The Info List - C–H···O Interaction

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In chemistry, a C–H···O interaction is occasionally described as a special type of weak hydrogen bond. These interactions frequently occur in the structures of important biomolecules like amino acids, proteins, sugars, DNA and RNA.[1][2] History[edit] The C–H···O interaction was discovered in 1937 by Samuel Glasstone. Glasstone studied properties of mixtures of acetone with different halogenated derivatives of hydrocarbons and realized that dipole moments of these mixtures differ from dipole moments of pure substances. He explained this by establishing the concept of C–H···O interactions. Properties[edit] Similar to hydrogen bonds, a C–H···O interaction involves interactions of dipoles and therefore has directionality.[3] The directionality of a C–H···O interaction is usually defined by the angle α between the С, Н and О atoms, and the distance d between the O and H atoms. In a С–Н···О interaction, the angle α is in the range between 90 and 180°, and the distance d is usually smaller than 3.2 Å.[4] In the case of aromatic C–H donors, C–H···O interactions are not linear due to influence of aromatic ring substituents near the interacting C-H group.[5][6] If aromatic molecules involved in С–Н···О interaction belong to the group of polycyclic aromatic hydrocarbons, strength of C–H···O interactions increases with the number of aromatic rings. [7] C–H···O interactions can be important in drug design, being present in structures of therapeutic proteins,[8][9] and nucleic acids.[10] O-H···C and N-H···C type interactions could also play a significant role and were first analyzed in 1993.[11] References[edit]

^ G. R. Desiraju, T. Steiner, The Weak Hydrogen Bond in Structural Chemistry
and Biology, 1999, OxfordUniversity Press, Oxford (1999). ^ M. S. Weiss, Trends Biochem. Sci., 2001, 26, 521. ^ T. Steiner, G. R. Desiraju, Chem. Commun., 1998, 891. ^ T. Steiner, CrystRev, 2003, 9, 2-3, 177. ^ D. Ž.Veljković, G. V. Janjić, S. D. Zarić, "Are C–H···O interactions linear? Case of aromatic CH donors.", CrystEngComm, 2011, 13, 5005. DOI: 10.1039/C1CE05065F ^ J. Lj. Dragelj, G. V. Janjić, D. Ž. Veljković and S. D. Zarić, "Crystallographic and ab initio Study of Pyridine CH/O Interactions. Linearity of the interactions and influence of pyridine classical hydrogen bonds", CrystEngComm, (2013), vol. 15, 10481. DOI: 10.1039/C3CE40759D ^ "Strong CH/O interactions between polycyclic aromatic hydrocarbons and water: Influence of aromatic system size". Journal of Molecular Graphics and Modelling. 80: 121–125. 2018-03-01. doi:10.1016/j.jmgm.2017.12.014. ISSN 1093-3263.  ^ K. Ramanathan, V. Shanthi, R. Sethumadhavan, Int J Pharm Pharm Sci, 2011, 3, 3, 324. ^ D. P. Malenov, G. V. Janjić, D. Ž. Veljković, S. D. Zarić, "Mutual influence of parallel, CH/O, OH/π and lone pair/π interactions in water/benzene/water system", Computational and Theoretical Chemistry, (2013), vol. 1018, 59 - 65. DOI: 10.1016/j.comptc.2013.05.030 ^ D. Ž Veljković, V. B Medakovic, J. M. Andric and S. D. Zaric, "C–H/O interactions of nucleic bases with water molecule. Crystallographic and quantum chemical study.", CrystEngComm, 2014., DOI: 10.1039/C4CE00595C ^ M.A. Viswamitra, R. Radhakrishnan, J. Bandekar, G. R. Desiraju, "Evidence for O-H···C and N-H···C hydrogen bonding in crystalline alkynes, alkenes, and aromatics", J. Am. Chem. Soc. 1993, 115, 4868-4869.DOI:10.1021/ja00064a055

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Chemical bonds

Intramolecular (strong)


By symmetry

Sigma (σ) Pi (π) Delta (δ) Phi (φ)

By multiplicity

1 (single) 2 (double) 3 (triple) 4 (quadruple) 5 (quintuple) 6 (sextuple)


Agostic Bent Coordinate (dipolar) Pi backbond Charge-shift

Hapticity Conjugation Hyperconjugation Antibonding


Electron deficiency

3c–2e 4c–2e




möbius super sigma homo bicyclo spiro σ-bishomo spherical Y-


Metal aromaticity


Intermolecular (weak)

van der Waals forces

London dispersion


Low-barrier Resonance-assisted Symmetric Dihydrogen bonds C–H···O interaction

Noncovalent other

Mechanical Halogen Chalcogen Aurophilicity Intercalation Stacking Cation–pi Anion–pi Salt bridge

Bond cleavage