Complexation of uranyl (UO2)2+ with bidentate ligands: XRD, spectroscopic, computational, and biological studies

Abstract

Three new uranyl complexes [(UO2)(OAc)2(CMZ)], [(UO2)(OAc)2(MP)] and [(UO2)(OAc)2(SCZ)] were synthesized and characterized by elemental analysis, FT-IR, UV-Vis spectroscopy, powder XRD analysis, and molar conductivity. The IR analysis confirmed binding to the metal ion by the sulfur and ethoxy oxygen atoms in the carbimazole (CMZ) ligand, while in the 6-mercaptopurine (MP) ligand, the sulfur and the N7 nitrogen atom of a purine coordinated binding to the metal ion. The third ligand showed a 1:1 molar ratio and bound via sulfonamide oxygen and the nitrogen of the pyrimidine ring. Analysis of the synthesized complexes also showed that acetate groups had monodentate binding to the (UO22+). Density Functional Theory (DFT) calculations at the B3LYP level showed similar structures to the experimental results. Theoretical quantum parameters predicted the reactivity of the complexes in the order, [(UO2)(OAc)2(SCZ)] > [(UO2)(OAc)2(MP)]> [(UO2)(OAc)2(CMZ)]. DNA binding studies revealed that [(UO2)(OAc)2(SCZ)] and [(UO2)(OAc)2(CMZ)] have the highest binding constant (Kb) among the uranyl complexes. Additionally, strong binding of the MP and CMZ metal complexes to human serum albumin (HSA) were observed by both absorbance and fluorescence approaches. The antibacterial activity of the complexes was also evaluated against four bacterial strains: two gram-negative; Escherichia coli and Klebsiella pneumonia, and two gram-positive; Staphylococcus aureus and Streptococcus mutans. [(UO2)(OAc)2(MP)] had the greatest antibacterial activity against Klebsiella pneumonia, the gram-positive bacteria, with even higher activity than the standard antibiotic. In vitro cytotoxicity tests were also performed against three human cancer lines, and revealed the most cytotoxic complexes to be [(UO2)(OAc)2(SCZ)], which showed moderate activity against a colon cancer cell line. Thus, uranyl addition enhances the antibacterial and anticancer properties of the free ligands.

Theoretical Investigation by DFT and Molecular Docking of Synthesized Oxidovanadium(IV)-Based Imidazole Drug Complexes as Promising Anticancer Agents

“…The obtained values for the HOMO and LUMO for the metal complexes and the free organic molecules have been used to calculate the energy gap, E g = E LUMO − E HOMO . This indicator is usually used to assess the reactivity of the molecules [33]. A small E g value indicates the reactivity of the complexes through to the softness character, while the large energy gap between HOMO and LUMO complicates the transition of the electron, and we can express this as hard compounds.…”

“…Table 4 shows that the E g values were decreased after coordination to the metal ion, and CTNZ had the smallest value among the investigated compounds and was thus the most reactive molecule. For more details of the molecules' properties, we estimated the global reactivity descriptors, which are absolute electronegativities (χ), absolute hardness (η), chemical potentials (µ), global softness (S), and global electrophilicity (ω), using equations in our previous work [33] and illustrated in Table 4. The absolute softness is the reverse of the absolute hardness, which describes the sense to react with other molecules such as biological compounds, and we could arrange them according to the absolute softness (S) as follows: VO-CTNZ > VO-MNZ > VO-PNZ.…”

Biological efficacy of novel metal complexes of Nitazoxanide: Synthesis, characterization, anti-COVID-19, antioxidant, antibacterial and anticancer activity studies

“…The output files were visualized by Gauss View software and showed that the optimized geometries did not have an imaginary frequency, which confirmed that the structures were on the potential energy surface. Moreover, the HOMO and LUMO energies and orbital levels were extracted using Gauss View to calculate the following essential quantum parameters: energy gap (E gap = E LUMO − E HOMO ), absolute electronegativities (χ = −E HOMO +E LUMO /2), absolute hardness (ɳ = E LUMO − E HOMO /2), chemical potentials (μ = -χ), global softness (S = 1/2ɳ), and global electrophilicity (ω = π2/2ɳ) [18] .…”

“…The experiments employed a constant compound concentration and gradually increasing (1.57–5.15 μM) of Ct-DNA concentrations. The Ct-DNA was dissolved in a buffer solution (pH 7.4) and confirmed to be free of protein using the UV absorbance ratio (A 260 /A 280 ), which was in the range 1.8-1.9 [18] , [19] . The effective binding constants (K b ) were evaluated using the Benesi-Hildebrand equation …”

“…We used the Stern–Volmer equation to calculate the K SV , F o /F (or I 0 /I) = 1 + KSV [HSA], where F o is the fluorescence intensity in the absence of a quencher and F is the fluorescence intensity in the presence of metal complexes. K SV is the Stern–Volmer quenching constant obtained from the slope of the plot of F o /F [Complex] [18] , [21] .…”