Effect of the N-Alkyl Side Chain on the Amide-Water Interactions

Amide-water interactions influence the structure and functions of amide-based systems, such as proteins and homopolymers. In particular, the N-alkylation of the amide unit appears to play a critical role in defining the interactions of the amide group. Previous studies have linked the thermal behavior of amide-based polymers to the nature of their N-alkyl side chain. However, the connection between the chemical structure of the N-alkyl and the hydration of the amide remains elusive. In this study, the solvation structure and dynamics of amides, having differing N-alkyl groups, are investigated using a combination of linear and nonlinear infrared spectroscopies and computational methods. Interestingly, the dynamics of the amide local environment do not slow down as the N-alkyl side chain becomes bulkier, but rather speeds up. Computational calculations confirm the hydration dynamics and assign the effect to smaller amplitude and faster rotations of the bulkier group. It is also observed experimentally that the hydrogen-bond making and breaking between water and the amide carbonyl do not directly relate to the size of the N-alkyl side chain. The bulkier N-isopropyl substituent presents significantly slower chemical exchange dynamics than smaller chains (ethyl and methyl), but the two small groups do not present a major difference. The hydrogen-bond making and breaking disparities and similarities among groups are well modeled by the theory demonstrating that the N-alkyl group affects the amide hydration structure and dynamics via a steric effect. In summary, the results presented here show that the size of the N-substituted alkyl group significantly influences the hydration dynamics of amides and stress the importance of considering this effect on much larger systems, such as polymers.