A supramolecular self-assembly of peptide-derived compounds via 1,5-disubstituted tetrazole-based supramolecular synthons: An experimental and computational study

The tetrazole moiety is a versatile scaffold in medicinal chemistry due to its specific structure and essential roles in biosciences. Here, a supramolecular behavior of newly synthesized benzyl 2-[5-(benzyloxycarbonylaminomethyl)tetrazol-1-yl)-3-phenyl-propanoate, 1, was studied by single-crystal X-ray crystallography and computational techniques, and compared with 21 structurally diversified 1,5-disubsituted tetrazole-containing peptidederived structures, retrieved from the Cambridge Structure Database, providing a library of tetrazole-based Hbonding synthons reported for the first time. Hirshfeld surface analysis, followed by the enrichment ratios, demonstrates that the supramolecular assembly of this class of compounds was controlled mainly by O...H, N...H, C...H and pi-stacking interactions. Synergy of pi...pi and X-Y...pi (X=C, N; Y=H, F) inter-contacts leads to diverse supramolecular patterns. The 3D topologies of the supramolecular architectures were visualised via energy frameworks, revealing a high contribution of dispersion forces. Using a quantum-chemical treatment, the molecular electrostatic potential and the HOMO and LUMO levels designated the chemical activity and stability of the compound. The compilation of these findings provides valuable information that may eventually form the basis of the design of more effective therapeutic agents containing tetrazole motifs.

Automated summary

A supramolecular behavior of a newly synthesized compound and a library of tetrazole-based H-bonding synthons were studied by X-ray crystallography and computational techniques. The supramolecular assembly was controlled by various interactions, including O...H, N...H, C...H, and pi-stacking interactions. The 3D topologies of the supramolecular architectures were visualized and dispersion forces played a crucial role. Quantum-chemical treatment revealed the chemical activity and stability of the compound. These findings provide valuable information for the design of therapeutic agents containing tetrazole motifs.