms lie above the center of the aromatic ring to form interatomic CH/pi contacts. Investigation of the effects of the CH proton acidity on the strength and the structure of the CH/pi interaction has demonstrated that the distance between the hydrogen atom and the pi plane (Dpln) decreases with increase of the CH proton acidity (Dpln: CCH3 = sp2-CH > sp-CH = Cl2CH2 > Cl3CH), and that the C-H/pi access angle (alpha) tends to approach 180 degree in the same order. Further, a negative correlation has been found between Dpln and alpha. The directional preferences are in accord with the property of conventional hydrogen bond, indicating a hydrogen-bond-like character of the CH/pi interaction. In order to elucidate the intrinsic nature of the CH/pi interaction, ab initio calculations [MP2/6-311++G(d,p)] were carried out for methane/benzene, ethylene/benzene, and acetylene/benzene complexes. Potential surfaces obtained for the three model supramolecules are consistent with the results from the CSD analyses.
H. Suezawa, T. Yoshida, M. Hirota, H. Takahashi, Y. Umezawa, K. Honda, S. Tsuboyama, M. Nishio, J. Chem. Soc., Perkin Trans. 2 2001, 2053-2058: The CH/pi interaction as an important factor in the crystal packing and in determining the structure of clathrates.
Abstract: Crystal structures in the Cambridge Structural Database (CSD) were examined to investigate the role of the CH/pi interaction in the crystal packing and the structure of clathrates. More than 77% of organic crystals have been found to bear CH/pi interatomic distances shorter than 0.305.nm. Database subsets were edited by monitoring the entire CSD with the structure of included solvents (CHCl3, CH2Cl2, MeNO2, MeCN, MeOH, Me2CO, DMSO, DMF, dioxane, benzene, toluene and p-xylene). A great many of examined compounds have been shown to bear short CH/pi distances among themselves and between the supramolecular components. A variety of different solvents (protic, dipolar aprotic as well as non-polar) has been found to be included by CH/pi interactions. The crystal structures were retrieved and examined in detail for clathrates of 1,1,6,6-tetraphenylhexa-2,4-diyne-1,6-diol and 1,1'-binaphthyl-2,2'-dicarboxylic acid in complexation with their specific guests. The results are discussed in the context of the CH/pi interaction in controlling the specific structure of supramolecular aggregates.
Y. Umezawa, M. Nishio, Bioorg. Med. Chem. 2000, 8, 2643-2650: CH/pi Interactions in the Crystal Structure of TATA-Box Binding Protein/DNA Complexes.
Abstract: Crystal structures of TATA box-binding proteins (TBP) of various sources bound to their promoter DNA (TATA box) were analyzed with use of our program CHPI. A number of short CH/Csp2 contacts have been unveiled in these complexes at the boundary of TBP and the TATA box minor groove. The result was discussed in the context of the CH/pi interaction. Thus the nature of nonpolar forces, reported in the past at the interface of the two components, has been attributed to the CH/pi interaction. Furthermore, many CH/pi contacts have been disclosed within the same strand of the promoter DNA. The structure of the TATA element, partially unwound and severely bent on complexation, seems to be stabilized by CH/pi interactions; H2' of the deoxyribose moiety and the methyl group in the thymine nucleotide play the primary role.
K. Kobayashi, H. Takahashi, M. Nishio, Y. Umezawa, K. Tsuboyama, S. Tsuboyama, Anal. Sci. 2000, 16, 1103-1104: Crystal Structures of (S)-alpha-Methyltyrosinato-(SSSR)-[(2R,5R,8R,11R)- 2,5,8,11-tetraethyl-1,4,7,10-tetraazacyclododecane]cobalt(III) Bromide Perchlorate Dihydrate.
Abstract: In the title compound have been found a number of interligand CH/pi and NH/pi interactions to maintain a folded structure of the coordination complex
M. Hirota, K. Sakakibara, H. Suezawa, T. Yuzuri, E. Ankai, M. Nishio, J. Phys. Org. Chem. 2000, 13, 620-623: Intramolecular CH/pi interaction. Substituent effect as a probe for hydrogen-bond-like character.
