Guanidinium Chloride Molecular Diffusion in Aqueous and Mixed Water−Ethanol Solutions

Abstract

Solutions containing guanidinium chloride (GdmCl), or equivalently guanidine hydrochloride (GdnHCl), are commonly used to denature macromolecules such as proteins and DNA in, for example, microfluidics studies of protein unfolding. To design and study such applications, it is necessary to know the diffusion coefficients for GdmCl in the solution. To this end, we use molecular dynamics simulations to calculate the diffusion coefficients of GdmCl in water and in water-ethanol solutions, for which no direct experimental measurements exist. The fully atomistic simulations show that the guandinium cation Gdm (+) diffusion decreases as the concentration of both Gdm (+) and ethanol in the solution increases. The simulations are validated against available literature data, both transformed measured viscosity values and computed diffusion coefficients, and we show that a prudent choice of water model, namely TIP4P-Ew, gives calculated diffusion coefficients in good agreement with the transformed measured viscosity values. The calculated Gdm (+) diffusion behavior is explained as a dynamic mixture of free cation, stacked cation, and ion-paired species in solution, with weighted contributions to Gdm (+) diffusion from the stacked and paired states helping explain measured viscosity data in terms of atom-scale dynamics.

Rigid Cations Induce Enhancement of Microheterogeneity and Exhibit Anomalous Ion Diffusion in Water–Ethanol Mixtures

“…We have recently studied the linear molecules, carbon monoxide, nitric oxide, and cyanide ion in a water–ethanol mixture. It was found that as the ethanol composition in the mixture increases, the translational diffusion coefficient of neutral molecules also increases, whereas that of the charged ion decreases. , Another important study in the ion–water–ethanol mixture was performed with guanidium chloride (GdmCl) by Gannon et al The fully atomistic simulations showed that with the increase in the concentration of ethanol and the cation Gdm + , the diffusion of the cation decreases . Tembe and co-workers, in their study of magnesium chloride in water–ethanol mixture, showed that with the increase in the ethanol mole fraction, the ion pairing becomes more favorable .…”

Stability of proteins encapsulated in Michael‐type addition polyethylene glycol hydrogels

“…Likewise, convective and diffusive mass transfer should be reduced in a hydrogel compared to the crowding and free solutions, possibly slowing down dispersal of solutes. It was estimated that guanidinium would diffuse through the gel in 100 min, assuming 1D Fickian diffusion through a 2.2‐mm thick gel, a diffusivity of 6.5 × 10 −6 cm 2 /s in water, and reduction in effective diffusivity of 40% in the hydrogel (Gannon et al, 2008; Zustiak, Boukari et al, 2010). However, the tertiary structure of lysozyme responds rapidly to changes in denaturant concentration (van den Berg et al, 1999), and we suggest that differences in exposure time had minimal impact on lysozyme unfolding as the experiment was conducted for 120 min while it should have taken approximately 100 min for an equilibrium concentration of GuSCN or acrylamide to be reached between the surrounding solution and the gel.…”

Quick Refolding of High-Concentration Proteins via Microchannel Dialysis

“…These data were used to determine the permeation coefficient P , which was calculated as 1.1 × 10 -10 m 2 /s. The diffusion coefficient in the solution was about 5 x 10 -10 m 2 /s (Gannon et al, 2008). After 1440 min the concentrations in the feed and permeation chambers became almost equal.…”

“…(2). Atomistic molecular dynamics simulations predicted that the diffusivity of GdnHCl depends on the concentration of GdnHCl; for example, diffusivity at 5 M GdnHCl is around one third of that at 1 M GdnHCl (Gannon, Larsson, Greer, & Thompson, 2008). The permeation coefficient, P , used for the microchannel design was modified accordingly.…”

“…After 1440 min the concentrations in the feed and permeation chambers became almost equal. As the diffusion coefficient of GdnHCl was reported to be concentration dependent, and that at 1 M was around three times that at 5 M (Gannon et al, 2008), which is the concentration of feed used for the microchannel, P used for the microchannel design was collected with the scale factor.…”