Effects of the tetravanadate [V4O12]4− anion on the structural, magnetic, and biological properties of copper/phenanthroline complexes

The aim to access linked tetravanadate [V4O12]4− anion with mixed copper(II) complexes, using α-amino acids and phenanthroline-derived ligands, resulted in the formation of four copper(II) complexes [Cu(dmb)(Gly)(OH2)]2[Cu(dmb)(Gly)]2[V4O12]·9H2O (1) [Cu(dmb)(Lys)]2[V4O12]·8H2O (2), [Cu(dmp)2][V4O12]·C2H5OH·11H2O (3), and [Cu(dmp)(Gly)Cl]·2H2O (4), where dmb = 4,4′-dimethioxy-2,2′-bipyridine; Gly = glycine; Lys = lysine; and dmp = 2,9-dimethyl-1,10-phenanthroline. The [V4O12]4− anion is functionalized with mixed copper(II) units in 1 and 2; while in 3, it acts as a counterion of two [Cu(dmp)]2+ units. Compound 4 crystallized as a unit that did not incorporate the vanadium cluster. All compounds present magnetic couplings arising from Cu⋯O/Cu⋯Cu bridges. Stability studies of water-soluble 3 and 4 by UV–Vis spectroscopy in cell culture medium confirmed the robustness of 3, while 4 appears to undergo ligand scrambling over time, resulting partially in the stable species [Cu(dmp)2]+ that was also identified by electrospray ionization mass spectrometry at m/z = 479. The in vitro cytotoxicity activity of 3 and 4 was determined in six cancer cell lines; the healthy cell line COS-7 was also included for comparative purposes. MCF-7 cells were more sensitive to compound 3 with an IC50 value of 12 ± 1.2 nmol. The tested compounds did not show lipid peroxidation in the TBARS assay, ruling out a mechanism of action via reactive oxygen species formation. Both compounds inhibited cell migration at 5 µM in wound-healing assays using MCF-7, PC-3, and SKLU-1 cell lines, opening a new window to study the anti-metastatic effect of mixed vanadium–copper(II) systems. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00775-023-02035-9.

units.The inset highlights the intermolecular interactions between the Cu 2+ ions and the COO -groups.

Figure S2 .
Figure S2.Crystal packing of 2. The expanded view highlights the intermolecular interactions between two independent copper(II) centers.

Figure S5 .
Figure S5.Experimental and simulated EPR spectra of 1-4 at 77 K. Compounds 1-3 were measured in the solid state, while 4 was measured in a methanol solution.

Figure S10 .
Figure S10.Models of monomeric complexes used in 1 to estimate the magnetic properties by means of CASSCF-NEVPT2-Single_Aniso calculations.

Figure S11 .
Figure S11.Models of monomeric complexes used in 2 to estimate the magnetic properties by means of CASSCF-NEVPT2-Single_Aniso calculations.

Figure S12 .
Figure S12.Models of monomeric complexes used in 3 to estimate the magnetic properties by means of CASSCF-NEVPT2-Single_Aniso calculations.

Figure S13 .
Figure S13.Models of monomeric complexes used in 4 to estimate the magnetic properties by means of CASSCF-NEVPT2-Single_Aniso calculations.

Figure S14 .
Figure S14.View of the dimeric model used in 1 to estimate the magnetic coupling constant by means of Poly_Aniso calculation on top of CASSCF-NEVPT2-Single_Aniso calculations performed on the individual Cu(II) complexes.Two equivalent models have been employed using Zn(II) (grey) and Cu(II) (golden yellow) (at the left) and Cu(II) and Zn(II) (at the right) as metal centers in the monomers.

Figure S15 .
Figure S15.View of the dimeric model used in 2 to estimate the magnetic coupling constant by means of Poly_Aniso calculation on top of CASSCF-NEVPT2-Single_Aniso calculations performed on the individual Cu(II) complexes.The same color codes are employed for Zn(II) and Cu(II) atoms.

Figure S16 .
Figure S16.View of the dimeric model used in 3 to estimate the magnetic coupling constant by means of Poly_Aniso calculation on top of CASSCF-NEVPT2-Single_Aniso calculations performed on the individual Cu(II) complexes.The same color codes are employed for Zn(II) and Cu(II) atoms.

Figure S18 .
Figure S18.Time dependent UV-Vis spectra of 3 and 4, in cell culture media.

Figure S19 .
Figure S19.Comparison of compounds 3 and 4 ESI mass spectra as fresh and aged samples.

Fig. S20 .
Fig. S20.Effect of concentration on the production of TBARS in the presence of compounds 3, 4, and dmp ligand.

Table S1 .
CShMs for the coordination environment of the Cu(II) centres of 1 and 2. The lowest SHAPE values for each ion are shown highlighted in grey.

Table S3 .
CShMs for the coordination environment of the Cu(II) centres of 3.

Table S4 .
% growth inhibitor of 3 and 4 against primary fibroblast culture

Table S6 .
Relative migration ratio % of 3 and 4 against cancer lines at different times.