Collective hydration dynamics of guanidinium chloride solutions and its possible role in protein denaturation: a terahertz spectroscopic study

Abstract

The remarkable ability of guanidinium chloride (GdmCl) to denature proteins is a well studied yet controversial phenomenon; the exact molecular mechanism is still debatable, especially the role of hydration dynamics, which has been paid less attention. In the present contribution, we have addressed the issue of whether the collective hydrogen bond dynamics of water gets perturbed in the presence of GdmCl and its possible impact on the denaturation of a globular protein human serum albumin (HSA), using terahertz (THz) time domain spectroscopy (TTDS) in the frequency range of 0.3-2.0 THz. The collective hydrogen bond dynamics is determined by fitting the obtained complex dielectric response in a multiple Debye relaxation model. To compare the results, the studies were extended to two more salts: tetramethylguanidinium chloride (TMGdmCl) and sodium chloride (NaCl). It was concluded that the change in hydration dynamics plays a definite role in the protein denaturation process.

Nonmonotonic Hydration Behavior of Bovine Serum Albumin in Alcohol/Water Binary Mixtures: A Terahertz Spectroscopic Investigation

“…[48] All curves deviate strongly from linearity and show an unusual oscillating trend. To understandt he fluctuationsi t is important to consider that the overall hydration dynamics are ad elicate balance between competing interactions:a lco- hols preferentially solvate the protein surfacea nd deplete the hydration layer,w hich in turn increases the abundance of bulk water.C onsidering that the absorbances of hydrated and bulk water are different, [46,48] this factor leads to achange in Da. [48] Notably,t he oscillating feature is distinct for the different alcohols.…”

“…The frequency-dependent absorption coefficient [a(n)] in the THz region is correlated to the cooperative hydrogen-bonding dynamics of water,a si tm anifestst he density of states of molecules undergoing such motions. [46] The absorbance of water in this frequency region is very highr elative to that of other molecules, [22,51,52] and this provides au nique advantage to identify the changes in these parameters and to extract information on the alteration in the hydration dynamics.…”

“…For EtOH and 2-PrOH, the parameter oscillates between positive andn egative values of Da,w hereas for TBA,i ti sa lways negative. To understandt he fluctuationsi t is important to consider that the overall hydration dynamics are ad elicate balance between competing interactions:a lco- ChemPhysChem 2017, 18,749 -754 www.chemphyschem.org hols preferentially solvate the protein surfacea nd deplete the hydration layer,w hich in turn increases the abundance of bulk water.C onsidering that the absorbances of hydrated and bulk water are different, [46,48] this factor leads to achange in Da.…”

“…An alcohol-induced a helix to random coil transition of the protein secondary structure was revealed by circular dichroism spectroscopy measurements, and the effect was mostp rominent in TBA. [45][46][47] In this contribution, we aim to address the issue of how the addition of alcohols modulates the structure and the hydration of am odel protein. protein becomes destabilized and can even precipitate due to alcohol binding to the active sites of the proteins;a lso, during self-aggregation of the alcohols some protein molecules might become incorporated.…”

“…This technique has successfully been employed to extract hydration dynamics in both binary mixtures [22,25,44] and biomolecules. [45][46][47] In this contribution, we aim to address the issue of how the addition of alcohols modulates the structure and the hydration of am odel protein. The results could be helpful in pharmaceuticala pplications,a sa lcohols, in many cases, are used as solvents for various drugs, and knowledge of how biomolecules interactw ith alcohols serves as ap rerequisite for that.…”