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