Flavin-conjugated metal complexes for application in biology and catalysis

PhD Program

Speaker

Juan Sánchez-Camacho Sánchez

When

2026/04/30
11:00

Place

CFM Auditorium (Donostia / San Sebastían)

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PhD Thesis defense by Juan Sánchez-Camacho Sánchez

Supervisor: Luca Salassa (DIPC, Ikerbasque Research Professor)

Photochemistry

This thesis explores the design and reactivity of novel flavin-metal conjugates, hypothesizing that covalently tethering a redox-active isoalloxazine core to a transition metal overcomes diffusion-controlled kinetic limitations through proximal positioning. To validate the approach, three distinct metallic platforms—Pt(IV), Ru(IV), and Ir(I)—were conjugated to functionalized riboflavin derivatives and systematically investigated. First, linking flavins to Pt(IV) anticancer prodrugs enabled their rapid, reduction to bioactive Pt(II) species using endogenous electron donors, demonstrating superior efficacy compared to controls. Second, a cyclopentadienyl Ru(IV) quinoline scaffold was employed to create a bioorthogonal catalyst that successfully oxidized glutathione with enhanced redox reversibility, simultaneously mediating the activation of Pt(IV) substrates. Third, the strategy was expanded into classical homogeneous catalysis via a Ir(I)-flavin complex, providing a proof-of-concept for the synergistic activation of molecular hydrogen and subsequent intramolecular electron transfer. Across all systems, the covalent linkage proved essential. Ultimately, this work establishes a robust foundation for the rational design of dual-function bio-organometallic agents, paving the way for advanced redox-mediated chemotherapy and sustainable chemical synthesis.