The Effects of Buffers on the Thermodynamics and Kinetics of Binding between Positively-Charged Cyclodextrins and Phosphate Ester Guests

Article abstract of DOI:10.1021/jo991616d

Cyclodextrin derivatives in which the primary hydroxyl groups at the 6-positions of the sugar units have been replaced with 2-hydroxethylamino groups are known to bind phosphate esters with significant affinity. Association between the host and guest is mediated by a combination of hydrophobic and electrostatic interactions. Association constants for two cyclodextrin hosts with three phosphate ester guests are measured in a variety of buffer solutions, and it is found that the buffer has a large impact on the electrostatic component of the binding interaction. Negatively charged buffers such as phosphate and ADA (N-(2-acetamido)iminodiacetic acid) compete with the phosphate ester guests for binding to the positively charged cyclodextrins. This competition lowers the effective association constant between host and guest. Positively charged buffers such as Tris-HCl do not strongly compete and are thus more conducive to binding. The kinetics of dissociation of the host-guest complexes were measured in several buffers using ³¹P EXSY experiments. These measurements demonstrate that negatively charged buffers decrease the equilibrium constant by lowering the rate of association of these complexes but in most cases do not effect the dissociation rates.