α-Aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2 (X = H, Br, MeO): Crystal structures, Hirshfeld surface analysis, computational studies and in silico molecular docking with the SARS-CoV-2 proteins

We report structural and computational studies of three α-aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2, namely diisopropyl((4-bromophenyl)(phenylamino)methyl)phosphonate (X = H, 1), diisopropyl((4-bromophenyl)((4-bromophenyl)amino)methyl)phosphonate (X = Br, 2) and diisopropyl((4-bromophenyl)((4-methoxyphenyl)amino)methyl)phosphonate (X = MeO, 3). The structures of 1–3 were fully confirmed by means of the 31P{1H} and 1H NMR spectroscopy. Crystal structures of 2 and 3 are isostructural and each contain two independent molecules in the asymmetric unit cell. Energy frameworks have been calculated to analyze the overall crystal packing of 1–3. The DFT calculations were performed to verify the structures of 1–3 as well as their electronic and optical properties. Molecular docking was applied to examine the influence of both the (S)- and (R)-enantiomers of 1–3 on a series of the SARS-CoV-2 proteins. We report structural and computational studies of three closely related α-aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2, namely diisopropyl((4-bromophenyl)(phenylamino)methyl)phosphonate (X = H, 1), diisopropyl((4-bromophenyl)((4-bromophenyl)amino)methyl)phosphonate (X = Br, 2) and diisopropyl((4-bromophenyl)((4-methoxyphenyl)amino)methyl)phosphonate (X = MeO, 3). The structures of 1–3 were fully confirmed by means of the 31P{1H} and 1H NMR spectroscopy. The geometrical parameters of all molecules are very similar. Two molecules in the crystal structures of 1–3 are interlinked through a pair of intermolecular N–H⋯O=P hydrogen bonds. Theoretical calculations based on density functional theory (DFT) were performed to verify the structures of 1–3 as well as their electronic and optical properties. The global chemical reactivity descriptors were estimated from the energy of the HOMO and LUMO. Molecular docking was applied to examine the influence of 1–3 on a series of the SARS-CoV-2 proteins. All the discussed aminophosphonates showed the best binding energies (−7.70 ÷ −8.00 kcal/mol) towards nonstructural protein 14 (nsp14 N7-MTase). [Display omitted] •We report α-aminophosphonates 4-XC6H4–NH–CH(4-BrC6H4)–P(O)(OiPr)2 (X = H, Br, MeO).•Crystal structures of α-aminophosphonates were studied by the Hirshfeld surface analysis.•DFT calculations were performed to verify the structures of α-aminophosphonates.•Molecular docking was used to probe α-aminophosphonates on the SARS-CoV-2 proteins.