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

Abstract

Five complexes, [n-Bu<inf>3</inf>Sn(HLH)] (1), [n-Bu<inf>3</inf>Sn(HL4-F)] (2), [n-Bu<inf>3</inf>Sn(HL2-CF3)] (3), [n-Bu<inf>3</inf>Sn(HL3-CF3)] (4) and [n-Bu<inf>3</inf>Sn(HL4-CF3)] (5), were synthesized by reacting the corresponding azomethine- and diazenyl-functionalized hydroxy-benzoic acid pro-ligands (H'HLH, H'HL4-F, H'HL2-CF3, H'HL3-CF3 and H'HL4-CF3) with (n-Bu<inf>3</inf>Sn)<inf>2</inf>O. 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'HL3-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-Bu<inf>3</inf>Sn 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-Bu<inf>3</inf>SnO<inf>2</inf> trigonal-bipyramidal geometries, as indicated by their τ<inf>5</inf> 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'HL3-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 (IC<inf>50</inf>: 0.90–2.18 μM), with the fluorinated complex [n-Bu<inf>3</inf>Sn(HL4-F)] (2) being the most active (IC<inf>50</inf> = 0.90 ± 0.05 μM). The proposed mechanism of action is discussed in light of findings from various biological assays. © 2025 Elsevier Inc.