Requirement for Hydrogen-Bonding Cooperativity in Small Polyamides: A Combined VT-NMR and VT-IR Investigation

A study of intramolecular hydrogen bonding in chloroform for a small combinatorial library of nine triamides with varying connecting chain length has been completed. The starting materials for the triamides are three diacids (succinic, glutaric, and adipic acid) and three amino acids (glycine, beta-alanine, and gamma-aminobutyric acid). The preferences for the head-to-tail type of folding pattern are identified for the smaller triamides (1 and 4). The preference for the head-to-tail folding pattern can be explained by the energetic superiority of an optimal hydrogen bond geometry in which the NH---O bond angle is near linearity. The beta-alanine containing triamides 2, 5, and 8 are resistant to intramolecular hydrogen bonding, especially to nearest neighbor hydrogen bonding. At lower temperatures, triamides 2 and 5 exhibit a small population of head-to-tail type of folding, while triamide 8 shows a significant population of bifurcated conformation. Triamide 6, 7, and 9 prefer bicyclic structures involving nearest neighbor hydrogen bonding. A nine-membered ring is large enough to accommodate a near linear N-H--O bond angle. Entropic effects are probably responsible for the preference of the nine-membered ring over a 12- or a 14-membered ring. The enhancement of hydrogen bonding in triamide 9 is enormous, and both NHs have a very large temperature dependence of chemical shifts (-15 ppb/K and -13.3 ppb/K for the terminal and the internal NH protons, respectively). Using appropriate temperature-dependent lower and upper limits of chemical shifts, a van't Hoff analysis gives the hydrogen bond strength for the terminal NH (DeltaH = -3.1 +/- 0.5 kcal/mol) and for the internal NH (DeltaH = -2.8 +/- 0.5 kcal/mol). The increased hydrogen bond strength is taken as evidence for hydrogen-bonding cooperativity from the two mutually enhanced individual hydrogen bonds. A near linear NH--O bond angle is required for this effect.