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

Abstract

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 peptide-derived structures, retrieved from the Cambridge Structure Database, providing a library of tetrazole-based H-bonding 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 π-stacking interactions. Synergy of π…π and X-Y…π (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.