The quest for alternative therapeutic agents with safe and effective profiles is one of the biggest challenges in oncology. Folate-targeted therapy can deliver drugs selectively into malignant cells via the Frα receptor, whereas bioorganometallic chemistry offers potential new drug candidates. Herein, novel folate γ-ferrocene (γ-Fc) conjugates were synthesized through a regiospecific route by reacting amino-terminated glutamate (Glu) γ-Fc residues with pteroyl azide (68–78% yield), and their in vitro anticancer activities were evaluated on human cells. The Fc units were attached to protected Glu residues through different linkers using amide coupling and/or “click” reactions. Cyclic voltammetry and UV-vis measurements showed that the triazole group conjugated to the Fc donates electrons to the ferrous center, which facilitates the oxidation of Fc that is responsible for the antiproliferative activity. These results were confirmed by the higher activity of folate γ-triazoleFc 21, with IC₅₀ values at 25.4 μM (±3.2) on HeLa and 21.7 μM (±0.3) on MCF-7 cells. This compound was up to 4-fold less toxic to healthy PNT2 cells and Frα-negative PC-3 cancer cells. Blocking experiments with an excess of free folic acid inhibited the folate activity suggesting their specific uptake via Frα. Glu residue analogs of folates, but lacking the pteroyl moiety, were much less toxic to cancer cells than folates. Hence, folate γ-Fcs are potential anticancer drug candidates due to their selectivity and enhanced cytotoxicity against Frα-positive malignant cells.

Recently, a new generation of polymerised ionic liquids with high thermal stability and good mechanical performances has been designed through novel and versatile cycloaliphatic epoxy-functionalised ionic liquids (CEILs). From these first promising results and unexplored chemical structures in terms of final properties of the PILs, a computational approach based on molecular dynamics simulations has been developed to generate polymer models and predict the thermo–mechanical properties (e.g., glass transition temperature and Young’s modulus) of experimentally investigated CEILs for producing multi-functional polymer materials. Here, a completely reproducible and reliable computational protocol is provided to design, test and tune poly(ionic liquids) based on epoxidised ionic liquid monomers for future multi-functional thermoset polymers.