Probing Local Electrostatics of Glycine in Aqueous Solution by THz Spectroscopy

Abstract

Based upon precise terahertz (THz) measurements of the solvated amino acid glycine and accompanying ab‐initio molecular‐dynamics simulations, we show that the N‐C‐C‐O open/close mode at 315 cm−1 serves as a sensitive, label‐free probe for the local protonation of the amide group. Experimentally, we can show that this holds not only for glycine but also for diglycine and valine. The approach is more general, since the changes due to protonation result in intensity changes which can be probed by THz time domain (0–50 cm−1) as well as by precise THz‐FT spectroscopy (50–400 cm−1). A detailed analysis allows us to directly correlate the titration spectra with pKa values. This demonstrates the potential of THz spectroscopy to probe the charge state of a natural amino acid in water in a label‐free manner.

Spectroscopic Fingerprints of Cavity Formation and Solute Insertion as a Measure of Hydration Entropic Loss and Enthalpic Gain

“…This is consistent with a population increase in the hard‐librations and a loss in population of soft‐librations, as observed experimentally. We want to mention that a similar absorption increase in the THz spectra at frequencies >400 cm −1 has been previously reported for hydration water molecules as a result of strong interactions with ions or with polar groups of biomolecules [43–45] . In order to quantify this effect, we take the slope of the absorption increase in the 450–600 cm −1 region and we compare it for different alcohols in Figure 3C.…”

Local Mutations Can Serve as a Game Changer for Global Protein Solvent Interaction

“…The mutations introduced in MMP14-SIA induce changes in the surface electrostatic potential: the charge of six surface exposed groups (L117K, Q120D, A139E, E248G, V270R, E286 K; Table S1) is altered, the majority of which result in a more positively charged surface. The change of a charge, from i.e., negative to positive, as well as surface charge density is known to influence the organization of water molecules within the interfacial regime. − In a recent study, we could show that the THz absorption coefficient Δα provides a measure for local electrostatics of amino acids, with the positively charged state giving rise to an increased THz response . Considering the surface electrostatic potential of the three MMPs investigated here, the following trend of increasing positive potential is revealed: MMP14-WT < MMP9-WT < MMP14-SIA .…”

“… 49 − 51 In a recent study, we could show that the THz absorption coefficient Δα provides a measure for local electrostatics of amino acids, with the positively charged state giving rise to an increased THz response. 52 Considering the surface electrostatic potential of the three MMPs investigated here, the following trend of increasing positive potential is revealed: MMP14-WT < MMP9-WT < MMP14-SIA. 11 We note that this trend corresponds surprisingly well with the observed THz absorption coefficients in which the THz response becomes more positive in sign for a more positively charged surface distribution.…”

Molecular Fingerprints of Hydrophobicity at Aqueous Interfaces from Theory and Vibrational Spectroscopies

“…In the present study we provide a detailed characterization of the HB-network which is formed by water at a set of distinct “hydrophobic” environments, by combining density functional theory-based MD (DFT-MD) simulations with theoretical SFG and experimental/theoretical THz-IR vibrational spectroscopies. While SFG is a natural probe of the vibrational properties of buried interfaces, we complement it with THz-IR absorption spectroscopy, which has been proved to be an extremely sensitive technique to reveal the intermolecular dynamics of water. , The strength of the THz low-frequency spectroscopic fingerprints is that they can be directly related to the corresponding hydrogen bond network motifs close to hydrophilic and hydrophobic moieties. − …”