Substituent effect on intramolecular hydrogen bonding in β-amino acid-containing polyamides

An alkyl substitution in the beta-amino acid-containing polyamides 1, 2, and 3 leads to an increase in the population of intramolecularly hydrogen bonded conformations. However, the most stable conformation is not always the same one when the substituent is changed from a methyl group to an isopropyl group. For the beta-amino acid derivatives of succinic acid, a methyl group enhances the formation of a head-to-tail type of folding pattern through an 11-membered ring (2b), but an isopropyl group appears to decrease the enhancement. For beta-amino acid derivatives of glutaric acid, an isopropyl group promotes the formation of a bifurcated conformation (3c). The thermodynamic parameters for the equilibrium between non-hydrogen-bonded states and the head-to-tail type of folding of 2a and 2b are obtained by a van't Hoff analysis of the variable-temperature NMR data, which gives a Delta H Of -1.0 kcal/mol and a Delta S of -4.7 eu for triamide 2a and a Delta H of -1.0 kcal/mol and a Delta S of -3.7 e.u. for triamide 2b, each with a correlation coefficient of better than 0.99. The increased proportion of the intramolecular amide-amide hydrogen bond observed for triamide 2b is entirely due to entropic effects according to this analysis.