Laboratory of Inorganic Chemistry and Advanced Materials, School of Chemical Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Laboratory of Inorganic Chemistry, School of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Int J Mol Sci. 2023 Jul 24;24(14):11865. doi: 10.3390/ijms241411865.
The prospect of developing soluble and bioavailable Ti(IV) complex forms with physiological substrates, capable of influencing (patho)physiological aberrations, emerges as a challenge in the case of metabolism-related pathologies (e.g., diabetes mellitus 1 and 2). To that end, pH-specific synthetic efforts on binary Ti(IV)-(α-hydroxycarboxylic acid) systems, involving natural physiological chelator ligands (α-hydroxy isobutyric acid, D-quinic acid, 2-ethyl-2-hydroxybutyric acid) in aqueous media, led to the successful isolation of binary crystalline Ti(IV)-containing products. The new materials were physicochemically characterized by elemental analysis, FT-IR, TGA, and X-ray crystallography, revealing in all cases the presence of mononuclear Ti(IV) complexes bearing a TiO core, with three bound ligands of variable deprotonation state. Solution studies through electrospray ionization mass spectrometry (ESI-MS) revealed the nature of species arising upon dissolution of the title compounds in water, thereby formulating a solid-state-solution correlation profile necessary for further employment in biological experiments. The ensuing cytotoxicity profile (pre-adipocytes and osteoblasts) of the new materials supported their use in cell differentiation experiments, thereby unraveling their structure-specific favorable effect toward adipogenesis and mineralization through an arsenal of in vitro biological assays. Collectively, well-defined atoxic binary Ti(IV)-hydroxycaboxylato complexes, bearing bound physiological substrates, emerge as competent inducers of cell differentiation, intimately associated with cell maturation, thereby (a) associating the adipogenic (insulin mimetic properties) and osteogenic potential (mineralization) of titanium and (b) justifying further investigation into the development of a new class of multipotent titanodrugs.
开发具有生理底物的可溶性和生物可利用的 Ti(IV) 配合物形式，以影响（病理）生理异常，这在与代谢相关的病理学（例如，1 型和 2 型糖尿病）中是一项挑战。为此，在涉及天然生理螯合剂配体（α-羟基异丁酸、D-奎宁酸、2-乙基-2-羟基丁酸）的二元 Ti(IV)-(α-羟基羧酸)体系中进行了 pH 特异性的合成努力，导致成功分离出二元含 Ti(IV)的结晶产物。新的材料通过元素分析、FT-IR、TGA 和 X 射线晶体学进行了物理化学表征，在所有情况下都发现存在单核 Ti(IV)配合物，带有 TiO 核，具有可变去质子化状态的三个结合配体。通过电喷雾电离质谱（ESI-MS）进行的溶液研究揭示了标题化合物在水中溶解时产生的物种的性质，从而制定了用于进一步在生物实验中使用的固-液相关谱图。新的材料的随后的细胞毒性谱（前脂肪细胞和成骨细胞）支持它们在细胞分化实验中的使用，从而通过一系列体外生物学测定揭示了它们对脂肪生成和矿化的结构特异性有利影响。总的来说，具有明确定义的无毒二元 Ti(IV)-羟羧酸配合物，带有结合的生理底物，作为细胞分化的有效诱导剂出现，与细胞成熟密切相关，从而 (a) 与钛的成脂（胰岛素模拟特性）和成骨潜力（矿化）相关联，并且 (b) 证明了进一步研究开发一类新型多功能钛药物的合理性。
