Binding of cyclic carboxylates to octa-acid deep-cavity cavitand

As part of the fourth statistical assessment of modeling of proteins and ligands (sampl.eyesopen.com) prediction challenge, the strength of association of nine guests ( 1 – 9 ) binding to octa-acid host was determined by a combination of 1 H NMR and isothermal titration calorimetry. Association constants in sodium tetraborate buffered (pH 9.2) aqueous solution ranged from 5.39 × 10 2 M −1 in the case of benzoate 1 , up to 3.82 × 10 5 M −1 for trans -4-methylcyclohexanoate 7 . Overall, the free energy difference between the free energies of complexation of these weakest and strongest binding guests was ΔΔG° = 3.88 kcal mol −1 . Based on a multitude of previous studies, the anticipated order of strength of binding was close to that which was actually obtained. However, the binding of guest 3 (4-ethylbenzoate) was considerably stronger than initially estimated.