Solubility-dependent melting temperature depression of binary substrate mixtures: A model study

In formulating eutectic media, the role of solvent adjuvant is not well understood in depressing the melting temperature of a binary substrate mixture (TMB). Here, we demonstrated the effect of solubility on the depression of TMB by using combinatorial model mixtures of N-benzyloxycarbonyl-l-Asp (CBZ-l-Asp) with either an l-amino acid or a d-sugar in different solvent adjuvants. When CBZ-l-Asp was mixed with an individual l-amino acid at an equi-molar ratio, TMB values varied approximately from 34 to 113 °C according to the hydrophobicity of adjuvants. Similarly, CBZ-l-Asp/d-sugar mixtures showed large variations of TMB values approximately from 43 to 112 °C according to the hydrophobicity of adjuvants. In the water adjuvant, TMB values in both CBZ-l-Asp/l-amino acid and CBZ-l-Asp/d-sugar showed strong correlations with the water solubility of either l-amino acids or d-sugars. In contrast, the hydrophobicity of individual compounds did not show any correspondence with TMB depression. The peak height of X-ray diffractions in the mixture of either CBZ-l-Asp/l-Lys or CBZ-l-Asp/l-Tyr was significantly reduced only when either l-Lys or l-Tyr was soluble in the adjuvant. These results show that the solubilization of a substrate component to an adjuvant contributed to the TMB depression, which may be caused by the enhanced structural homogeneity of a binary mixture.