Synthesis, structure, DFT study and molecular docking inspection of spirobi[hexahydropyrimidine]-diones derivative
Malahat Kurbanova, Suraj N. Mali, Fidan Zaur Gurbanova, Haya Yasin, Shailesh S. Gurav, Chin‐Hung Lai
Abstract
• Three-component condensation of benzaldehyde, acetone, and urea with H₂SO₄ catalysis forms spirobi[hexahidropyrimidine]-dione. • The compound's structure was confirmed via X-ray analysis, revealing key molecular features. • Quantum theory of atom-in-molecule and noncovalent interaction index analysis found no intramolecular hydrogen bonds. • The molecule contains four N H bonds and two C O groups, influencing its chemical behavior. • DFT-NBO analysis indicated strong orbital interactions between lone pairs on oxygen and the C N bond. It has been established that three-component condensation of benzaldehyde, acetone and urea catalyzed H 2 SO 4 leads to the formation of spirobi[hexahidropyrimidine]-dione derivatives. The structure of the synthesized compound has been proved by X-ray method. The results of the quantum theory of atom-in-molecule and noncovalent interaction index analysis showed no intramolecular hydrogen bonds in the molecule studied. However, it contains four N H bonds and two C O groups. Based on the result of the DFT-NBO analysis, it was the lone pairs of oxygen on the C O group which are forming strong orbital interactions with the antibonding orbital of the C N single bond. The molecular docking was performed to investigate potential binding interactions of the compound with four target proteins including 5I4T (HIV-1), 5R7Z, 6M71 and 6VYB (SARS-Cov-2). Additionally, in-silico drug-likeness and ADME studies suggested oral activity (violations ≤ 1) of scaffold and predicted to be actively effluxed by P-gp (PGP+).