Thermal properties of some small peptides (N-acetyl-amino acid-N′-methylamides) with non-polar side groups

• Tfus and ΔfusHm of methylamides of N-acetyl substituted non-polar amino acids were measured.
• Tfus and ΔfusHm increased as a function of the molar mass of the alkyl side chains.
• DL racemates showed Tfus of about 40 °C lower than those of the corresponding pure L enantiomers.
• Ideal solubility of solids at T = 298.15 K was estimated based on their Tfus and ΔfusSm.

Temperatures and molar enthalpies of fusion of a series of uncharged small peptides, namely the methylamides of N-acetyl substituted glycine, α-amino-butyric acid, alanine, valine, norvaline, leucine, isoleucine, norleucine, and proline, were measured by differential scanning calorimetry (d.s.c.), and molar entropies of fusion were derived. Both l- and dl-compunds were taken into account for the chiral molecules. No solid-to-solid transitions were detected from room temperature to fusion except for N-acetyl-N′-methyl alaninamide. Comparisons were made with the values for the N-acetyl amides of the corresponding amino acids previously reported. Both l enantiomers and dl racemates of α-aminobutyric acid, alanine, valine and isoleucine methylamides displayed temperatures of fusion sharply increasing as a function of molar mass, whereas much lower values, in countertendency with their molar mass increase, were found for proline and leucine methylamides. The racemic dl crystals showed temperatures of fusion of about 40 °C lower than those of the corresponding pure l enantiomers, except for proline and leucine derivatives. The enthalpies and entropies of fusion also varied as a function of molar mass following a similar trend with that of temperatures of fusion, except for alanine derivatives which showed lower values than expected. The values of ideal solubility of solids at T = 298.15 K were estimated based on their temperatures and molar entropies of fusion. Results were discussed with reference to the packing patterns based on hydrogen bonding and hydrophobic interactions.