Titanium(IV) carboxylate complexes: Synthesis, structural characterization and cytotoxic activity

Four titanium(IV) carboxylate complexes [Ti(η5-C5H5)2(O2CCH2SMes)2] (1), [Ti(η5-C5H4Me)2(O2CCH2SMes)2] (2), [Ti(η5-C5H5)(η5-C5H4SiMe3)(O2CCH2SMes)2] (3) and [Ti(η5-C5Me5)(O2CCH2SMes)3] (4; Mes = 2,4,6-Me3C6H2) have been synthesised by the reaction of the corresponding titanium derivatives [Ti(η5-C5H5)2Cl2], [Ti(η5-C5H4Me)2Cl2], [Ti(η5-C5H5)(η5-C5H4SiMe3)Cl2] and [Ti(η5-C5Me5)Cl3] and two (for 1–3) or three (for 4) equivalents of mesitylthioacetic acid. Complexes 1–4 have been characterized by spectroscopic methods and the molecular structure of the complexes 1, 2 and 4 have been determined by X-ray diffraction studies. The cytotoxic activity of 1–4 was tested against tumor cell lines human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, and normal immunocompetent cells, that is peripheral blood mononuclear cells PBMC and compared with those of the reference complexes [Ti(η5-C5H5)2Cl2] (R1), [Ti(η5-C5H4Me)2Cl2] (R2), [Ti(η5-C5H5)(η5-C5H4SiMe3)Cl2] (R3) and cisplatin. In all cases, the cytotoxic activity of the carboxylate derivatives was higher than that of their corresponding dichloride analogues, indicating a positive effect of the carboxylato ligand on the final anticancer activity. Complexes 1–4 are more active against K562 (IC50 values from 72.2 to 87.9 μM) than against HeLa (IC50 values from 107.2 to 142.2 μM) and Fem-x cells (IC50 values from 90.2 to 191.4 μM).

Graphical abstractA series of titanocene(IV) carboxylate complexes have been synthesised and tested against human tumor cell lines adenocarcinoma HeLa, myelogenous leukemia K562, malignant melanoma Fem-x and normal immunocompetent cells PBMC. These complexes present higher cytotoxic activity than their analogous chloride derivatives suggesting a positive effect of the carboxylato ligand in the final anticancer activity.Figure optionsDownload full-size imageDownload as PowerPoint slide