Abstract: The contribution of a charge-transfer terms to the CH/pi interaction is supported by ab initio calculations and experiments on the substituent effect. NOE is an effective tool to determine the CH-pi interacted folded conformers separately from the stretched conformer.
H. Suezawa, T. Hashimoto, K. Tsuchinaga, T. Yoshida, T. Yuzuri, K. Sakakibara, M. Hirota, M. Nishio, J. Chem. Soc., Perkin Trans. 2 2000, 1243-1249: Electronic substituent effect on intramolecular CH/pi interaction as evidenced by NOE experiments.
Abstract: In order to demonstrate the hydrogen bond-like-character of the CH/pi interaction, electronic substituent effect on the equilibria between the stretched and the folded conformers of series of compounds capable of forming CH/pi interactions were examined by measurements of NOE enhancements of 1H NMR signals. Nuclear Overhauser enhancement is shown to be useful to determine the abundance of the CH/pi proximate folded conformers. The Hammett plots of all series of the compounds capable of having CH/pi interaction gave negative rho values. Together with other substituent effects (effects of electronegative substituents, on the CH donor, of ring size, and of alpha-alkyl substituent), the involvement of delocalization interaction and the hydrogen bond-like-character of the CH/pi interaction were established.
H. Takahashi, S. Tsuboyama, Y. Umezawa, K. Honda, M. Nishio, Tetrahedron 2000, 56, 6185-6191: CH/pi interactions as demonstrated in the crystal structure of host/guest compounds. A database study.
Abstract: Crystal structures deposited in the Cambridge Structural Database (CSD) were examined, by use of our program CHPI, for several kinds of clathrates in order to know the role of the CH/pi interaction in host/guest chemistry. These include cyclodextrin complexes, calix[4]arene complexes, cryptophane complexes and pseudorotaxanes. A number of short CH/pi distances have been shown in the crystal structure of these compounds. The result was discussed in view of the role of the CH/pi interaction in controlling the specific structure of supramolecules.
Y. Umezawa, S. Tsuboyama, H. Takahashi, J. Uzawa, M. Nishio, Tetrahedron 1999, 55, 10047-10056: CH/pi Interaction in the Conformation of Organic Compounds. A Database Study.
Abstract: A study was carried out, with use of the Cambridge Structural Database, to examine the role of CH/pi interaction in the conformation of organic compounds. A number of short intramolecular CH/pi distances have been disclosed in the crystal structure of these compounds. The structure was inspected to know whether the crystal conformation is a consequence of the so-called packing forces, or the CH/pi interaction plays a role. The result has demonstrated that the CH/pi interaction plays an appreciable role in controlling the conformation of organic compounds.
This paper is dedicated to the memory of the late Professor Derek H. R. Barton, the founder of concept of conformation in organic chemistry.
Y. Umezawa, S. Tsuboyama, H. Takahashi, J. Uzawa, M. Nishio, Bioorg. Med. Chem. 1999, 7, 2021-2026: CH/pi Interaction in the Conformation of Peptides. A Database Study.
Abstract: A study was carried out, with use of the Cambridge Structural Database, to examine the role of the CH/pi interaction in the conformation of peptides. A number of short intramolecular CH/pi distances have been shown in the crystal structure of peptides bearing at least an aromatic residue in the sequence. The molecular structure in the crystal was inspected individually to know whether the conformation is merely a consequence of the so-called packing forces, or the CH/pi interaction plays a role. It has been demonstrated that the CH/pi interaction constitutes one of the key factors in controlling the conformation of peptides.
Y. Umezawa, M. Nishio, Bioorg. Med. Chem. 1998, 6, 2507-2515: CH/pi Interactions in the Crystal Structure of Class I MHC Antigens and Their Complexes with Peptides.
Abstract: The crystal structure of class I major histocompatibility complex antigens (MHC) bound to their specific ligand peptides were analyzed, in the context of the CH/pi interaction, with use of a computer program CHPI. A number of short CH/Csp2 distances have been shown at the boundary of the heavy chain and b2 microglobulin. These interactions are conserved between species, human versus murine. A number of contacts shorter than the conventional van der Waals distance have been disclosed between CH hydrogens and aromatic side-chain groups in the MHC/peptide complexes. The CH/pi interaction has been suggested to contribute to the specificity in the complex formation of class I MHC.
