Synthesis, photophysical properties and structures of organotin-Schiff bases utilizing aromatic amino acid from the chiral pool and evaluation of the biological perspective of a triphenyltin compound

Abstract

Five new organotin(IV) complexes of compositions [Me₂SnL¹] (1), [Me₂SnL²]_n (2), [Me₂SnL³] (3), [Ph₃SnL¹H]_n (4) and [Ph₃SnL³H] (5) (where L¹=(2S)-2-((E)-((Z)-4-hydroxypent-3-en-2-ylidene)amino)-3-(1H-indol-3-yl)propanoate, L²=(2S)-(E)-2-((2-hydroxybenzylidene)amino)-3-(1H-indol-3-yl)propanoate and L³=(2S)-(E)-2-((1-(2-hydroxyphenyl)ethylidene)amino)-3-(1H-indol-3-yl)propanoate were synthesized and spectroscopically characterized. The crystal structures of 1-4 were determined. For the dimethyltin derivative 2, a polymeric chain structure was observed as a result of a long Sn∙∙∙O contact involving the exocyclic carbonyl oxygen-atom from the tridentate ligand of a neighboring Sn-complex unit. The tin atom in this complex has a distorted octahedral coordination geometry, in which the long Sn-O bond is almost trans to the tridentate ligand nitrogen-atom. In contrast, the dimethyltin(IV) complexes 1 and 3 displayed discrete monomeric structures where the tin atom has distorted trigonal-bipyramidal geometry with the two coordinating L oxygen atoms defining the axial positions. On the other hand, 4 is a chain polymer in the solid state. The ligand-bridged Sn atoms adopt a trans-Ph₃SnO₂ trigonal-bipyramidal configuration with equatorial phenyl groups. A carboxylato oxygen atom from one and the hydroxyl oxygen of the successive ligand in the chain occupy the axial positions. The solution structures were predicted by the use of ¹¹⁹Sn NMR chemical shifts. The photophysical properties of the complexes were investigated in the solid and in solution. The triphenyltin(IV) compound 4 was tested in detail ex vivo against A375 (human melanoma) cell line, exhibiting an IC₅₀ value of 261nM to induce cell death as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay without significant alteration of cytolysis as determined by lactate dehydrogenase (LDH) assay. Compound 4-mediated potent cell death was also determined by Live and Dead assay and caspase-mediated cleavage of poly-ADP ribose polymerase (PARP). Potent cell death activity was not observed in primary cells, like blood-derived peripheral mononuclear cells (PBMC). Compound 4 inhibited the diphenyl hexatriene (DPH) binding to cells and decreased the micro viscosity in a dose-dependent manner. Additionally, the ability of 4 and cyclodextrin (CD) to interact was determined by molecular modelling.

Keywords: A375 (human melanoma) cell line; Chiral Schiff bases; Organotin(IV) compounds; Spectroscopy; Tryptophan; X-ray crystallography.