This paper reports a creative methodology that attempts an explaination of how a compound kept its potency against the development of resistance. Given the current status of drug resistance, the importance of this paper is obvious.

Among the strengths are that great care has been taken to ensure the integrity of the crystals. The crystal structure is of excellent quality. The MD simulations use well-known and compatible forcefields.

Some notable weaknesses are that the DFT calculations employ B3LYP, and old functional that tends to yield erroneous results for systems that hydrogen bond. The use of only four compounds to get the scaling factors for the IR frequency values seems adventurous. The basis set is not referenced.

Some unclear things: no solvent model is mentioned in the DFT calculations nor is explicitly mentioned that they were done in the gas phase. There is no description, or reference, for the home-made optical parametric amplifier, nor for the home-made ultrafast Ti:Sapphire amplifier. This casts a shadow over the reproducibility of the IR results. Addition of descriptions of both pieces of equipment would improve the reproducibility of the results by other researchers.

Since I am not an expert in 2D-IR, most of those results remain obscure to me. I will thus comment only a few general points: In figures 1 and 2 the relevant information has numerical form, obtained from fits to the data, so the relevant numbers are not obvious from the figures. It would help to somehow highlight or add the numbers to the figures. Figure 3 shows fits to an exponential decay, but no data on goodness of fit is provided. In particular, figures 3b and 3d seem very dispersed around the fit, but without information on goodness of fit, there is no way to know if this is really a problem. Addition of the information on goodness of fit would dissipate any doubts about the fits.

So, the paper addresses an important problem in a creative way, but the suggested corrections could make the paper more readable and more reproducible.