Stability and geometry of hydrogen‐bonded complexes of peptides

Abstract

AbstractObservations of induced circular dichroism (CD) bands in chloroform solution demonstrate the formation of specific, asymmetric complexes of the aromatic ligands 2‐pyridone and 2,6‐dichlorobenzoic acid with cyclic dipeptides of the general formula cyclo(L‐Pro‐X). The induced CD changes sign with the configuration of X due to subtle influences of the side chain on the geometry of the complex. Computations of interaction energies suggest that a plausible model for the complex of an aromatic ligand with the ‐CONH‐ of the cis secondary amide is a nearly planar arrangement of six heavy atoms in a ring containing two hydrogen bonds. The observed CD is matched by that computed for a tilt of the aromatic ligand toward the side chain of X. Binding constants were determined from the induced CD as a function of ligand concentration. For dichlorobenzoic acid these are about 450m−1 for the secondary amide and 50m−1 for the tertiary amide. For pyridone the binding constant is about 45m−1 for either the secondary or tertiary amide. For comparison self‐dimerization constants determined by vapor‐pressure osmometry in chloroform solution at 25°C are 870, 350, 50, and 20m−1 for pyridone, benzoic acid, dichlorobenzoic acid, and cyclo(L‐Pro‐Gly), respectively.