Ferrocene and Its Family as Emerging Antioxidants: Experimental Evidence, Theoretical Insights, and Mechanistic Perspectives

Iron‐based organometallic compounds, ferrocenes (FcHs), exhibit excellent pharmacological activity and have been particularly studied in the areas of antitumor and antimalarial. The antioxidant properties of FcHFcHs have only begun to be assessed in the last two decades of the 21st century. To date, a large body of research has accumulated. This review offers a comprehensive analysis of experimental results evaluating FcHs as antioxidants, with emphasis on mechanistic aspects, as well as theoretical studies that identify leading FcH‐based antioxidants. The aim of this overview is also to gain a deeper understanding of the fundamental principles underlying antioxidant activity. The period covered is from 2010, when the first systematic studies appeared, until 2025. Traditional synthetic approaches for these studies, including modification of the FcH framework with various alkyls, aryls, or nitrogen‐containing heterocycles, as well as its combination with well‐known antioxidants such as di‐ tert ‐butylphenol (BHT) and tetramethylpiperidinyl‐oxyl (TEMPO) radicals, or others, were explored. Density functional theory (DFT) methods are currently used to evaluate FcH‐based compounds as potential antioxidants. Among the studied FcH antioxidants (several dozen compounds), it is difficult to identify the leading compounds due to the various evaluation methods. However, FcH amides and FcH amines, as well as hydrazides, stand out based on experimental DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) testing, CV evaluations, and DFT calculations. Apparently, the main mechanism of FcH's antioxidant properties is due to a redox transition: a single‐electron transfer (SET) from FcH to ferrocenium, and the ease and reversibility of this transfer. The organic environment in FcHs plays a significant role in charge distribution. The results of the present studies were summarized and analyzed, and it is anticipated that these findings will provide a basis for future research.