Letter | Published:

Flip-flop hydrogen bonding in a partially disordered system

Nature volume 296, pages 581583 (08 April 1982) | Download Citation



Cyclodextrins have proved useful as model systems for the study of hydrogen bonding1, α-Cyclodextrin (α-CD) crystal-lizes from water as a hexahydrate having well defined hydrogen bonds (O—H…O) in linear and circular arrangements favouring ‘endless’ …O—H…O—H…O—H… chains1–3. The larger β-cyclodextrin (β-CD) forms a crystalline dodecahydrate, β-CD·12H2O in which X-ray localization of the hydroxyl hydrogen atoms is made difficult because 25 of the 45 hydroxyl groups are statistically disordered and water molecules enclosed within the β-CD cavity are distributed over several sites that are not fully occupied4. We have therefore carried out a neutron diffraction study of β-CD at the Oak Ridge high flux isotope reactor to determine whether there is any well defined hydrogen bonding in disordered systems. In β-CD there are 19 hydrogen bonds of the type O—H…H—O. In these bonds, oxygen atoms are in the normal O—H…O distance range5, but two statistically half-occupied H atoms are arranged between them. The fact that the H…H separation of 1 Å is so short that the two H atoms positions are mutually exclusive suggests an equilibrium between two states: O—H…OO…H—O. Of the two H atoms only one is in hydrogen-bonding contact at a given time; the other one is flipped out to form a hydrogen bond with an adjacent acceptor group and vice versa. Because long hydrogen-bonding chains are involved in a cooperative, concerted motion (domino effect), we have coined the term ‘flip-flop hydrogen bond’. This study demonstrates that hydrogen bonds are opera-tive in disordered systems and display dynamics even in solid state.

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    • W. Saenger

    To whom correspondence should be addressed. Present address: Institut für Kristallographie, Freie Universität Berlin, Takustrasse 6, D-1000 Berlin 33, FRG.


  1. Abteilung Chemie, Max-Planck-Institut für experimentelle Medizin, D-3400 Göttingen, FRG

    • W. Saenger
    •  & Ch. Betzel
  2. Divisions of Biology and Chemistry, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830, USA

    • B. Hingerty
    •  & G. M. Brown


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