Introduction
The basic building blocks of protein and peptides are 20 genetically encoded amino acids. These amino acids show enormous diversity concerning solubility, hydrophobicity, acidity and solid-state aggregation due to variable side chains.1 The amino acids also assume a variety of ionization state and it is well-known that the zwitterionic form (protonated α-amino group and deprotonated α-carboxylic acid group) is found to be the most stable form in aqueous solution. Some of the amino acids display excellent non-linear optical properties and piezo- or ferroelectricity.2-5Crystal structures of 20 genetically encoded amino acids have been studied well to understand the hydrogen bonding, supramolecular self-association and polymorphism.6-9 To understand the molecular recognition process between protein-inhibitor/drug molecules and protein-protein molecules, structural studies have been carried out for different amino acids complexed with other amino acids or with other coformers.10
Owing to the above, various research groups explored the crystallization of different amino acids (L, D and DL amino acids) in the presence of various carboxylic acids such as mono-, di-, tri- or aromatic carboxylic acids etc. These complexes revealed the most common synthons, variability in the supramolecular assembly, effect of chirality on the ionization state and stoichiometry. The crystal structures of L and DL-lysine complexed with one of the dicarboxylic acids namely adipic acid have been reported and the structures reveals that the arrangement of molecular ions in the layer is profoundly different.11 In another study, crystal structures of L/DL-arginine and L/DL-lysine complexed with L/DL-tartaric acid were reported. The result suggests that the L-lysine prefers to form a complex with D-tartrate rather than L-tartrate.12 We also reported the crystal structure of glycine-phthalic acid (an aromatic dicarboxylic acid) has been studied to delineate hydrogen bonding interactions.13
In the present study, we obtained a crystalline complex of L-lysine with L-mandelic acid and the crystal structure has been elucidated. Mandelic acid is one of a number of the aromatic carboxylic acids and is known to be an antiseptic used in the treat of urinary tract infections.14 It also acts as a chiral intermediate for the synthesis of pharmaceutical agents, such as cephalosporins, vasodilator cyclandelate, hexamine mandelate and antispasmodic mandelic acid benzyl ester.15 Therefore, structural studies on amino acids with mandelic acid could act as a model system to understand the molecular recognition of a drug by the protein molecules. A Cambridge Structural Database (CSD version 5.40, November 2018) search was conducted for amino acid-mandelic acid complexes. This search indicated that mandelic acid complexed with four different amino acids, such as alanine, cysteine, phenylalanine and methionine. In (R )-methionine (R )-mandelic acid complex, the methionine exists in the cationic form (a proton transferred from a carboxylic acid of mandelic acid), a neutral mandelic acid and an anionic mandelate.16The mandelic molecules are self-assembled via O–H···O hydrogen bonding between hydroxy-carboxylate and hydroxy-hydroxy groups. The crystal structures of phenylalanine-mandelic acid complexes ((R )-phenylalanine (R )-mandelic acid, (R )-phenylalanine (S )-mandelic acid and (S )-phenylalanine (S )-mandelic acid) have been reported.17,18In all three cases, phenylalanine exists in the zwitterionic form and mandelic acid is in the neutral form. In the (S )-alanine (S )-mandelic acid complex, the amino acid exists in zwitterionic form and the mandelic acid is in the neutral form.19 The self-assembly of mandelic acid molecules are mediated by O–H···O hydrogen bonding between hydroxy-carboxylic groups. The crystal structure of the (S )-alanine (R )-mandelic acid hemihydrate complex has also been reported.20 The orientation of the O–H group of the carboxylic acid is different in the alanine-mandelic acid complexes. In the cysteine-mandelic acid complexes, the amino acid exists in the zwitterionic form and mandelic acid is in the neutral form.21
Herein, the energetics of non-covalent interactions present in the L-(S ) lysinium-L-(S )-mandelate complex is investigated in detail using different theoretical approaches such as Hirshfeld surface,22 2D fingerprint plots23 and Bader’s quantum theory of atoms-in-molecules (QTAIM) framework.24