Transport of vibrational energy via linear alkyl molecular chains can occur efficiently and with a high speed. This study addresses the question of how such transport is changed if an amide group is incorporated in the middle of such chain. A set of four compounds, Amn-4, was synthesized such that an amide group is connected to two alkyl chains. The alkyl chain on one side of the amide, featuring 4, 7, 11, or 15 CH2 units, is terminated by an azido group, while the alkyl chain on another side is of fixed length with four methylene groups terminated with a methyl ester group. The energy transport in Amn-4 in CD3CN solution, measured by relaxation-assisted two-dimensional infrared spectroscopy, was initiated and recorded using various combinations of tags and reporters, which included N3 and CO stretching modes of the end groups and amide-I and amide-II modes at the amide. It was found that the transport initiated by the amide-I mode in the alkyl chain attached to CO side of the amide proceeds with a constant speed of 4.2 Å/ps, supported by the CH2 rocking band of the chain. The end group-to-end group energy transport times for compounds with uneven alkyl chain length fragments appears to be additive. The transport from either end group of the molecule started as ballistic transport. The passage through the amide was found to be governed by intramolecular vibrational relaxation steps. After it passed the amide group, the transport was found to occur with constant but different speeds, dependent on the passage direction. The transport toward the ester was found to occur with the speed of 4.2 Å/ps, similar to that for the amide-I mode initiation and supported by the CH2 rocking band. The transport toward the azido group occurred with the speed of 8.0 Å/ps, which matches the speed supported by the CC stretching band. The results suggest that, after the CO group initiation, the excess energy reaches the amide group ballistically, redistributes at the amide, and reforms a wavepacket, which propagates further with a high speed of 8 Å/ps. This observation opens opportunities of controlling the energy transport process in molecules by affecting the alien group via specific interactions, including hydrogen bonding.

The global burden of the SARS-CoV-2 pandemic is thought to result from a high viral transmission rate. Here, we consider mechanisms that influence host cell–virus binding between the SARS-CoV-2 spike glycoprotein (SPG) and the human angiotensin-converting enzyme 2 (ACE2) with a series of peptides designed to mimic key ACE2 hot spots through adopting a helical conformation analogous to the N-terminal α1 helix of ACE2, the region experimentally shown to bind to the SARS-CoV-2 receptor-binding domain (RBD). The approach examines putative structure/function relations by assessing SPG binding affinity with surface plasmon resonance (SPR). A cyclic peptide (c[KFNHEAEDLFEKLM]) was characterized in an α-helical conformation with micromolar affinity (KD = 500 µM) to the SPG. Thus, stabilizing the helical structure of the 14-mer through cyclization improves binding to SPG by an order of magnitude. In addition, end-group peptide analog modifications and residue substitutions mediate SPG binding, with net charge playing an apparent role. Therefore, we surveyed reported viral variants, and a correlation of increased positive charge with increased virulence lends support to the hypothesis that charge is relevant to enhanced viral fusion. Overall, the structure/function relationship informs the importance of conformation and charge for virus-binding analog design.