More than 30 years ago, Nozaki and Tanford reported that the pK values for several amino acids and simple substances in 6 M guanidinium chloride differed little from the corresponding values in low salt (Nozaki, Y., and C. Tanford. 1967. J. Am. Chem. Soc. 89:736-742). This puzzling and counter-intuitive result hinders attempts to understand and predict the proton uptake/release behavior of prot...