Enthalpies for the two proton ionizations of the biochemical buffers N-tris(hydroxymethyl) methyl-4-aminobutanesulfonic acid (TABS), N-tris(hydroxymethyl)methyl-3-aminopropanesulfonic acid (TAPS) and 3-[N-tris(hydroxymethyl)methylamino]-2-hyroxypropane sulfonic acid (TAPSO) were obtained in water-methanol mixtures with methanol mole fraction (X-m) from 0 to 0.360. The ionization enthalpy for the first proton (Delta H-1) of all three buffers was small and exhibited slight changes upon methanol addition. The ionization enthalpy of the second proton (Delta H-2) of TABS increased from 39.6 to 49.8 kJ mol(-1) and for TAPS from 40.1 to 43.2 kJ mol(-1), with a minimum of 38.2 kJ mol(-1) at X-m = 0.059. For TAPSO the increase was from 33.1 to 35.6 kJ mol(-1) at X-m = 0.194, with measurements at higher X-m precluded by low solubility of TAPSO in methanol rich solvents. The solvent composition was selected so as to include the region of maximum structure enhancement of water by methanol. The results were interpreted in terms of solvent-solvent and solvent-solute interactions. (C) 2008 Elsevier B.V. All rights reserved.