Engineering Intramolecular Hydrogen Bond Networks to Access Ensembles of Conformational Isomers of 24-Atom Macrocycles: Computation Corroborates Assignments and Predicts Structure

Abstract Intramolecular hydrogen bond (IMHB) networks contribute to the shape and physical properties of macrocycles. Understanding and ultimately engineering these networks represents a challenge to the field, both experimentally and computationally. Here, 24-atom triazine macrocycles are used as a model system to probe how a competing IMHB network can influence ensemble populations. Substitution distant from the macrocycle backbone offers an opportunity for introducing a competitive hydrogen bond donor. In its absence, incorporating symmetric and unsymmetric 2° amines leads to one and three persistent conformational isomers, respectively. Incorporation of a 1° amine leads to a competing IMHB network. Five persistent conformational isomers are observed. Computation corroborates assignment of the known conformers and predicts the structure of the emergent isomer: An expanded hinge conformer joins the hinge and non-hinge shapes previously reported. Corroborating evidence comes from H/D exchange of a methylene group on the macrocycle backbone, allowing for interpretation of a critical region of the 1H NMR spectrum. This five-conformer ensemble appears to be independent of the 1° amine chosen based on evidence obtained from 13C NMR spectra.