Study of the influence of the metal complex on the cytotoxic activity of titanocene-functionalized mesoporous materials

Four different titanocene complexes, [Ti(eta(5)-C5H5)(2)Cl-2] (1), [Ti(eta(5)-C5H5)(eta(5)-C5H4Pri)Cl-2] (2), [Ti(eta(5)-C5H5)(eta(5)-C5H4But)Cl-2] (3) and [Ti(eta(5)-C5H5){eta(5)-C5H3(SiMe3)(2)}Cl-2] (4), have been grafted onto dehydroxylated MCM-41 to give the novel materials MCM-41/[Ti(eta(5)-C5H5)(2)Cl-2] (S1), MCM-41/ [Ti(eta(5)-C5H5)(eta(5)-C(5)H(4)Pri)Cl-2] (S2), MCM-41/[Ti(eta(5)-C5H5)(eta(5)-C5H4But)Cl-2] (S3) and MCM-41/[Ti(eta(5)-C5H5){eta(5)-C5H3(SiMe3)(2)}Cl-2] (S4), 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. The cytotoxicity of the non-functionalized MCM-41 and S1-S4 toward human cancer cell lines, such as adenocarcinoma HeLa, human myelogenous leukemia K562 and human malignant melanoma Fem-x, has been studied. Additional studies of the toxicity of these materials on stimulated and non-stimulated peripheral blood mononuclear cells (PBMC + PHA and PBMC - PHA; i. e. normal immunocompetent cells) have been also carried out. M-50 values (quantity of material needed to inhibit normal cell growth by 50%) of the studied surfaces are reported observing that non-functionalized MCM-41 did not show notable antiproliferative activity, while the functionalized surfaces S1-S4 were active against all of the studied human cancer cells. The cytotoxic activities of surfaces S1-S3 were very similar on all the studied cancer cells, however, S4 showed M-50 values that indicate the highest activity of all the analyzed materials on all the studied cells, being two to three times more cytotoxic than S1-S3. The same tendency in the cytotoxic activity of the metal complexes 1-3 compared with 4 was observed. Taking into account that all the studied surfaces had a very similar titanium content, the activity of these surfaces strongly depends on the grafted titanocene complex (1-4). This phenomenon indicates that, in contrast with that observed by other authors, the cytotoxicity of the studied materials may be due to action of the released metal complex and is probably not due to the particle action.