Tuning the Sign and Magnitude of Complexation-Induced pKa Shifts in Cucurbit[7]uril Host-Guest Complexes by Molecular Engineering

Cucurbiturils are popular macrocyclic receptors that bind complementary guest molecules with high affinity in aqueous environments. They are recognized for their ability to selectively bind positively charged guest molecules, including ionizable ammonium cations which frequently display much higher affinity than their neutral counterparts. This selectivity for the protonated species is translated into an increase in the basicity of encapsulated guests (i. e. into complexation-induced positive pK(a) shifts). However, despite being very rare, negative pK(a) shifts can be observed for specific guests. Following a previous work from our group reporting slightly negative pK(a )shifts for flavylium and chalcone dyes featuring N-diethylamino substituents (Delta pK(a)=- 0.2), herein we report a systematic study on the complexation of N-dialkylaminochalcones with CB7. The results show that the pK(a )shifts of these host-guest complexes can be rationally tuned by the nature of the N-dialkylamino groups and as well by target substitutions on the skeleton of the dye, allowing the design of a CB7 1 : 1 host-guest complex with a Delta pK(a)=- 0.6.