Role of Hydrogen Bonding of Cyclodextrin–Drug Complexes Probed by Thermodiffusion

Niether, Doreen; Hovancová, Jana; Wiegand, Simone; Kita, Rio; Dhont, Jan K. G.; Eguchi, Kazuya; Kawaguchi, Tsubasa

doi:10.1021/acs.langmuir.7b02313

Journal Article

FZJ-2017-06811

Role of Hydrogen Bonding of Cyclodextrin–Drug Complexes Probed by Thermodiffusion

Niether, D.FZJ* ; Kawaguchi, T. ; Hovancová, J. ; Eguchi, K. ; Dhont, J. K. G.FZJ* ; Kita, R. ; Wiegand, S. (Corresponding author)FZJ*

2017
ACS Publ. Washington, DC

Langmuir 33(34), 8483 - 8492 (2017) [10.1021/acs.langmuir.7b02313]

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Please use a persistent id in citations: http://hdl.handle.net/2128/15461 doi:10.1021/acs.langmuir.7b02313

Abstract: The temperature-gradient induced migration of biomolecules, known as thermophoresis or thermodiffusion, changes upon ligand binding. In recent years, this effect has been used to determine protein-ligand binding constants. The mechanism through which thermodiffusive properties change when complexes are formed, however, is not understood. An important contribution to thermodiffusive properties originates from the thermal response of hydrogen bonds. Since there is a considerable difference between the degree of solvation of the protein-ligand complex and its isolated components, ligand-binding is accompanied by a significant change in hydration. The aim of the present work is therefore to investigate the role played by hydrogen bonding on the change in thermodiffusive behaviour upon ligand binding. As a model system we use cyclodextrins (CDs) and acetylsalicylic acid (ASA), where a quite significant change in hydration is expected, and where no conformational changes occur when a CD-ASA complex is formed in aqueous solution. Thermophoresis was investigated in a temperature range from 10 to 50°C by infrared thermal diffusion forced Rayleigh scattering (IR-TDFRS). NMR measurements were performed at 25°C to obtain information about the structure of the complexes. All CD-ASA complexes show a stronger affinity towards regions of lower temperature as compared to the free CDs. We found that the temperature sensitivity of thermophoresis correlates with the 1-octanol/water partition coefficient. This observation not only establishes the relation between thermodiffusion and the degree of hydrogen bonding, but also opens the possibility to relate thermodiffusive properties of complexes to their partition coefficient, which can not be determined otherwise. This concept is especially interesting for protein-ligand complexes where the protein undergoes a conformational change, different from the CD-ASA complexes, giving rise to additional changes in their hydrophilicity.

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