Sustainable Catalysis and Biomedical Applications: Advancing Iron-Based Oxygen Atom Transfer through Bioinspired Ligand Design

Abstract: This review analyses innovative semi-hemic bioinspired iron (III) complexes and their utility as catalysts for oxygen atom transfer (OAT) in both chemical and photochemical contexts. The research is motivated by the biological function of human endosulfatases (e.g., HSulf1 and HSulf2), enzymes that regulate heparan sulfate (HS) sulfation—a modification with profound roles in cancer, inflammation, and related pathologies. We detail the synthesis and characterization of novel dipyrrinsupported iron complexes engineered to stabilize high-valent ironoxo intermediates, which are critical reactive species in OAT catalysis. Emphasis is placed on employing green oxidants such as dioxygen and water to promote sustainable and efficient catalytic processes consistent with environmentally benign principles. Mechanistic insights into OAT pathways, elucidated through spectroscopic techniques, reveal detailed interactions between the iron centre and substrate molecules. A primary obstacle in the field—the instability of high-valent iron intermediates—is being addressed through innovative activation strategies that enhance both catalytic reactivity and complex stability. Additionally, the review summarises progress in developing endosulfatase inhibitors, particularly sulfamate-based agents, which offer promising avenues for modulating HS sulfation patterns. By elucidating fundamental iron-catalyzed mechanisms and refining the design of selective inhibitors, this work establishes a foundation for novel therapeutic approaches targeting diseases driven by aberrant HS activity. Future directions will focus on improving inhibitor potency and selectivity, as well asinvestigating targeted delivery methods. Together, these developments not only advance the fundamental understanding of iron-mediated oxidation chemistry but also forge new connections between glycochemistry and biomedical applications.