Dilution enthalpies of two pairs of alpha-amino acid enantiomers, namely L-proline vs D-proline, and L-hydroxyproline vs D-hydroxyproline, in water-rich regions of dimethyl formamide (DMF) + H2O and dimethylsulfoxide (DMSO) + H2O mixtures (mass fractions of cosolvents w(COS) = 0 to 0.30) have been determined respectively at 298.15 K by isothermal titration calorimetry (ITC). The successive values of dilution enthalpy obtained in a single run of ITC determination were used to calculate homochiral enthalpic pairwise interaction coefficients (h(xx)) at the corresponding composition of mixed solvents according to the McMillan-Mayer' statistical thermodynamic approach. The sign and magnitude of h(xx) were interpreted in terms of solute-solute interactions mediated by solvent and cosolvent molecules, and preferential configurations of homochiral pairwise interactions (L-L or D-D pairs) in aqueous solutions. The variations of h(xx) with w(COS) were considered to be dependent greatly on the competition equilibrium between hydrophobic and hydrophilic interactions, as well as the structural alteration of water caused by the two highly polar aprotic cosolvents (DMF and DMSO). Especially, it was found that when one of the two kinds of interactions (hydrophobic or hydrophilic interactions) preponderates over the other in solutions, enthalpic effect of homochiral pairwise interactions is always remarkable, and is characterized by a large absolute value of h(xx), positive or negative, which corresponds respectively to the prevailing interactions of hydrophobicity or hydrophilicity. Interestingly, it was also found that the h(xx) values of L-enantiomers are generally larger than those of D-enantiomers across the whole studied composition range of mixed solvents, i.e. vertical bar h(LL)vertical bar > vertical bar h(DD)vertical bar, which is defined as enthalpic discrimination effect and attributed to the influence of preferential configuration on homochiral pairwise interactions in aqueous solutions. (C) 2013 Elsevier Ltd. All rights reserved.