Computational Study of the Formation of Short Centrosymmetric N–H···S Supramolecular Synthon and Related Weak Interactions in Crystalline 1,2,4-Triazoles

A comprehensive
analysis of the crystal packing and the energetic
features of a series of four biologically active molecules belonging
to the family of substituted 4-(benzylideneamino)-3-(4-fluoro-3-phenoxyphenyl)-1H-1,2,4-triazole-5-(4H)-thione derivatives
have been performed based on the molecular conformation and the supramolecular
packing. This involves the formation of a short centrosymmetric R22(8) N–H···S supramolecular synthon in the solid
state, including the presence of C–H···S, C–H···O,
C–H···N, C–H···F, C–H···Cl,
C–F···F–C, C–Cl···Cl–C,
and C–H···π intermolecular interactions
along with π–π stacking to evaluate the role of
noncovalent interactions in the crystal. The presence of such synthons
has a substantial contribution toward the interaction energy (−18
to −20 kcal/mol) as obtained from the PIXEL calculation, wherein
the Coulombic and polarization contribution are more significant than
the dispersion contribution. The geometrical characteristics of such
synthons favor short distance, and the population of related molecules
having these geometries is rare as has been obtained from the Cambridge
Structural Database (CSD). Furthermore, their interaction energies
have been compared with those present in our molecules in the solid
state. The topological characteristics of the N–H···S
supramolecular synthon, in addition to related weak interactions,
C–H···N, C–H···Cl, C–F···F–C,
and C–Cl···Cl–C, have been estimated
using the quantum theory of atoms in molecules (QTAIM). In addition,
an analysis of the Hirshfeld surface and associated fingerprint plots
of these four molecules also have provided a platform for the evaluation
of the contribution of different atom···atom contacts,
which contribute toward the packing of the molecules in solids.