As an endogenous serum protein binder of Ti(IV), transferrin (Tf) serves as an excellent vehicle to stabilize the hydrolysis prone metal ion and successfully transport it into cells. This transporting role is thought to be central to Ti(IV)'s anticancer function, but efforts to synthesize Ti(IV) compounds targeting transferrin have not produced a drug. Nonetheless, the Ti(IV) transferrin complex (Ti2Tf) greatly informs on a new Ti(IV)-based anticancer drug design strategy. Ti2Tf interferes with cellular uptake of Fe(III), which is particularly detrimental to cancer cells because of their higher requirement for iron. Ti(IV) compounds of chemical transferrin mimetic (cTfm) ligands were designed to facilitate Ti(IV) activity by attenuating Fe(III) intracellular levels. In having a higher affinity for Fe(III) than Ti(IV), these ligands feature the appropriate balance between stability and lability to effectively transport Ti(IV) into cancer cells, release Ti(IV) via displacement by Fe(III), and deplete the intracellular Fe(III) levels. The cTfm ligand N,N'-di(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) was selected to explore the feasibility of the design strategy. Kinetic studies on the Fe(III) displacement process revealed that Ti(IV) can be transported and released into cells by HBED on a physiologically relevant time scale. Cell viability studies using A549 cancerous and MRC5 normal human lung cells and testing the cytotoxicity of HBED and its Ti(IV), Fe(III), and Ga(III) compounds demonstrate the importance of Fe(III) depletion in the proposed drug design strategy and the specificity of the strategy for Ti(IV) activity. The readily derivatized cTfm ligands demonstrate great promise for improved Ti(IV) anticancer drugs.

Coordination chemistry is a major component of the undergraduate inorganic chemistry curriculum, and yet, the presentation of the material can be cumbersome due to the limitations of the course typically being taught in one semester. Also, because of the large scope of this branch of chemistry encompassing all of the elements, the course design has not been standardized. These factors result in some important coordination chemistry themes being given insufficient development. Herein, we propose a novel activity to formally introduce metal complex aqueous speciation in a holistic active-learning manner that includes a lecture component and a hands-on experience. This topic has real-world relevance and contextualizes many important coordination concepts. It would extend student comprehension about the intricate factors that affect metal complexation in an aqueous solution environment by focusing on the influence of pH. The activity explores the pH dependent speciation of the well-characterized interaction between Fe­(III) and 2,3-dihydroxynapthalene-6-sulfonate and reveals the colorful changes in species throughout the pH range 0–13. Students learn how to generate speciation plots and to understand the ultraviolet–visible (UV–Vis) electronic absorption spectroscopy of transition metal compounds to be able to analyze the source of color that they observe. Assessment of the activity was conducted with 24 students who completed a Likert scale survey and responded to open-ended questions. The activity was then applied in actual course settings in which student comprehension was quantitatively evaluated. The activity can be easily adapted to students of different stages of academic development from elementary to college students.