The failure of simple empirical relationships to predict the viscosity of mixed aqueous solutions of guanidine hydrochloride and glucose has important implications for the study of protein folding

Viscosities of aqueous solutions of guanidine hydrochloride (GuHCl) were me asured in the presence of varying amounts of glucose. At high concentration s of glucose or GuHCl, the measured viscosities showed significant deviatio n from the values computed using a method proposed by Tanford (1966, J Biol Chem 241:3228-3232), This method was originally derived to allow the calcu lation of the effects of buffer or low concentrations of salts and other ad ditives on the density and viscosity of aqueous solutions of urea or GuHCl. Recently it has been used to estimate the viscosity of denaturant solution s that contain high concentrations of viscogens. Our results show that the extrapolation of this approach to solutions of highly concentrated viscous co-solutes leads to significant errors. The implications for experimental s tudies of the viscosity dependence of conformational transitions in protein s is discussed.