[NEW] M. Nishio, Y Kohno, Chem-Bio Informatics Journal,2018, 18, 86-96: The Orbital-Effect-Myth
In the cyclohexane derivatives, the equatorial conformer, having less steric repulsion of hydrogen atoms adjacent to substituent, is dominant over the axial conformer. This is a normal stereochemical requirement. In hexose, containing oxygen atoms in the ring, however, α-anomer (with axial substituent) is more stable than β-anomer (with equatorial substituent) and it is called the anomeric effect. Why does this phenomenon, which is not compatible with the stereochemical intuition (but still widely accepted), happen at all? It has been more than 60 years since Edward reported it, but the root cause has not yet become clear. At present, the most popular explanation for the anomeric effect is that it is due to the interaction between a lone pair of electrons on oxygen and the anti-bonding orbital (σ*) of C-R bond. Contrary to popular belief, we demonstrate that this explanation does not hold.[NEW] M. Nishio, Chem-Bio Informatics Journal 2018, 18, 10-20: The Hydrogen Bond and its Surroundings Part 2. The Hydrophobic-Bond-Myth
The fashionable but stereotypic thinking on the concept of the so-called “hydrophobic bond” has been examined in light of criticisms raised by many scientists: Hildebrand, Shinoda, Israelachvili, and so on. The author’s comments are given on the harmful influence of the concept of “hydrophobic bond” in chemistry and biochemistry. In my opinion, this concept can be considered as a myth in modern science.[NEW] M. Nishio, Chem-Bio Informatics Journal 2017, 17, 85-92: Myths in Modern Science: The Hydrogen Bond and its Surroundings. Part 1. The Hydrogen-Bond-Myth
Widespread arguments of the hydrogen bond are criticized with respect to theories of protein folding and interactions of proteins with their specific ligands. Contrary to popular belief, by no means does the hydrogen bond play an important role in determining the conformation of proteins and the interactions of proteins with specific substrates. Stereotypical thinking on the hydrogen bond constitutes a myth in modern science and seriously restricts the success of structure-based drug design.Motohiro Nishio, Yoji Umezawa, Jacques Fantini, Manfred S. Weiss, Pinak Chakrabarti, Phys. Chem. Chem. Phys. 2014, 16, 12648-12683: CH–π hydrogen bonds in biological macromolecules.
This is a sequel to the previous Perspective ‘‘The CH–π hydrogen bond in chemistry. Conformation, supramolecules, optical resolution and interactions involving carbohydrates’’, which featured in a PCCP themed issue on ‘‘Weak Hydrogen Bonds – Strong Effects?’’: Phys. Chem. Chem. Phys. 2011, 13, 13873–13900. Evidence that weak hydrogen bonds play an enormously important role in chemistry and biochemistry has now accumulated to an extent that the rigid classical concept of hydrogen bonds formulated by Pauling needs to be seriously revised and extended. The concept of a more generalized hydrogen bond definition is indispensable for understanding the folding mechanisms of proteins. The CH–π hydrogen bond, a weak molecular force occurring between a soft acid CH and a soft base π- electron system, among all is one of the most important and plays a functional role in defining the conformation and stability of 3D structures as well as in many molecular recognition events. This concept is also valuable in structure-based drug design efforts. Despite their frequent occurrence in organic molecules and bio-molecules, the importance of CH–π hydrogen bonds is still largely unknown to many chemists and biochemists. Here we present a review that deals with the evidence, nature, characteristics and consequences of the CH–π hydrogen bond in biological macromolecules (proteins, nucleic acids, lipids and polysaccharides). It is hoped that the present Perspective will show the importance of CH–π hydrogen bonds and stimulate interest in the interactions of biological macromolecules, one of the most fascinating fields in bioorganic chemistry. Implication of this concept is enormous and valuable in the scientific community.Motohiro Nishio, Yoji Umezawa, Hiroko Suezawa, Sei Tsuboyama, The CH/pi Hydrogen Bond: Implication in Crystal Engineering. Implication in Crystal Engineering. Chapter 1 in The Importance of Pi-Interactions in Crystal Engineering: Frontiers in Crystal Engineering. Edited by Edward R. T. Tiekink and Julio Zukerman-Schpector. 2012 John Wiley & Sons, Ltd.
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
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)