[NEW] M. Ozawa, T. Ozawa, M. Nishio, K. Ueda, Journal of Molecular Graphics and Modelling 2017, 75, 117–124: The role of CH/pi interactions in the high affinity binding of streptavidin and biotin.
O. Takahashi, Y. Kohno and M. Nishio, New J. Chem. 2013, 37, in press: Influence of the CH/pi hydrogen bond on the enhancement of circular dichroism (CD) amplitude of 5,7-diene steroids: ergosterol, lumisterol, pirocarciferol, isopirocarciferol and structurally related cyclohexadienes.
Rotational strengths were calculated, by the TD-DFT (time-dependent density functional theory) method, for a series of 5,7-diene steroids, ergosterol, lumisterol, pirocarciferol, isopirocarciferol, as well as structurally related compounds such as 2,4-cholestadiene and levopimaric acid. The results were discussed in the context of the CH/pi hydrogen bond; we suggest that the CH/pi hydrogen bond plays an important role in the enhancement of CD amplitude of cisoid dienes.O. Takahashi, Y. Kohno, K. Ueda and M. Nishio, New J. Chem. 2013, 37, 843-849. DOI: 10.1039/c3nj41148f : Influence of the CH/pi hydrogen bond on the enhancement of circular dichroism (CD) amplitude of 1,3-cyclohexadiene compounds.
Introduction of methyl group(s) at bridgehead carbons at positions 10 and 5 of steroidal 1,3-dienes has been known to influence the Cotton effect of the pi-pi* transition at ca. 260 nm. Thus the positive sign of the circular dichroism (CD) curve of 5alpha-estra-1,3-dien-17beta-ol becomes negative in 5alpha-androsta-1,3- dien-17beta-ol, even though the helical sense of the diene chromophore remains practically unchanged. In order to investigate the effect of methyl substitution on the CD of 1,3-diene steroids, we carried out time dependent density functional theory (TD-DFT) calculations at the M06-2X/6-311++G(d,p)//MP2/6-31G(d,p) level. It has been shown that replacement of the bridgehead hydrogen by a methyl group greatly influenced the sign and amplitude of CD spectra of the pi-pi* transition. We suggest that the change in the CD curves by methyl substitution originates from CH/pi hydrogen bonds between the diene pi-system and a CH3 group homoallylic to it.O. Takahashi, K. Yamasaki,Y. Kohno, K. Ueda and M. Nishio, RSC Advances 2012, 2, 10891-10898: Importance of the CH/pi hydrogen bond in the enhancement of CD amplitude of exomethylene steroids.
Introduction of an axial methyl group to a bridgehead carbon has been known to enhance the circular dichroism (CD) amplitude of exomethylene steroids such as 4- and 6-methylene-5a-estrane, at ca. 200 nm (pi/pi* transition). To investigate the effect of a methyl group on the rotational strength of these steroids, time-dependent density functional theory (DFT) calculations were carried out at the M06-2X/6-311++G(d,p)//MP2/6-31G(d,p) level. It has been shown that the replacement of the bridgehead hydrogen atom at position 10 of these steroids by a methyl group influenced the CD amplitude at the pi/pi* transition. Analysis of natural bonding orbital (NBO) charges of relevant atoms has provided data consistent with this finding. In view of this, we suggest that the enhancement of the CD amplitude by methyl substitution b to the carbon-carbon double bond originates from the CH/pi hydrogen bond occurring between CH groups and the pi-system.Motohiro Nishio, J. Mol. Struct. 2012, 1018, 2-7, http://dx.doi.org/10.1016/j.molstruc.2012.03.012: The CH/pi hydrogen bond: Implication in chemistry. (Proceeding to the international conference on hydrogen bonds, Goettingen Sept. 2011)
The CH/pi hydrogen bond is the weakest extreme of hydrogen bonds that occurs between a soft acid CH and a soft base p-system. Implication in chemistry of the CH/pi hydrogen bond includes issues of conformation, crystal packing, and specificity in host/guest complexes. The result obtained by analyzing the Cambridge Structural Database is reviewed. The peculiar axial preference of isopropyl group in alpha-phellandrene and folded conformation of levopimaric acid have been explained in terms of the CH/pi hydrogen bond, by high-level ab initio MO calculations. Implication of the CH/pi hydrogen bond in structural biology is also discussed, briefly.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.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.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.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.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.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.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.
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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 complexM. 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.H. Takahashi, Y. Umezawa, S. Tsuboyama, 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.