The synthesis, characterization, DNA/BSA/HSA interactions, molecular modeling, antibacterial properties, and in vitro cytotoxic activities of novel parent and niosome nano-encapsulated Ho(iii) complexes

Abstract

Based on the importance of metal-centered complexes that can interact with DNA, this research focused on the synthesis of a new Ho(iii) complex. This complex was isolated and characterized via elemental analysis, and FT-IR, fluorescence, and UV-vis spectroscopy. Additional confirmation of the Ho(iii) complex structure was obtained via single-crystal X-ray diffraction. DNA interaction studies were carried out via circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, viscosity measurements and emission spectroscopy; it was proposed that the metal complex acts as an effective DNA binder based on studies in the presence of fish DNA (FS-DNA), showing high binding affinity to DNA in the presence of hydrophobic and electron donating substituents. Also, the interactions of this complex with human (HSA) and bovine serum albumin (BSA) proteins were studied via fluorescence spectroscopy techniques and the obtained results reveal an excellent propensity for binding in both cases. Furthermore, the interactions of the Ho(iii) complex with DNA, BSA and HSA were confirmed via molecular docking analysis. The antimicrobial activities of the Ho(iii) complex were tested against Gram-negative bacteria and Gram-positive bacteria. In addition, a niosome nano-encapsulated Ho(iii) complex was synthesized, and the parent and encapsulated complexes were evaluated as potential antitumor candidates. The main structure of the Ho(iii) complex is maintained after encapsulation using niosome nanoparticles. The MTT method was used to assess the anticancer properties of the Ho(iii) complex and its encapsulated form toward human lung carcinoma and breast cancer cell lines. The anticancer activity in the encapsulated form was more than that of the parent Ho(iii) complex. In conclusion, these compounds could be considered as new antitumor candidates.

Fig. 1. (A) TEM and (B) SEM images of the niosome nano-encapsulated Ho(iii) complex (NN-En-Ho).

Fig. 2. An ORTEP view of the molecular structure of [Ho(bpy)(H₂O)₆]Cl₃ with ellipsoids drawn at the 50% probability level.

Fig. 3. The packing structure of [Ho(bpy)(H₂O)₆]Cl₃.

Fig. 4. UV-vis spectra of the Ho(iii) complex (Tris-buffer, pH 7.2) in the absence and presence of increasing amounts (1 is lowest and 6 is highest) of FS-DNA; DNA concentrations: 0, 1.1, 3.3, 5.5, 7.7 and 9.9 μM; inset: plot of [DNA]/(ε_a − ε_f) versus [DNA] during the titration of the complex with FS-DNA.

Fig. 5. The fluorescence spectra of complex–DNA; Ho(iii) complex concentration: 2.0 × 10⁻⁵ M in Tris-buffer at pH 7.2; DNA concentrations (1 is lowest, 16 is highest): 0, 1.1, 2.2, 3.3, 4.4, 5.5, 6.6, 7.7, 8.8, 9.9, 11.0, 12.1, 13.2, 14.3, 15.4 and 16.5 μM; inset: plot of log[DNA] vs. log(F₀ − F)/F.

Fig. 6. The emission spectra of the DNA–EB system in the presence of increasing amounts (1 is lowest, 11 is highest) of the Ho(iii) complex; inset: a plot of F/F₀versus [complex]/[DNA].

Fig. 7. (A) Stern–Volmer quenching plots of F₀/F versus [DNA] in the temperature range of 293–303 K. (B) The van't Hoff plot for the interaction of the Ho(iii) complex and DNA.

Fig. 8. CD spectra of (A) FS-DNA, (B) BSA and (C) HSA in the absence (solid line) and presence (dashed line) of the Ho(iii) complex.

Fig. 9. (A) The fluorescence spectra of BSA–Ho(iii) complex; BSA concentration: 3.6 × 10⁻⁶ M in Tris-buffer at pH 7.2; Ho(iii) complex (1 is lowest, 13 is highest): 0, 1.25, 2.51, 3.75, 5.0, 6.25, 7.5, 8.75, 11.25, 12.5, 13.75 and 16.25 μM; inset: plot of log[Ho(iii) complex] vs. log(F₀ − F)/F. (B) The fluorescent spectra of HSA–Ho(iii) complex; HSA concentration: 1.57 μM in Tris-buffer at pH 7.2; Ho(iii) complex (1 is lowest, 12 is highest): 0, 1.25, 2.51, 3.75, 5.0, 6.25, 7.5, 8.75, 11.25, 12.5, 13.75 and 15.0 μM; inset: plot of log[Ho(iii) complex] vs. log(F₀ − F)/F.

Fig. 10. (A) Stern–Volmer quenching plots of F₀/F versus [Ho(iii) complex] in the temperature range of 293–303 K. (B) The van't Hoff plot for the interaction of the Ho(iii) complex with BSA. (C) Stern–Volmer quenching plots of F₀/F versus [Ho(iii) complex] in the temperature range of 293–303 K. (D) The van't Hoff plot for the interaction of the Ho(iii) complex and HSA.

Fig. 11. (A) Overlap of the fluorescence spectrum of BSA (T = 298 K) and the UV absorption spectrum of the Ho(iii) complex: (a) fluorescence spectrum of BSA; (b) UV absorption spectrum of the Ho(iii) complex. (B) Overlap of the fluorescence spectrum of HSA (T = 298 K) and the UV absorption spectrum of the Ho(iii) complex: (a) fluorescence spectrum of HSA; (b) UV absorption spectrum of the Ho(iii) complex.

Fig. 12. Detailed view of the interactions between the Ho(iii) complex and (A) DNA, (B) BSA, and (C) HSA. Only the more important residues for binding are shown.

Fig. 13. Microscopic photographs of A-549 cancer cells in the absence and presence of different concentrations of the (A) Ho(iii) complex and (B) niosome nano-encapsulated Ho(iii) complex (NN-En-Ho) (concentrations are indicated by the number inside each photo).

Fig. 14. Microscopic photographs of MCF-7 cancer cells in the absence and presence of different concentrations of the (A) Ho(iii) complex and (B) niosome nano-encapsulated Ho(iii) complex (NN-En-Ho) (concentrations are indicated by the number inside each photo).