Different phosphoric triamide [HN]3-nP(O)[N]n (n=1, 2) skeletons lead to identical non-covalent interactions assemblies: X-ray crystallography investigation, Hirshfeld surface analysis and molecular docking study against SARS-CoV-2

d In this work, we describe the crystal structures of two new phosphoramides containing the same [(3-Cl)C6H4NH] P(O) = Y segment (Y[N(CH3)CH2C6H5] (2) (1) and Y[NC4H8O] (2) (2)) and an improved model of [C6H11(CH3)N]P(O) [NHC(CH3)(3)] (2) (compound 3). The structures are experimentally investigated by single crystal X-ray diffraction using two types of refinements with spherical (S) and aspherical (AS) [Hirshfeld atomic refinements (HARs)] form factors, FT-IR and H-1, C-13, P-31 NMR spectroscopy. A biological molecular docking investigation gives hints to suggest an appropriate inhibitory activity against M-Pro of SARS-COV-2 (6M03 and 6LU7) especially for 1 with a binding energy around 6 (6M03)/ 7 (6LU7) kcal/mol. In the present work, the docking simulations are carried out for the first time for three series of ligand (L)-protein (P) complexes: L (with S form)-P (6M03), L (with AS form)-P (6M03) and L (AS)-P (6M03-N, with hydrogen atoms at their theoretical neutron values), where the binding energies are approximately proved to be 0.8 kcal/mol lower for simulations with 6M03-N than those for 6M03. Moreover, the structural study illustrates that the hydrogen bond patterns of all three structures consist of one-dimensional zigzag chains formed by classical N-H center dot center dot center dot O hydrogen bond interactions. Further stabilization is provided by weak interactions such as C-H center dot center dot center dot Cl (for 1 and 2), Cl center dot center dot center dot p (for 1 and 2) and C-H center dot center dot center dot O (for 2 and 3). Furthermore, the intermolecular interactions are analyzed by three-dimensional (3D) Hirshfeld surfaces, 2D fingerprint plots and enrichment ratios. The favored contacts identified by Hirshfeld surface analysis are H center dot center dot center dot O/O center dot center dot center dot H interactions covering the N-H center dot center dot center dot O hydrogen bonds for all three structures. For 1 and 2, Cl center dot center dot center dot C/ C center dot center dot center dot Cl contacts covering Cl center dot center dot center dot pi interactions are recognized as the most enriched contacts.