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Journal ArticleDOI

Evidence for Resonance-Assisted Hydrogen Bonding from Crystal-Structure Correlations on the Enol Form of the β-Diketone Fragment

16 May 1989-ChemInform (John Wiley & Sons, Ltd)-Vol. 20, Iss: 20
About: This article is published in ChemInform.The article was published on 1989-05-16. It has received 58 citations till now. The article focuses on the topics: Enol & Resonance.
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Journal ArticleDOI
TL;DR: The results attest that the pK(a) slide rule provides a reliable solution for the long-standing problem of H-bond-strength prediction and represents an efficient and practical tool for making such predictions directly accessible to all scientists.
Abstract: Unlike normal chemical bonds, hydrogen bonds (H-bonds) characteristically feature binding energies and contact distances that do not simply depend on the donor (D) and acceptor (:A) nature. Instead, their chemical context can lead to large variations even for a same donor−acceptor couple. As a striking example, the weak HO−H···OH2 bond in neutral water changes, in acidic or basic medium, to the 6-fold stronger and 15% shorter [H2O···H···OH2]+ or [HO···H···OH]− bonds. This surprising behavior, sometimes called the H-bond puzzle, practically prevents prediction of H-bond strengths from the properties of the interacting molecules. Explaining this puzzle has been the main research interest of our laboratory in the last 20 years. Our first contribution was the proposal of RAHB (resonance-assisted H-bond), a new type of strong H-bond where donor and acceptor are linked by a short π-conjugated fragment. The RAHB discovery prompted new studies on strong H-bonds, finally leading to a general H-bond classification ...

596 citations

Journal ArticleDOI
TL;DR: It is found that changes in these properties depend on a subtle balance between the strength of the hydrogen bond interaction, geometry of the newly formed ring system, and the relative energies of the open and closed conformations in polar and unpolar environments.
Abstract: The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we derive propensities for intramolecular hydrogen bond formation of five- to eight-membered ring systems of relevance in drug discovery. A number of motifs, several of which are clearly underutilized in drug discovery, are analyzed in more detail by comparing small molecule and protein-ligand X-ray structures. To investigate effects on physicochemical properties, sets of closely related structures with and without the ability to form intramolecular hydrogen bonds were designed, synthesized, and characterized with respect to membrane permeability, water solubility, and lipophilicity. We find that changes in these properties depend on a subtle balance between the strength of the hydrogen bond interaction, geometry of the newly formed ring system, and the relative energies of the open and closed conformations in polar and unpolar environments. A number of general guidelines for medicinal chemists emerge from this study.

453 citations

Journal ArticleDOI
TL;DR: An overview of the early literature on hydrogen bonding in the solid state is given in this paper, where the structural characteristics and physical consequences of C-H···O bonds are described.
Abstract: An overview is given on C–H···O hydrogen bonding in the solid state. Following a short survey of the early literature, the general properties of C–H···O bonding are discussed. The structural characteristics and some physical consequences of C–H···O bonds are described. A number of special systems are discussed in greater detail; these include water acceptors, inclusion complexes, and some biological structures.

223 citations

Journal ArticleDOI
TL;DR: This Account briefly review and update the use of the method of isotopic perturbation to search for a symmetric, centered, or single-well-potential H-bond in solution, and shows previous evidence for "short, strong, low-barrier" H- bonds to be based on ambiguous comparisons.
Abstract: In a symmetric hydrogen bond (H-bond), the hydrogen atom is perfectly centered between the two donor atoms. The energy diagram for hydrogen motion is thus a single-well potential, rather than the double-well potential of a more typical H-bond, in which the hydrogen is covalently bonded to one atom and H-bonded to the other. Examples of symmetric H-bonds are often found in crystal structures, and they exhibit the distinctive feature of unusually short length: for example, the O−O distance in symmetric OHO H-bonds is found to be less than 2.5 A. In comparison, the O−O distance in a typical asymmetric H-bond, such as ROH···OR2, ranges from about 2.7 to 3.0 A. In this Account, we briefly review and update our use of the method of isotopic perturbation to search for a symmetric, centered, or single-well-potential H-bond in solution. Such low-barrier H-bonds are thought to be unusually strong, owing perhaps to the resonance stabilization of two identical resonance forms [A−H···B ↔ A···H−B]. This presumptive bon...

173 citations

Journal ArticleDOI
TL;DR: In this paper, the authors focus on the crystallographic research aimed at a better understanding of hydrogen bonds which has been published since January 1990, focusing on the first half of 1990.
Abstract: This article focusses on the crystallographic research aimed at a better understanding of hydrogen bonds which has been published since January 1990. In the interest of continuity, earlier work is quoted when it relates to that published during this period.

147 citations


Cites background or result from "Evidence for Resonance-Assisted Hyd..."

  • ...…-cooperativity involves the polarization of the relatively weak and essentially electrostatic hydrogen-bond interactions, the or RAHB cooperativity occurs with strong hydrogen bonds and is considered by Gilli et al. (1989, 1993a, 1993b) to involve a significant covalent, i.e. exchange, component....

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  • ...H bonds and multiple C:::: N or C:::: O covalent bonds (Gilli et al., 1989)....

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  • ...Similarly it was the work of Gilli et al. (1989; 1993a) on hydrogen bonding involving the O¼C–...

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  • ...Two types of cooperativity have been recognized: -cooperativity, where the hydrogen bonds are linked by covalent O–H bonds, and -cooperativity or Resonance Assisted Hydrogen Bonding* (RAHB), where the hydrogen bonds are linked by both X–H bonds and multiple C:::: N or C:::: O covalent bonds (Gilli et al., 1989)....

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