Triorganotin(IV) derivatives with semirigid heteroditopic hydroxo-carboxylato ligands: Synthesis, characterization, and cytotoxic properties

Three organic hydroxy-carboxylic acids separated by a semirigid aromatic diaza scaffold and carrying alkyl groups of different steric hindrance (H ' HL1, cyclopropyl; H ' HL2, cyclohexyl; H ' HL3, adamantyl) were employed as pro-ligands. Their reaction with suitable triorganotin precursors leads to 10 complexes of compositions: [Me3Sn(HL1)](n)center dot 0.5nC(6)H(5)CH(3) 1, [Et3Sn(HL1)](n) 2, [nBu(3)Sn(HL1)](n) 3, [Ph3Sn(HL1)](n) 4, [Me3Sn(HL2)](2)center dot 2CH(2)Cl(2) 5, [Et3Sn(HL2)](2) 6, {[nBu(3)Sn(HL2)][nBu(3)Sn(HL2)(H2O)]} 7, [Ph3Sn(HL2)](n)center dot nC(2)H(5)OH 8, [nBu(3)Sn(HL3)](n) 9, and [Ph3Sn(HL3)](n) 10. The solid-state structures of 1-10 were deduced from single-crystal X-ray diffraction studies along with two of the pro-ligands: H ' HL1 and H ' HL2. In the solid state, four different extended structure types were observed. In compounds 1-3 with aliphatic substituents at the tin atoms and a small substituent at the ligand backbone (cyclopropyl), 1D coordination polymers based on carboxylate bridging were observed, whereas compounds 4 and 8-10 with large substituents attached to the metal and the ligand (cyclohexyl and adamantyl) were 1D coordination polymers based on heteroditopic binding of the ligands. Albeit having essentially the same ligand conformation, the compounds having smaller substituents at the tin atoms (5, R = Me; 6, R = Et) comprise 24-membered macrocyclic ring structures. In 7, water molecules are coordinated to half the tin atoms, giving dinuclear fragments {[HL2][nBu(3)Sn][HL2][nBu(3)Sn(H2O)]}, which are linked through O-w-H center dot center dot center dot O-sal hydrogen bonds into 1D hydrogen-bonded tapes. In solution, the tin atoms in 1-10 are coordinated to a single monoanionic [HL1-3](-) ligand molecule utilizing anisobidentate coordination with the carboxylate group, as revealed from Sn-119 nuclear magnetic resonance spectral results. The antiproliferative activity of the tri-n-butyl and triphenyltin compounds 3, 4, and 7-10 was evaluated against the cervical cancer cells (HeLa) and normal kidney cells (HEK) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Of these, the adamantyl-substituted tin complexes 9 and 10 present increased activity with IC50 values of 0.51 +/- 0.01 and 0.41 +/- 0.03 (mu M) and good selectivity. The cell death mechanism was identified as apoptosis based on dual staining with fluorescent dyes (Hoechst 33342/propidium iodide and acridine orange/ethidium bromide) and might be related to reactive oxygen species.

Automated summary

In this study, three organic hydroxy-carboxylic acids with different alkyl groups were reacted with triorganotin precursors to obtain 10 complexes with varying solid-state structures. The complexes showed different coordination polymers based on the substituents attached to the tin atoms and ligands, and demonstrated potential antiproliferative activity against cervical cancer cells.