Exploiting the Role of Molecular Electrostatic Potential, Deformation Density, Topology, and Energetics in the Characterization of S•••N and Cl•••N Supramolecular Motifs in Crystalline Triazolothiadiazoles

A detailed analysis of the molecular and crystal packing of a series of pharmacetitically active triazolothiadiazole derivatives is reported. The most notable feature from the analysis of the supramolecular motifs is the presence of inversion dimers due to the formation of strong S center dot center dot center dot N chalcogen bonds. This has been unequivocally established via inputs from energy calculations from PIXEL, the topological analysis using the approach of QTAIM from AIMALL, an analysis of the molecular electrostatic potentials plotted on Hirshfeld surfaces, and the analysis of the 3D-deformation densities obtained using Crystal Explorer. The total interaction energy for this contact is in the range of 28-33 kJ/mol in the molecules under investigation, and the electrostatic (Coulombic + polarization) contribution toward the total stabilization energy is more than 70%, indicating that such interactions are principally electrostatic in origin. The results from the analysis of the molecular ESP depict that this interaction exists between a strongly electropositive sigma-hole On the sulfur atom and an electronegative region on the nitrogen. 3D-deformation density (DD) maps reveal the presence of a charge depletion (CD) region on the sulfur atom which is directed toward the charge concentration (CC) region on the nitrogen atom facilitating formation of such contacts in the crystal. These are further invesigated by QTAIM based calculations which establish the closed-shell nature of these contacts. The crystal packing is further stabilized by the presence of significantly important it it stacking interactions, wherein the interaction energies, calculated by the PIXEL method, reveal that some of these interactions in crystals have significant contributions from electrostatic components, with a lesser contribution from dispersion forces that normally dominate such interactions. The existence of a contribution of similar to 48% from electrostatics between stacked rings owing to their unique electroitatic complementarily is a rare supramolecular feature observed in crystal packing in these solids. In addition, the existence of C-H center dot center dot center dot O, C-H center dot center dot center dot N, C-H-F, and Cl center dot center dot center dot N interactions is also characterized by a significant electrostatic component in their formation in crystals of these compounds.