The properties of the ternary systems N,N,N',N'-tetramethylurea - N-methylacetamide - water were investigated using Fourier-transform infrared spectroscopy (FTIR), volumetric and compression measurements. Densities and sound velocities were determined in order to obtain the apparent molar volumes (VΦ) and apparent molar isentropic compressions (▪S,Φ). These values were then extrapolated to infinite dilution. Additionally, interaction parameters were calculated from the McMillan-Mayer theory. The studies were conducted at 288.15, 298.15, and 308.15 K, at atmospheric pressure (0.1 MPa). The concentration ranges of N-methylacetamide were 2, 4, 6, and 8 moles per kilogram of pure water, and for N,N,N',N'-tetramethylurea from 0 to around 0.35 moles per kilogram of solvent. Discrete changes in isentropic compression were observed. This is the result of the alignment of plots of ▪S,Φ0 as a function of NMA concentration. The results for N,N,N',N'-tetramethylurea were compared with analogous data for the system containing n-butylurea, which is an isomeric compound but exhibits different hydration behaviour. Additionally, large volumetric interaction coefficients were observed, indicating strong interactions between urea derivatives and NMA. This suggests the possibility of strong interactions between protein destabilizers and the protein backbone, differing from those observed for protein structure stabilizers. The observation contributes to understanding the mechanism of osmolyte action and their influence on protein stability.
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