Synthesis and structures of diorganotin(IV) Schiff base complexes [R2Sn(L)Cl2] and their proliferative responses on breast cancer cells

Abstract

The preparation and structural characterization in solution and the solid-state of five diorganotin(IV) complexes, namely [Me2Sn(L1)Cl2] (1), [Ph2Sn(L1)Cl2] (2), [Bn2Sn(L1)Cl2] (3), [Me2Sn(L2)Cl2] (4), [nBu2Sn(L2)Cl2] (5), [Ph2Sn(L2)Cl2] (6), and [Bn2Sn(L2)Cl2] (7), where L1 = (E)-N-(pyridin-2-ylmethylene)cyclopropanamine and L2 = (E)-N-(pyridin-2-ylmethylene)cyclohexanamine is reported. In all metal complexes the tin atoms have six-coordinate C2SnN2Cl2 environments, exhibiting two distinct configurations. Six of the seven metal complexes are related to cis-Platin concerning the distribution of the nitrogen and chlorine atoms around the metal center, with the organic substituents attached to tin occupying the axial sites. Meanwhile, the organic groups and chlorine atoms are exchanged in the diphenyltin derivative 6, giving a configuration with axial trans-oriented chlorine atoms. Aside from van der Waals contacts, the molecular arrangements in the 3D solid-state structures are controlled by weak C − H⋅⋅⋅Cl, C − H⋅⋅⋅π and/or π⋅⋅⋅π interactions, which are analyzed in a comparative manner using Hirshfeld surface and fingerprint plot analysis. Complexes 1–4, 6 and 7 were investigated by 1H, 13C and 119Sn NMR spectroscopy, with the latter confirming the hexacoordinate C2SnN2Cl2 arrangement is maintained in solution, although ligand exchange was evident for the dimethyltin complexes 1 and 4 at room temperature.The anti-proliferative activity of compounds 1–4, 6 and 7 was evaluated against the MCF-7 (human breast cancer) cell line and normal human peripheral blood lymphocytes (HPBLs) using the MTT (MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Of these, the diphenyl-substituted tin compound 2 carrying a cyclopropyl substituent at the 2-pyridylimine ligand and exhibiting an orientation of the N and Cl substituents analogous to cis-Platin demonstrated the best activity with an IC50 value of 81.63 ± 1.2 µM. Importantly, the trans-complex 6 was significantly less active (IC50 = 347.68 µM). Microscopic and colorimetric studies confirmed the triggering of apoptosis for the cell death of MCF-7, consisting of a caspase-dependent intrinsic pathway as revealed by an immunoblot study.