Metal complexes of thiosemicarbazones derived by 2-quinolones with Cu(I), Cu(II) and Ni(II); Identification by NMR, IR, ESI mass spectra and in silico approach as potential tools against SARS-CoV-2

Abstract

Substituted thiosemicarbazones derived by 2-quinolone were synthesized to investigate their complexation capability towards Cu(I), Cu(II) and Ni(II) salts. The structure of the complexes was established by ESI, IR and NMR spectra in addition to elemental analyses. Monodetate Cu(I) quinoloyl-substituted ligands were observed, whereas Ni(II) and Cu(II) formed bidentate-thiosemicarbazone derived by 2-quinolones. Subsequently, molecular docking was used to evaluate each analog's binding affinity as well as the inhibition constant (ki) to RdRp complex of SARS-CoV-2. Docking results supported the ability of the tested complexes that potentially inhibit the RdRp of SARSCov-2 show binding energy higher than their corresponding ligands. Additionally, ADMET prediction revealed that some compounds stratify to Lipinski's rule, indicating a good oral absorption, high bioavailability good permeability, and transport via biological membranes. Therefore, these metals-based complexes are suggested to be potentially good candidates as anti-covid agents.

Keywords: 2-Quinolones; Anti-Covid agents; Bidentate; Cu(I); ESI; Molecular docking; Monodentate; NMR; Ni (II) and Cu(II) salts; Thiosemicarbazones.

Graphical abstract

Scheme 1

Synthesis of 2-quinlonylthiosemicarbazones 3a-f.

Scheme 2

Synthesis of 2-quinlonylthiosemicarbazones-Cu(I) complexes 5a-d.

Scheme 3

Synthesis of 2-quinlonylthiosemicarbazones-Ni (II) and Cu (II) complexes 7a-h.

Fig. 1

Positive exact masses and isotope pattern, both experimentally and simulated mass spectra of the metal complex 5a formed between 3a and Cu(I)I.

Fig. 2

Positive exact masses and isotope pattern, both experimentally and simulated mass spectra of the formed metal complex 5b formed between 3b and Cu(I)I.

Fig. 3

FAB mass spectrum of the formed metal complex 7c from 3c and NiCl_2..

Fig. 4

IR spectrum of complex 5a.

Fig. 5

IR spectrum of complex 7a.

Fig. 6

¹H NMR spectrum of Cu(I) metal complex 5a formed between 3a and Cu(I)I.

Fig. 7

¹³C NMR spectrum of Cu(I) metal complex 5a formed between 3a and Cu(I)I.

Fig. 8

Structure of acidic form of compound 5a as in 5a’.

Fig. 9

3D diagram of the molecular surface illustrating the binding modes of Cu(I)complex (5a), Ni(II) complex (7d), Cu(II) complex (7e) and the ligand (3c) (interacted with the active site of RdRp complex of SARS-CoV-2. (PDB ID: 6M71).