To investigate this possibility experimentally, we prepared structural variants of 1g designed to isolate its anion-and cation-binding domains (Fig. ). The simple anion-binding variant 11 was constructed by replacing the t-Leu-arylpyrrolidine moiety with a n-octyl group, and was found to be a strong inhibitor of dealkylation relative to the racemic background reaction (Fig. , left inset). The cation-binding variant 12 was synthesized by Smethylation of the thiourea, thereby removing the dual-HBD properties of the catalyst. Compound 12 also induced no rate acceleration compared to the background reaction. Combining 10 mol % each of anion-binding variant 11 and cation-binding variant 12 also did not result in rate acceleration compared to background. Taken together, these observations provide compelling evidence that the presence of both cation-and anion-binding domains as well as their precise relative spatial orientation as in 1g are necessary for catalysis.