Syntheses of silver and gold N-heterocyclic carbene complexes: applications in sustainable catalyses and their pharmacological activities

This doctoral project focuses on the synthesis of new organometallic silver(I) and gold(I) complexes stabilized by alkylsulfonated N‑heterocyclic carbene (NHC) ligands, specifically functionalized to clarify how the nature of the substituents influences the structural and applicational properties of the resulting systems. The work comprises an initial phase dedicated to the synthesis and characterization of these new structures through spectroscopic and mass spectrometric techniques (NMR, FT‑IR, MALDI‑MS), followed by an evaluation of their catalytic and cytotoxic potential. For the synthesis of coordinating ligands for central metals, 4,5 disubstituted imidazoles bearing various functional groups on the ring backbone were employed. The nitrogen atoms were asymmetrically functionalized: the N1 position was derivatized with benzyl or benzhydryl groups, while the N3 position was alkylated with propane- and butane-sulfonic chains. The resulting zwitterionic salts were used as precursors for N-heterocyclic carbenes. The latter were initially employed in complexation with silver(I) and subsequently converted into the corresponding gold(I) complexes via a transmetallation reaction. The novel salts and complexes were isolated, characterized, and further evaluated for catalytic and pharmacological applications. Catalytic investigations focused on three transformations: the synthesis of propiolic acid derivatives via CO₂ carboxylation of terminal alkynes, the cyclization of propargylamines to form oxazolidinones, and the A3-coupling reaction (Amine–Alkyne–Aldehyde), the latter providing the most significant results. After a preliminary solvent screening, two challenging substrates, benzaldehyde and paraformaldehyde, were evaluated. Paraformaldehyde, a polyacetal derived from formaldehyde, exhibited particularly noteworthy catalytic behavior. Under the optimized conditions, the polymeric substrate participated in the reaction only in the presence of Ag(I)/Au(I)‑NHC complexes, showing activity even at room temperature. Data analysis revealed a superior performance of the gold(I) complexes, with two structures achieving conversions up to 80% after 16 hours at room temperature. Following the catalytic studies, a preliminary evaluation of the cytotoxic activity of selected complexes and salts was carried out against two breast cancer cell lines, MCF‑7 and MDA‑MB‑231, with comparison to the healthy MCF‑10A line. The analyses were performed by the research group led by Prof. Maria Stefania Sinicropi at the University of Calabria, using the MTT assay to determine IC₅₀ values (µM) after 72 hours of exposure. The tests revealed no significant activity for the Au(I)‑NHC complexes or the zwitterionic salts, whereas the Ag(I)‑NHC complexes displayed marked cytotoxicity and promising results on both cancer cell lines. This behavior highlights a clear metal‑dependent trend favoring silver and underscores the importance of metal coordination to the N‑heterocyclic framework for biological activity. Comparative structural analysis allowed the contribution of different NHC ligand elements to be delineated. The nature of the substituents on the imidazole backbone, the length of the aliphatic sulfonated chain, and the presence of benzyl/benzhydryl groups significantly influenced the behavior of the studied systems. The experimental data, interpreted using the simplest structures as internal references, revealed meaningful correlations between structural modifications and the response of the complexes in the tested activities. Overall, the observations suggest potential optimization strategies for designing more efficient complexes for both catalytic and pharmacological applications.