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-BuSn(HL)] (1), [n-BuSn(HL)] (2), [n-BuSn(HL)] (3), [n-BuSn(HL)] (4) and [n-BuSn(HL)] (5), were synthesized by reacting the corresponding azomethine- and diazenyl-functionalized hydroxy-benzoic acid pro-ligands (H'HL, H'HL, H'HL, H'HL and H'HL) with (n-BuSn)O. Compounds 1-5 were thoroughly characterized by FT-IR and NMR (H, C, and Sn) spectroscopy. Additionally, the molecular and crystal structures of compounds 2, 4 and 5, along with one of their pro-ligands (H'HL), 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-BuSn 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-BuSnO trigonal-bipyramidal geometries, as indicated by their τ 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. The Sn 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: 0.90-2.18 μM), with the fluorinated complex [n-BuSn(HL)] (2) being the most active (IC = 0.90 ± 0.05 μM). The proposed mechanism of action is discussed in light of findings from various biological assays.