Y. Umezawa, S. Tsuboyama, K. Honda, J. Uzawa, M. Nishio, Bull. Chem. Soc. Jpn. 1998, 71, 1207-1213: CH/pi Interaction in the Crystal Structure of Organic Compounds. A Database Study.
Abstract: A study was carried out by use of the Cambridge Structural Database in order to obtain insight into the nature of the CH/pi interaction and to examine its role in the crystal packing. The proportion of organic molecules bearing at least a CH/pi interaction in their crystal structures has been found considerable. The CH hydrogen atoms tend to point toward the center of the aromatic ring. A number of short CH/pi distances have been shown in crystal structures of organic compounds. Moreover, the mean CH/pi distance decreases as the acidity of the CH group increases. These results suggest that the CH/pi interaction is not simply ascribed to the dispersion force but involves other types of interactions, which are orientation-dependent and effective at wider range. It was suggested that the CH/pi interaction constitutes one of the important factors in controlling the crystal packing of molecules.
Y. Umezawa, M. Nishio, Bioorg. Med. Chem. 1998, 6, 493-504: CH/pi Interactions in the Crystal Structure of Guanine-Nucleotide Binding Proteins, Src Homology-2 Domains and Human Growth Hormone in Complex with their Specific Ligands.
Abstract: Possibility has been examined for the role of CH/pi interaction, by use of a computer program, in crystallographic data of several guanine-nucleotide binding proteins, src homology-2 domains and human growth hormone complexed with their specific ligands. Short CH/pi contacts have been found in every case where cohesive forces are expected. Comparison of the structures of functionary related proteins has shown that mutation may occur but necessary CH/pi interactions are conserved. A considerable part of the non-polar interactions, broadly ascribed in the past to the van der Waals interaction (dispersion force) or the hydrophobic effect, has been suggested to be attributed to a more specific attractive force, the CH/pi interaction.
REVIEWS
M. Nishio, Weak Hydrogen Bonds in Encyclopedia of Supramolecular Chemistry, in the press, Eds. J. L. Atwood, J. W. Steed, Marcel Dekker Inc., 2004.
1. INTRODUCTION
2. DETECTION OF WEAK HYDROGEN BONDS
2.1 Spectroscopy
2.2 Crystallography
2.3 Database Analyses
2.4 Theoretical Calculation
3. HYDROGEN BONDS BETWEEN HARD ACIDS AND SOFT BASES
4. HYDROGEN BONDS BETWEEN SOFT ACIDS AND HARD BASES
5. HYDROGEN BONDS BETWEEN SOFT ACIDS AND SOFT BASES
6. SUMMARY AND PROSPECT
Tetrahedron Report No. 378 (dedicated to Professor Sir Derek Barton for his 77th year)
M. Nishio, Y. Umezawa, M. Hirota, Y. Takeuchi, Tetrahedron 1995, 51, 8665-8701: The CH/pi Interaction: Significance in Molecular Recognition.
1. Introduction
2. Characteristics of CH/pi Interaction
3. Intramolecular Interaction
4. CH/pi Interaction in Molecular Recognition
4.1. Selectivity in organic reactions
4.2. Inclusion complexes
4.3. Protein/ligand complexes
5. Conclusion
Tetrahedron Report No. 265 (dedicated to Professor Sir Derek Barton, on the occasion of his 70th birthday)
