Solvent site preferences in the crystal structures of L-leucyl-L-leucine alcohol (1:1) complexes

The dipeptide L-Leu-L-Leu forms isomorphous 1:1 solvates with ethanol, 1-propanol and 2-propanol, space group P2(1) with Z=4. The two peptide molecules in the asymmetric unit have different hydrogen bonding interactions as well as side chain and main chain conformations. This leaves two solvent pockets with slightly different environments. When mixtures of ethanol and either of the two propanols are used as precipitating agents, the propanol is selectively incorporated at both solvent sites. When a mixture of 1-propanol and 2-propanol is used, however, one site shows a preference for 1-propanol, while the other site shows a similar preference for 2-propanol. The structures of the L-Leu-L-Leu 1-propanol 2-propanol solvate is a rare example of a mixed solvate. The potential for using mixed solvents in crystallization experiments is discussed.