The flip-flop hydrogen bonding phenomenon

Abstract

In crystalline β-cyclodextrin undecahydrate (β-cyclodextrin · 11 H2O), flip-flop hydrogen bonds O-H⋯O-H⇋H-O⋯H-O have been detected by neutron diffraction studies. In this type of bond the directionality is inverted dynamically even in the crystalline state as could be shown by diffraction experiments carried out at 293 K and at 120 K. Molecular dynamics methods (MD) can be used to simulate the dynamics of molecular systems on a computer. In this paper, the atomic trajectories obtained by MD simulations, of β-cyclodextrin at 293 K and at 120 K and of α-cyclodextrin at 293 K, are analysed with respect to the occurrence of hydrogen bonds of flip-flop type. In all three simulations the hydrogen bonds with the highest percentage of occurrence correspond to the ones found in the neutron diffraction structure. In the simulation of crystalline β-cyclodextrin at 293 K over 19 ps, sixteen out of eighteen experimentally detected flip-flop bonds are reproduced. The other two hydrogen bonds are unidirectional, O-H⋯O, i.e. they have a lifetime larger than 19 ps. The four experimentally observed flip-flops at 120 K are not seen in a 20 ps MD simulation. For α-cyclodextrin a flip-flop hydrogen bond is predicted with low population, which may be observed experimentally. The good agreement between MD calculations and neutron diffraction studies suggests that the force field used in the simulations yields a good description of cyclodextrin crystal structure at room temperature, and even the energetically delicate dynamic hydrogen bond flip-flop phenomenon is satisfactorily reproduced.