Synthesis and anticancer evaluation of tri-n-butyltin complexes featuring azomethine- and diazenyl-functionalized benzoates with peripheral fluorine against MDA-MB-231 breast cancer cells

Five complexes, [n-Bu₃Sn(HL^H)] (1), [n-Bu₃Sn(HL^4-F)] (2), [n-Bu₃Sn(HL^2-CF3)] (3), [n-Bu₃Sn(HL^3-CF3)] (4) and [n-Bu₃Sn(HL^4-CF3)] (5), were synthesized by reacting the corresponding azomethine- and diazenyl-functionalized hydroxy-benzoic acid pro-ligands (H'HL^H, H'HL^4-F, H'HL^2-CF3, H'HL^3-CF3 and H'HL^4-CF3) with (n-Bu₃Sn)₂O. Compounds 1–5 were thoroughly characterized by FT-IR and NMR (¹H, ¹³C, and ¹¹⁹Sn) spectroscopy. Additionally, the molecular and crystal structures of compounds 2, 4 and 5, along with one of their pro-ligands (H'HL^3-CF3), were determined by single-crystal X-ray diffraction analysis. The tri-n-butyltin(IV) complexes (2, 4, and 5) form mono-periodic chains in which the n-Bu₃Sn groups are linked to the oxygen atoms of the benzoate ligand through one short and one long Sn-O bond. This arrangement results in a pentacoordinated tin center, exhibiting slightly distorted trans-Bu₃SnO₂ trigonal-bipyramidal geometries, as indicated by their τ₅ parameters. The hydroxy H atom forms an intramolecular O–H···N hydrogen bond with the imine N-atom, as observed in the crystal structure of H'HL^3-CF3. The ¹¹⁹Sn NMR spectra of compounds 1–5 showed a resonance at around +110 ppm, consistent with a tetrahedral geometry in solution. This suggests that the polymeric structures of complexes 2, 4, and 5 observed in the solid state dissociate upon dissolution. The in vitro cytotoxicity of the tri-n-butyl compounds 1–5 was assessed against MDA-MB-231 breast cancer cells. Compounds 1–5 showed potent cytotoxicity against MDA-MB-231 cells (IC₅₀: 0.90–2.18 μM), with the fluorinated complex [n-Bu₃Sn(HL^4-F)] (2) being the most active (IC₅₀ = 0.90 ± 0.05 μM). The proposed mechanism of action is discussed in light of findings from various biological assays.