Experimental and theoretical study of novel amino‐functionalized P(V) coordination compounds suggested as inhibitor of MProof SARS‐COV‐2 by molecular docking study

Abstract

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‐2Py]3 as ([Co(II){[O][NH‐2Py]P(O)[Ph]}2(DMF)2], 1) and ([Cu(II)Cl{[NH‐2Py]2P(O)[N‐2Py]}].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)Cl2(Pyrazole)4], 3) is also investigated. An evaluation of the inhibitory effect against the coronavirus (Main Protease [MPro] 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.