Complexation Kinetics of Cyclodextrins with Bile Salt Anions: Energy Barriers for the Threading of Ionic Groups

Abstract

Binding constants for thousands of cyclodextrin complexes have been reported in the literature but much less is known about the kinetics of these host-guest complexes. In the present study, inclusion complexes of bile salts with β-cyclodextrin, γ-cyclodextrin and a methylated β-cyclodextrin were studied by NMR lineshape analysis to explore the structural factors that govern the complexation kinetics. For complexes with β-cyclodextrin, the association rate constants ranged from 2×10 6 to 2×10 7 M -1 s -1 while the dissociation rate constants ranged from 12 s -1 to 6000 s -1 at 25 °C. The kinetics were thus significantly slower than for any other β-cyclodextrin complex reported in the literature, due to the large energy barrier for threading the ionic sidechains of the bile salt anions.Bile salts with taurine and glycine sidechains had identical binding affinities but the kinetics differed by a factor of 10. Introduction of a single hydroxyl group at the binding site of the bile salts reduced the lifetimes and binding constants of the complexes more than 50 times. The strong temperature dependence of the rate constants revealed that the large activation energies were mainly enthalpic with a small contribution from entropy. The larger γ-cyclodextrin was threaded by the non-ionic end of the bile salts and the kinetics were too fast to be accurately determined. The study demonstrates that ionic groups on guest molecules constitute significant energy barriers for threading and dethreading of β-cyclodextrin hosts.

Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics

“… Host–guest k on (M −1 s −1 ) k off (s −1 ) K eq (M −1 ) CD–ADA short lifetime ~10 8 ~10 3 ~10 5 CD–CA long lifetime ~10 1 ~10 −3 ~10 4 Due to conjugation at the carboxylate end, the association and dissociation of CD–CA in our hydrogels can only occur through the steroid body side of CA. Kinetic constants for such association and dissociation were estimated from experimental values 55 and free energy calculations. Equilibrium constants ( K eq ) were obtained by Isothermal Titration Calorimetry (see Supplementary Information for details).…”

Quantitative Kinetic Modeling in Photoresponsive Supramolecular Chemistry: The Case of Water-Soluble Azobenzene/Cyclodextrin Complexes

“…However, the dynamics provided by the model and the extracted parameters were strictly identical whether we considered isomerization inside the CD cavity AZOt@βCD ⇆ AZOc@βCD or isomerization coupled to ejection AZOt@ βCD ⇆ AZOc + βCD. The complexation equilibria being fast, 26 they result in the same distribution of each species for both models.…”

Simultaneous analyte indicator binding assay (SBA) for the monitoring of reversible host–guest complexation kinetics

“…21 Besides, association rates play also a significant role in drug research due to their capability to modulate the onset of biological response. 22 In contrast to the large amount of biomedical related kinetic measurements, much less attention has been paid to the dynamics of host-guest complex formation of simple macrocyclic compounds [23][24][25][26] despite the increasing need for estimating the equilibration time or response time after an external stimulus, as are crucial for fine tuning in sensing, materials and drug delivery applications. 27 So far, rate constants of reversible encapsulation processes have been mainly studied via direct-binding assays (kinDBA) for environment-sensitive fluorescent guests by monitoring the alteration of their emission intensity upon host-receptor binding.…”