M. Nishio, M. Hirota, Tetrahedron 1989, 45, 7201-7245: CH/pi Interaction: Implications in Organic Chemistry .
1. Introduction
2. Preference of Folded Conformations in Certain Acyclic Molecules
2.1 Transition states of 1,2-asymmetric induction
2.2 Conformations of several sulphoxide diastereoisomers
2.3 Conformations of several alcohols and ketones
2.4 Conformations of several alkylbenzenes
2.5 Generality of folded conformations
3. The Presence and the Nature of the CH/pi Interaction
3.1 Comparison of LIS data with force-field results
3.2 Other circumstantial evidence
3.3 X-ray data
3.4 Evidence from infrared studies
3.5 Molecular orbital calculations
3.6 Nature of the CH/pi interaction
4. Implications in Organic Chemistry
4.1 Chemical consequences of the CH/pi interaction
4.2 Conformations and chiroptical properties of 1,3-cyclohexadienes
4.3 Conformations and chiroptical properties of cyclohexanoes
5. Conclusion
M. Nishio, Y. Umezawa, M. Hirota, Yuki Gosei Kagaku Kyokai Shi 1997, 55, 2-12: The CH/pi Interaction. Implications in Molecular Recognition. (in Japanese)
Abstract: The CH/pi interaction is a weak hydrogen bond occurring between CH groups and pi-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 pi-groups are arranged generally in chemical structures and have many chance to interact each other. Unlike ordinary hydrogen bondings, the CH/pi 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/pi interaction hypothesis.
M. Nishio, Y. Umezawa, M. Hirota, Yukagaku 1996, 45, 609-617: The CH/pi Interaction- Implications in Chemistry and Life Science. (in Japanese)
M. Nishio, Y. Umezawa, M. Hirota, Kagaku to Seibutsu 1995, 33, 311-318: CH/pi InteractionｪFAn Important Factor to Determine Protein Specificities. (in Japanese)
M. Nishio, Y. Umezawa, M. Hirota, Farumashia 1994, 30, 1154-1159: The CH/pi Interaction - An intermolecular force occurring between alkyl and pi-groups. Significance in Chemistry and Biochemistry. (in Japanese)
M. Hirota, M. Nishio, Kagaku 1991, 46, 592-595: The CH/pi Hypothesis. Phenyl and t-butyl groups come close to each other. (in Japanese)
M. Nishio, Kagaku no Ryoiki 1983, 37, 243-251: Weak Attractive Interactions and Properties of Molecules. (in Japanese)
M. Nishio, Kagaku no Ryoiki 1979, 33, 422-432: CH/pi Hypothesis and Weak Chemical Interactions. (in Japanese)
M. Nishio, Kagaku no Ryoiki 1977, 31, 834-841, 998-1006: Stereochemistry and Interactions between Groups - Conformation and Reaction Specificity. (in Japanese)
BOOK
M. Nishio, Introduction to Intermolecular Forces in Organic Chemistry, Kodansha, Tokyo, 2000 (in Japanese)
M. Nishio, M. Hirota, Y. Umezawa, The CH/pi Interaction. Evidence, Nature, and Consequences, Wiley-VCH, New York, 1998
For further information, go to New book
S. Araki, T. Seki, K. Sakakibara, M. Hirota, Y. Kodama, M. Nishio, Tetrahedron: Asym. 1993, 4, 555-574: Effect of CH/pi Interaction on Chiroptical Properties of Olefins and Dienes. (dedicaed to the late Professor G. Snatzke)
H. Suezawa, A. Mori, M. Sato, R. Ehama, I. Akai, K. Sakakibara, M. Hirota, M. Nishio, Y. Kodama, J. Phys. Org. Chem. 1993, 6, 399-406: Evidence for the Presence of CH-pi Interacted ap-Conformers of Benzyl Formates.
S. Araki, K. Sakakibara, M. Hirota, M. Nishio, S. Tsuzuki, K. Tanabe, Tetrahedron Lett. 1991, 32, 6587-6590: Theoretical Study of CH-pi Interaction. Significant Enhancement of CD Spectra due to the Participation of CH/pi Interaction.
M. Karatsu, H. Suezawa, K. Abe, M. Hirota, M. Nishio, Bull. Chem. Soc. Jpn. 1986, 59, 3529-3534: Infrared C-D Stretching and 2H NMR Spectra of Isopropyl-2-d 1-(p-Substituted Phenyl)ethyl Ketones. Evidence for the Hydrogen Bond-Like Interaction between C-D Group and Aromatic pi-Electrons.
M. Hirota, T. Sekiya, K. Abe, H. Tashiro, M. Karatsu, M. Nishio, E. Osawa, Tetrahedron 1983, 39, 3091-3099: Theoretical Description of the Preference of Vicinal Alkyl/Phenyl gauche Conformation by Molecular Mechanics. An Alternative Interpretation for the CH-pi Attractive Interaction.
