Comment on "Microhydration of Biomolecules: Revealing the Native Structures by Cold Ion IR Spectroscopy".

This Viewpoint presents a re-examination of the conclusions of a study reported in The Journal of Physical Chemistry Letters (Saparbaev, et al . 2021, 12, 907) that compared the structure of microsolvated ions formed by electrospray ionization to those formed in the gas-phase via a previously published cryogenic ion trap approach. We conducted additional experiments that clearly show that most of the observed differences in the IR spectra can be accounted for by considering the different spectroscopic action schemes used to obtain them. In particular, the presence of the D 2 -tag induces shifts in some of the N-H and O-H peaks which need to be carefully considered before comparing spectra. Once these spectral effects are taken into account, we show that both clustering approaches yield similar cluster structures for the small GlyH + (H 2 O) n species. Using unimolecular reaction rate theory, we also show that for the small complexes considered here, only the gas-phase equilibrium distribution of conformers should be expected in both experimental approaches. In addition, the barrier heights necessary to kinetically trap high-energy conformers at 298 K is explored using a series of model polyalanine chains.