Determination of Binding Constants of Hydrogen-Bonded Complexes by ITC, NMR CIS, and NMR Diffusion Experiments

The host-guest complex formation between barbital and various acylaminopyridyl isophthalamides (Hamilton receptors) has been determined quantitatively. The syntheses of nine isophthalamides are described. Their structures differ in the substitution patterns on the central isophthalic unit, and the natures of the acyl residues. Ethylhexanoyl derivatives proved to be more soluble than pentanoyl amides. The association constants were determined by H-1 NMR titrations monitoring chemically induced shifts (CIS values), by H-1 NMR diffusion experiments, and by isothermal titration calorimetry (ITC), giving K-ass values in chloroform at 298 K between 33 x 10(3) and 100 x 10(3) M-1.