Crystal structure, Hirshfeld surface and reactivity of novel ligand-L_AT1 derived from dehydroacetic acid: intermolecular interactions with SARS-Cov-2/main protease

Abstract

The crystals of new ligand, namely (3E)-6-methyl-3-{1-[(pyridin-3-ylmethyl) amino] ethylene}-2H-pyran-2, 4(3H)-dione) (L_AT1), were synthesized using the evaporation solution technique. Single-crystal X-ray diffraction and physico-chemical characterization (ATR, proton and carbon-13 NMR and UV-Visible) of L_AT1 were reported. In addition, Hirshfeld surface analysis (HSA) of the solid compound, structure optimization, Mulliken and NBO charges, global indices of reactivity, local reactivity descriptors and molecular electrostatic potential (MEP) of the ligand were investigated theoretically. XRD analysis showed that L_AT1 crystallizes in the triclinic space group P-1 and the structure was stabilized through hydrogen bonds. HAS revealed that H…H (46.5%) and O…H (25.7%) contacts are in control of crystal stacking. The energy gap (4.679 eV) and reactivity descriptors indicate the stability of L_AT1. The Mulliken and NBO charges showed that the protons have a positive charge and the heteroatoms exhibit negative charges. The Fukui function and MEP study revealed that the heteroatoms are the most reactive sites for an electophilic attack on the ligand. Molecular docking simulation shows that the significant binding affinity of L_AT1 with SARS-CoV-2/Mpro is due to the formation of high number of hydrogen bonds.

Keywords:

• Chemical reactivity (DFT)
• crystal structure
• dehydroacetic acid derivative
• Hirshfeld surface analysis
• interaction with SARS-Cov-2/Mpro

Acknowledgments

The authors sincerely acknowledge the MESRS Algerian Ministry and Directorate-General for Scientific Research and Technological Development (Algeria) for supporting the present work.

Disclosure statement

No potential conflict of interest was reported by the author(s).