Evidences for Cooperative Resonance-Assisted Hydrogen Bonds in Protein Secondary Structure Analogs

Cooperative behaviors of the hydrogen bonding networks in proteins have been discovered for a long time. The structural origin of this cooperativity, however, is still under debate. Here we report a new investigation combining excess infrared spectroscopy and density functional theory calculation on peptide analogs, represented by N-methylformamide (NMF) and N-methylacetamide (NMA). Interestingly, addition of the strong hydrogen bond acceptor, dimethyl sulfoxide, to the pure analogs caused opposite effects, namely red- and blue-shift of the N-H stretching infrared absorption in NMF and NMA, respectively. The contradiction can be reconciled by the marked lowering of the energy levels of the self-associates between NMA molecules due to a cooperative effect of the hydrogen bonds. On the contrary, NMF molecules cannot form long-chain cooperative hydrogen bonds because they tend to form dimers. Even more interestingly, we found excellent linear relationships between changes on bond orders of N-H/N-C/C = O and the hydrogen bond energy gains upon the formation of hydrogen bonding multimers in NMA, suggesting strongly that the cooperativity originates from resonance-assisted hydrogen bonds. Our findings provide insights on the structures of proteins and may also shed lights on the rational design of novel molecular recognition systems.