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. 2022 Oct 3:13:982484.
doi: 10.3389/fphar.2022.982484. eCollection 2022.

Theoretical exploration on structures, bonding aspects and molecular docking of α-aminophosphonate ligated copper complexes against SARS-CoV-2 proteases

Oval Yadav  1 , Manjeet Kumar  1 , Himanshi Mittal  1 , Kiran Yadav  1 , Veronique Seidel  2 , Azaj Ansari  1
Affiliations

Theoretical exploration on structures, bonding aspects and molecular docking of α-aminophosphonate ligated copper complexes against SARS-CoV-2 proteases

Oval Yadav et al. Front Pharmacol. .

Abstract

Recent years have witnessed a growing interest in the biological activity of metal complexes of α-aminophosphonates. Here for the first time, a detailed DFT study on five α-aminophosphonate ligated mononuclear/dinuclear CuII complexes is reported using the dispersion corrected density functional (B3LYP-D2) method. The electronic structures spin densities, FMO analysis, energetic description of spin states, and theoretical reactivity behaviour using molecular electrostatic potential (MEP) maps of all five species are reported. All possible spin states of the dinuclear species were computed and their ground state S values were determined along with the computation of their magnetic coupling constants. NBO analysis was also performed to provide details on stabilization energies. A molecular docking study was performed for the five complexes against two SARS-CoV-2 coronavirus protein targets (PDB ID: 6LU7 and 7T9K). The docking results indicated that the mononuclear species had a higher binding affinity for the targets compared to the dinuclear species. Among the species investigated, species I showed the highest binding affinity with the SARS-CoV-2 Omicron protease. NPA charge analysis showed that the heteroatoms of model species III had a more nucleophilic nature. A comparative study was performed to observe any variations and/or correlations in properties among all species.

Keywords: DFT; MEP map; NBO; copper species; molecular docking.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
B3LYP-D2 (A) optimized structure of species I and its (B) spin density plot and (C) HOMO-LUMO gap; (D) optimized structure of species II and its (E) spin density plot and (F) HOMO-LUMO gap; (G) optimized structure of species III and its (H) spin density plot and (I) HOMO-LUMO gap. (Bond lengths are in Å).
FIGURE 2
FIGURE 2
B3LYP-D2 (A) optimized structure, (B) spin density plot and (C) HOMO-LUMO gap of the species 3 IV (Bond lengths are in Å).
FIGURE 3
FIGURE 3
B3LYP-D2 (A) optimized structure, (B) spin density plot and (C) HOMO-LUMO gap of the species 3 V (Bond lengths are in Å).
FIGURE 4
FIGURE 4
Computed molecular electrostatic potential maps (solid/transparent) of (A) species I, (B) species II, (C) species III, (D) species IV, (E) species V, and (F) Ligand.
FIGURE 5
FIGURE 5
Computed NBO plots of (A) species I, (B) species II and (C) species III.
FIGURE 6
FIGURE 6
Bar diagram representing the natural population analysis of species I.
FIGURE 7
FIGURE 7
Molecular docking study of species I with the SARS-CoV-2 Omicron variant protease (7T9K).
See this image and copyright information in PMC

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