N. Kunieda, H. Endo, M. Hirota, Y. Kodama, M. Nishio, Bull. Chem. Soc. Jpn. 1983, 56, 3110-3117: The Conformational Analysis of 1-p-Tolyl-2-phenyl-1-pentanols, 1-p-Tolyl-2-phenylethanol, and 1-p-Tolyl-2-phenyl-1-propanone by Means of NMR Spectroscopy.
K. Kobayashi, Y. Kodama, M. Nishio, T. Sugawara, H. Iwamura, Bull. Chem. Soc. Jpn. 1982, 55, 3560-3564: The Conformation of Several 1-Phenylethyl and 1-Aryl Sulfoxides. Evidence for Attractive Aryl/Aryl Interaction.
S. Zushi, Y. Kodama, Y. Fukuda, K. Nishihata, M. Nishio, M. Hirota, J. Uzawa, Bull. Chem. Soc. Jpn. 1981, 54, 2113-2119: An Occurrence of Attractive Alkyl-Phenyl Interaction. The Conformations of Several 1-Phenyl-2-alkanols.
J. Uzawa, S. Zushi, Y. Kodama, Y. Fukuda, K. Nishihata, K. Umemura, M. Nishio, M. Hirota, Bull. Chem. Soc. Jpn. 1980, 53, 3623-3630: The Conformation of Several Aliphatic Alcohols. The General Occurrence of the Attractive Alkyl/Phenyl Interaction.
S. Zushi, Y. Kodama, K. Nishihata, K. Umemura, M. Nishio, J. Uzawa, M. Hirota, Bull. Chem. Soc. Jpn. 1980, 53, 3631-3640: The Conformations of 2-Phenylpropionaldehyde and Some Aliphatic Ketones. The Possible Importance of the CH/pi and CH/n Interactions in Determining the Molecular Geometry of a Mobile System.
Y. Kodama, S. Zushi, K. Nishihata, M. Nishio, J. Chem. Soc., Perkin Trans. 2 1980, 1306-1312: A General Preference for gauche Alkyl-Phenyl Interactions. The Use of Lanthanide Shift Reagents in determining the Preferred Conformations of Some Alkyl 1-Phenylethyl Sulphoxides.
Y. Kodama, K. Nishihata, S. Zushi, M. Nishio, J. Uzawa, K. Sakamoto, H. Iwamura, Bull. Chem. Soc. Jpn. 1979, 52, 2661-2669: The Conformation of a Diastereoisomeric Pair of 2,2-Dimethyl-4-phenyl-3-pentanols.
M. Hirota, Y. Takahashi, M. Nishio, K. Nishihata, Bull. Chem. Soc. Jpn. 1978, 51, 2358-2360: Conformational Analysis of Some Benzyl t-Butyl Sulfoxides by Measurement of Their Dipole Moments.
M. Nishio, 29th Symposium on Protein Structures, 1978, Osaka, Abstract, 161-164: CH/pi Interaction and the Structure of Protein. (in Japanese)
Y. Kodama, K. Nishihata, M. Nishio, N. Nakagawa, Tetrahedron Lett. 1977, 24, 2105-2108: Attractive Interaction between Aliphatic and Aromatic Systems.
Y. Kodama, K. Nishihata, M. Nishio, Y. Iitaka, J. Chem. Soc., Perkin Trans. 2 1976, 1490-1495: X-Ray Study of (aS,SS/aR,SR)-1-(p-Bromophenyl)ethyl t-Butyl Sulphoxide and Conformational Analysis of Diastereoisomeric Pairs of 1-Phenylethyl t-Butyl Sulphoxides.
Y. Iitaka, Y. Kodama, K. Nishihata, M. Nishio, Chem. Commun. 1974, 389-390: X-ray Structure Determination of 1-(p-Bromophenyl)ethyl t-Butyl Sulfoxide. Configuration and Conformation.
M. Nishio, Chem. Pharm. Bull. 1969, 17, 262-273: Nuclear Magnetic Resonance Studies of Sulfur Compounds. III. The Substituent and Solvent Effect on Magnetic Nonequivalence of the Methylene Protons of Phenyl Phenacyl and Phenyl Benzyl Sulfoxides.