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

Article abstract of DOI:10.1016/j.poly.2009.05.068

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)(O₂CCH ₂SMes)₃] (4; Mes = 2,4,6-Me₃C₆H₂) have been synthesised by the reaction of the corresponding titanium derivatives [Ti(η⁵-C₅H₅)₂Cl ₂], [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)₂Cl ₂] (R1), [Ti(η⁵-C₅H₄Me)₂Cl ₂] (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).