Novel Co²⁺ and Cd²⁺ Complexes Derived From a New <i>N</i>‐Donor Pyridyl‐Functionalized Thiophosphoric Triamide Ligand: Structural Investigation, DNA/COVID‐19/Monkeypox Molecular Docking, and Biological Assays

ABSTRACT A thiophosphoric triamide (SPT) ligand P(S)[NH‐ 2 Py] 3 was synthesized and utilized as a ligand to make novel binuclear and mononuclear Co 2+ and Cd 2+ complexes. The compounds are the first examples of discrete chelate SPT complexes with a [N] 3 P(S)‐based backbone in which the SPT acts as a flexible tridentate N , N , N ‐donor or N , N , O ‐donor ligand. The metal cation features a hexacoordinate environment M(N) 3 (Cl) 3 /M(N) 4 (O) 2 adopting a distorted octahedral geometry. Hirshfeld surface analysis affirms that the pyridinyl nitrogen is a more dominant H‐bond acceptor than the thiophosphoryl sulfur atom. The inhibitory activity against the MDA‐MB‐231 cancer cell line in vitro indicated a good inhibitory effect for all compounds. The mononuclear Co 2+ complex showed a stronger inhibitory activity against cancer cells than other studied compounds with an IC50 of 62 ± 1.4 nM. Antioxidant and antihemolytic activity of the compounds showed appreciable performance with the highest activities for the Cd 2+ complex. A computational DNA binding study by molecular docking indicated a good affinity of the compounds with the DNA receptor by a mixed mode of interactions. Docking was also performed on SARS‐CoV‐2 and monkeypox (Mpox), resulting in binding energies (−5.5 to −8.9 kcal/mol) that are competitive with current effective drugs.