Inhibitory and Cooperative Effects Regulated by pH in Host-Guest Complexation between Cationic Pillar[5]arene and Reactive 2-Carboxyphthalanilic Acid

The study of host-guest complexation between reactive 2-carboxyphthalanilic acid (CPA) and two cationic pillararenes has been carried out. Host-guest complexation with significant kinetic effects was observed only with the smaller cavity size pillararene (P5A). Kinetics in the pH range 1.50-6.40, ESI-MS, H-1 NMR titration, and ROESY experiments were performed to characterize the complexes. High binding stoichiometry (H:G(2)) was observed for all CPA protonation states. The system is pH-dependent, and inversion of cooperativity (negative to positive) occurs by increasing the dianionic CPA(2-) concentration (allosteric behavior). Toward physiological pH, association constant K-1:1 does not change (10(4) M-1), and K-1:2 increased from 10(2) to 10(4) M-1, as well as the inhibitory effect increased up to 222-fold. NMR results elucidated the structure of the complex and allowed us to create a map of H-H interactions that describes well the diversity and number of interactions in the complex.