Synthesis,characterization and biological studies of alkenyl‐substituted titanocene(IV) carboxylate complexes

The carboxylate compounds [Ti(η⁵‐C₅H₅)(η⁵‐C₅H₄{CMe₂(CH₂CH₂CH?CH₂)})(O₂CCH₂SXyl)₂] (2; Xyl = 3,5‐Me₂C₆H₃) and [Ti(η⁵‐C₅H₅)(η⁵‐C₅H₄{CMe₂(CH₂CH₂CH?CH₂)})(O₂CCH₂SMesl)₂] (3; Mes 1 = 2,4,6‐Me₃C₆H₂) were synthesized by the reaction of [Ti(η⁵‐C₅H₅)(η⁵‐C₅H₄{CMe₂(CH₂CH₂CH?CH₂)})Cl₂] (1) with 2 equivalents of xylylthioacetic acid or mesitylthioacetic acid, respectively. Compounds 2 and 3 were characterized by spectroscopic methods. The cytotoxic activity of 1–3 was tested against human tumor cell lines from four different histogenic origins—8505C (anaplastic thyroid cancer), DLD‐1 (colon cancer) and the cisplatin sensitive A253 (head and neck cancer) and A549 (lung carcinoma)—and compared with those of the reference complex [Ti(η⁵‐C₅H₅)₂Cl₂] (R1) and cisplatin. Surprisingly, the cytotoxic activities of the carboxylate derivatives were lower than those of their corresponding dichloride analogue (1). However, complexes 1–3 were more active than titanocene dichloride against all the studied cells with the exception of complex 2 against A253 and A549 cell lines. DNA‐interaction tests were also carried out. Solutions of all the studied complexes were treated with different concentrations of fish sperm DNA, observing modifications of the UV spectra with intrinsic binding constants of 2.99 × 10⁵, 2.45 × 10⁵, and 2.35 × 10⁵ M ^?1 for 1–3. Structural studies based on density functional theory calculations of 2 and 3 were also carried out. Copyright © 2010 John Wiley & Sons, Ltd.