Improvement of cytotoxicity of titanocene-functionalized mesoporous materials by the increase of the titanium content

Abstract

The reaction of [Ti(η⁵-C₅H₅)₂Cl₂] (1), with 3-mercaptopropyltrimethoxysilane or 3-mercaptopropyltriethoxysilane in the presence of triethylamine leads to the formation of the thiolate complexes [Ti(η⁵-C₅H₅)₂{SCH₂CH₂CH₂Si(OMe)₃}₂] (2) and [Ti(η⁵-C₅H₅)₂{SCH₂CH₂CH₂Si(OEt)₃}₂] (3), respectively. Complexes 2 and 3 have been characterized by traditional methods, in addition, structural studies based on DFT calculations are reported. 1–3 have been grafted onto dehydroxylated MCM-41 to give the novel materials MCM-41/[Ti(η⁵-C₅H₅)₂Cl₂] (S1), MCM-41/[Ti(η⁵-C₅H₅)₂{SCH₂CH₂CH₂Si(OMe)₃}₂] (S2) and MCM-41/[Ti(η⁵-C₅H₅)₂{SCH₂CH₂CH₂Si(OEt)₃}₂] (S3) which have been characterized by powder X-ray diffraction, X-ray fluorescence, nitrogen gas sorption, multinuclear MAS NMR spectroscopy, thermogravimetry, UV spectroscopy, SEM and TEM. Materials S2 and S3 present much higher values of Ti wt% (ca. 3%) than S1 (ca. 1%), indicating the higher functionalization rate induced by the substitution of the chloro ligands by the thiolato ligands in the starting titanocene derivatives. The cytotoxicity of the non-functionalized MCM-41 and S1–S3 toward human cancer cell lines such as adenocarcinoma HeLa, human myelogenous leukemia K562 and human malignant melanoma Fem-x has been studied. In addition the cytoxicity of these materials on normal immunocompetent cells such as stimulated (PBMC+PHA) and non-stimulated (PBMC-PHA) peripheral blood mononuclear cells have been also studied. M₅₀ values (quantity of material needed to inhibit normal cell survival by 50%) of the studied surfaces show that non-functionalized MCM-41 was not active against any of the studied cells, while the functionalized surfaces S1–S3 were active against all the tested human cancer cells. The cytotoxic activity of surfaces S2 and S3 were very similar, however, S1 showed lower cytotoxic activity. This phenomenon indicates that the cytotoxicity of the titanocene-functionalized materials strongly depends on the titanium content.