π-π Noncovalent Interaction Involving 1,2,4-and 1,3,4-Oxadiazole Systems: The Combined Experimental, Theoretical, and Database Study

A series of N-pyridyl ureas bearing 1,2,4- (1a, 2a, and 3a) and 1,3,4-oxadiazole moiety (1b, 2b, 3b) was prepared and characterized by HRMS, H-1 and C-13 NMR spectroscopy, as well as X-ray diffraction. The inspection of the crystal structures of (1-3)a,b and the Hirshfeld surface analysis made possible the recognition of the (oxadiazole)center dot center dot center dot(pyridine) and (oxadiazole)center dot center dot center dot(oxadiazole) interactions. The presence of these interactions was confirmed theoretically by DFT calculations, including NCI analysis for experimentally determined crystal structures as well as QTAIM analysis for optimized equilibrium structures. The preformed database survey allowed the verification of additional examples of relevant (oxadiazole)center dot center dot center dot pi interactions both in Cambridge Structural Database and in Protein Data Bank, including the cocrystal of commercial anti-HIV drug Raltegravir.

Automated summary

A series of N-pyridyl ureas bearing 1,2,4- and 1,3,4-oxadiazole moieties were synthesized, characterized, and analyzed through crystallography, Hirshfeld surface analysis, DFT calculations, and database surveys to reveal the interactions between these compounds. The study not only confirmed the presence of specific interactions theoretically, but also identified similar examples in other databases, demonstrating the generality of the observed interactions.