Titanium-based therapies have emerged as a promising alternative for the treatment of cancer patients, particularly those with cisplatin resistant tumors. Unfortunately, some titanium compounds show stability and solubility problems that have hindered their use in clinical practice. Here, we designed and synthesized a new titanium complex containing a titanocene fragment, a tridentate ligand to improve its stability in water, and a long aliphatic chain, designed to facilitate a non-covalent interaction with albumin, the most abundant protein in human serum. The stability and human serum albumin affinity of the resulting titanium complex was investigated by UV–Vis absorption and fluorescence spectroscopy techniques. Complex [TiCp₂{(OOC)₂py-O-myr}] (3) (myr = C₁₄H₂₉, py = pyridine) and its analogous [TiCp₂{(OOC)₂py-OH}] (4), lacking the aliphatic chain, showed improved stability in phosphate saline buffer compared with [TiCp₂Cl₂] (1). 3 showed a strong interaction with human serum albumin in a 1:1 stoichiometry. The cytotoxic effect of 3 was higher compared to [TiCp₂Cl₂] in tumor cell lines and showed potential tumor selectivity when assayed in non-tumor human epithelial cells. Finally, 3 showed an antiproliferative effect on cancer cells, decreasing the population in the S phase, and increasing apoptotic cells in a significant manner. All this makes the novel Ti(IV) compound 3 a firm candidate to continue further studies of its therapeutic potential in vitro and in vivo.

以钛为基础的疗法已成为治疗癌症患者，尤其是顺铂耐药肿瘤患者的有希望的替代疗法。不幸的是，一些钛化合物表现出稳定性和溶解性问题，阻碍了它们在临床实践中的应用。在这里，我们设计并合成了一种新的钛络合物，其中包含一个二茂钛片段、一个三齿配体以提高其在水中的稳定性，以及一个长脂肪链，旨在促进与白蛋白（人血清中最丰富的蛋白质）的非共价相互作用。通过紫外-可见吸收和荧光光谱技术研究所得钛络合物的稳定性和人血清白蛋白亲和力。复合物 [TiCp ₂ {(OOC) ₂ py-O-myr}] ( 3 ) (myr = C₁₄ H ₂₉ , py = 吡啶) 及其类似物 [TiCp ₂ {(OOC) ₂ py-OH}] ( 4 )，缺乏脂肪链，与 [TiCp ₂ Cl ₂ ] ( 1）。图 3显示了与人血清白蛋白在 1:1 化学计量中的强相互作用。_{与肿瘤细胞系中的[TiCp 2} Cl ₂ ]相比， 3的细胞毒作用更高，并且在非肿瘤人上皮细胞中测定时显示出潜在的肿瘤选择性。最后，3显示对癌细胞的抗增殖作用，减少S期的数量，并显着增加凋亡细胞。所有这一切使新型 Ti(IV) 化合物3成为继续进一步研究其体外和体内治疗潜力的坚定候选者。