Binding of aliphatic ketones to cyclodextrins in aqueous solution

Abstract

Dissociation constants (K_d) for the complexation of 22 simple ketones with α-, β- and hydroxypropyl-β- cyclodextrin (α-CD, β-CD, and HP-β-CD) in aqueous solution have been determined. For these constants, there are various correlation involving pK_d(=–log K_d) which have the form of linear free energy relationships. In particular, there are strong correlation between the pK_d values of ketones (RCOR′) and related secondary alcohols [RCH(OH)R′], including cases where R and R′ form a ring. As with other alkyl derivatives, pK_d values for alkan-2-ones and alkan-3-ones increase monotomcally with chain length, with slopes about 0.4, corresponding to Gibbs energy increments of ca. 2.3 kJ mol^–1 for each CH₂ group that is sequestered by the CD. The strengths of binding of linear derivatives to α-CD and β-CD correlate well, but bulky and cyclic ketones bind more weakly to α-CD, due to its smaller cavity. The pK_d values for complexation of 18 of the 22 ketones by HP-β-CD and β-CD are fairly close and linearly related with a slope of 0.96 ± 0.03. These data are a subset of a larger set for 68 aliphatic compounds for which the slope is 0.99 ± 0.02. Thus, the strength of binding of such aliphatics to HP-β-CD and β-CD is generally close, although the penetration of the CD cavity by the guests is not necessarily the same for these two CDs.