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 c ombinatorial library of nine triamides with varying connecting chain l ength has been completed. The starting materials for the triamides are three diacids (succinic, glutaric, and adipic acid) and three amino a cids (glycine, beta-alanine, and gamma-aminobutyric acid). The prefere nces for the head-to-tail type of folding pattern are identified for t he smaller triamides (1 and 4). The preference for the head-to-tail fo lding pattern can be explained by the energetic superiority of an opti mal hydrogen bond geometry in which the NH-O bond angle is near linear ity. The beta-alanine containing triamides 2, 5, and 8 are resistant t o intramolecular hydrogen bonding, especially to nearest neighbor hydr ogen 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 bondi ng. A nine-membered ring is large enough to accommodate a near linear N-H-O bond angle. Entropic effects are probably responsible for the pr eference of the nine-membered ring over a 12- or a 14-membered ring. T he 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, re spectively). Using appropriate temperature-dependent lower and upper l imits of chemical shifts, a van't Hoff analysis gives the hydrogen bon d strength for the terminal NH (Delta H = -3.1 +/- 0.5 kcal/mol) and f or the internal NH (Delta H = -2.8 +/- 0.5 kcal/mol). The increased hy drogen bond strength is taken as evidence for hydrogen-bonding coopera tivity from the two mutually enhanced individual hydrogen bonds. A nea r linear NH-O bond angle is required for this effect.