Hydrophobic `lock and key' recognition of N-4-nitrobenzoylamino acid by strychnine

Abstract

During racemic resolution of N-4-nitrobenzoyl-DL-amino acids (alanine, serine and aspartic acid) by a fractional crystallization of strychninium salts, crystals of both diastereomeric salts were grown, and the crystal structures of strychninium N-4-nitrobenzoyl-L-alaninate methanol disolvate (1a), strychninium N-4-nitrobenzoyl-D-alaninate dihydrate (1b), strychninium N-4-nitrobenzoyl-D-serinate dihydrate (2a), strychninium N-4-nitrobenzoyl-L-serinate methanol solvate hydrate (2b), strychninium hydrogen N-4-nitrobenzoyl-L-aspartate 3.75 hydrate (3a) and strychninium hydrogen N-4-nitrobenzoyl-D-aspartate 2.25 hydrate (3b) were determined. The strychninium cations form corrugated layers, which are separated by hydrogen-bonded anions and solvent molecules. Common features of the corrugated layers are deep hydrophobic grooves at their surfaces, which are occupied by the 4-nitrobenzoyl groups of suitable anions. The hydrophobic `lock and key' recognition of 4-nitrobenzoyl groups of amino acid derivatives in deep grooves of the strychnine self-assembly causes the resulting surface to have more hydrophilic properties, which are more appropriate for interactions in the hydrophilic environments from which strychninium salts were crystallized. In the crystal structure of (2a) and (3a), such hydrophobic `lock and key' recognition is responsible for the lack of N—H+...O− hydrogen bonds that are usually formed between the protonated tertiary amine N atom of the strychninium cation and the deprotonated carboxyl group of the resolved acid. In the crystal structure of (2a) and (3a), the protonated amine N atom is a donor of hydrogen bonds, while the hydroxyl group of the serine derivative and water molecules are their acceptors. In light of the hydrophobic recognition, chiral discrimination depends on the nature of the hydrogen-bond networks, which involve anions, solvent molecules and the protonated amine N atom of strychninium cations.