New pyrazole‐4‐carbothioamide‐based metal complexes: Synthesis, spectral characterization, computational, antimicrobial, and antitumor investigations

Abstract

A series of 5‐hydroxy‐4‐(N‐substituted carbothioamide) pyrazole derivatives (HL1–HL5) and their iron(III), nickel(II), and copper(II) complexes have been synthesized. Structural elucidations of the isolated ligands and their complexes are basically accomplished by FT‐IR, 1H NMR, 13C NMR, UV–Vis, ESR, MS, and thermogravimetric analysis (TGA). The analytical data propose the stoichiometries 1:3 (M:L) for Fe(III) and 2:3 for both Ni(II) and Cu(II) complexes. The spectral data substantiate the bidentate coordination mode for all ligands towards metal ions via S and O atoms of CS of the carbothioamide group at pyrazole‐C4 and OH group at C(5) where deprotonation occurs from the enolic tautomer on chelation. Likewise, bidentate pattern of a bridged acetate group is confirmed in the case of Ni(II) and Cu(II) complexes. The magnetic moment values validate high spin octahedral geometry for Fe(III) complexes whereas the diamagnetic feature of Ni(II) complexes is in conformity with the square planar symmetry of low spin state. ESR spectra of all Cu(II) complexes support their existence in distorted square planar geometry with a considerable electron exchange between two copper ion centers of dinuclear type. TGA and DTG analysis of six complexes display their considerable thermal stability. Besides, the in vitro biological screening effects of some selected compounds are tested against various human pathogen microorganisms. Among the ligands, HL5 exhibits the greatest antibacterial activity against two Gram‐positive species (Bacillus subtilis and Staphylococcus aureus) and one Gram‐negative (Proteus vulgaris) in comparison with gentamicin drug. Furthermore, IC50 values of [Cu2(L5)3(OAc)] complex reveal its significant anticancer activity against the three tumor cell lines HCT‐116, MCF‐7, and HepG‐2 compared with imatinib and cisplatin as positive controls. Finally, the optimized structures of all ligands and their molecular electrostatic potential surfaces are established by utilizing density functional theory (DFT).

One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein

“…Furthermore, the most active derivatives 3a , 4b , 4d , and 4e revealed a lower energy gap (ΔE) (4.03–4.26 eV) compared with chloroquine (ΔE) = 4.49 eV, and remdesivir (ΔE) = 4.83 eV, i.e., the synthesized derivatives displayed the most stable conformer as well as the most polarizable. Generally, the molecules with lower energy gaps required less excitation energy and could offer electrons to neighboring biological receptors and were predicted to have high biological potency as confirmed by the experimental results [ 34 ]. Moreover, the values of softness S = 0.469–0.495 eV −1 and hardness ɳ = 2.01–2.13 eV displayed superior activity and lower hardness for the most active derivatives 3a , 4b , 4d , and 4e in comparison to chloroquine ( S = 0.446 eV −1 and ɳ = 2.24 eV) and remdesivir ( S = 0.41 eV −1 and ɳ = 2.41 eV).…”

Synthesis, characterization, biological evaluation, and molecular docking approach of nickel (II) complexes containing O, N‐donor chelation pattern of sulfonamide‐based Schiff bases

“…Generally, small energy gap ΔE ( E LUMO ‐ E HOMO ) is taken as a good indicator for complexation ability with neighboring central metal ion having empty d‐orbital or biological receptor as well as softness and hence chemical reactivity. [ 19 ] Among the examined ligands, L 4 exhibits the smallest Δ E (3.70 eV) which points to an ease of electron transfer with Ni (II) d‐orbitals owing to its long‐conjugated system of three linked phenyl groups with several donor atoms such as oxygen, nitrogen, and sulfur (Figure 6). Also, the higher negative total energy ( E T ) of the complexes ( 2 ) and ( 4 ) compared to their free ligands (Table 3) implies the greater stability of the isolated complexes.…”

“…Besides, the minimal inhibitory concentration (MIC, μg/ml) was estimated by applying broth microdilution assay as previously depicted in a study conducted by our group. [ 19 ] Ampicillin, gentamycin, and amphotericin B were used as standard references for antibacterial and antifungal activities.…”

“…Generally, small energy gap ΔE (E LUMO -E HOMO ) is taken as a good indicator for complexation ability with neighboring central metal ion having empty d-orbital or biological receptor as well as softness and hence chemical reactivity. [19] Among the examined ligands, L 4 exhibits…”

Designing metal chelates of halogenated sulfonamide Schiff bases as potent nonplatinum anticancer drugs using spectroscopic, molecular docking and biological studies

“…All inhibition zone diameter values in mm were assessed in triplicates for the tested samples. Also, MIC (minimal inhibitory concentration in µg/ml) was determined by the serial dilution method as reported 32,33 . The activity of the tested compounds was compared to ketoconazole, gentamycin, and ampicillin as reference controls for antifungal and antibacterial potencies.…”