Experimental and theoretical study of novel amino-functionalized P(V) coordination compounds suggested as inhibitor of M Pro of SARS-COV-2 by molecular docking study.

Amino-functionalized P(V) derivatives providing both N - and O -donor modes have attracted interest owing to their potential to form interesting coordination assemblies with applications such as biological drugs. Novel coordination modes of two- and four-dentate tris (pyridin-2-yl)phosphoric triamide OP[NH- 2 Py] 3 as ([Co (II) {[O][NH- 2 Py]P(O)[Ph]} 2 (DMF) 2 ], 1 ) and ([Cu (II) Cl{[NH- 2 Py] 2 P(O)[N- 2 Py]}].DMF, 2 ) have been synthesized and structurally studied. The metal center environment is distorted octahedral for 1 and distorted square pyramidal for 2 . The crystal structure of a new complex of Cu (II) with a Cu[N] 4 [Cl] 2 environment ([Cu (II) Cl 2 (Pyrazole) 4 ], 3 ) is also investigated. An evaluation of the inhibitory effect against the coronavirus (Main Protease [M Pro ] of SARS-CoV-2) was carried out by a molecular docking study and illustrates that these compounds have a good interaction tendency with CoV-2, where 1 has the best binding affinity with the biological target comparable with other SARS-CoV-2 drugs. Moreover, theoretical QTAIM and natural bond orbital (NBO) calculations are used to evaluate the metal-oxygen/-nitrogen bonds suggesting that they are mainly electrostatic in nature with a slight covalent contribution. A molecular packing analysis using Hirshfeld surface (HS) analysis shows that N-H … O (in 1 and 2 ) and N-H … Cl (in 3 ) hydrogen bonds are the dominant interactions that contribute to the crystal packing cohesion. The semi-empirical PIXEL method indicates that the electrostatic and repulsion energy components in the structures of 1 and 2 and the dispersion and electrostatic components in that of 3 are the major contributors to the total lattice energy.