Solving the Challenging Synthesis of Highly Cytotoxic Silver Complexes bearing Sterically Hindered NHC Ligands with Mechanochemistry

Audrey Beillard (1) , François Quintin (1) , Jérémie Gatignol (2) , Pascal Retailleau (3) , Jean-Luc Renaud (2) , Sylvain Gaillard (2) , Thomas-Xavier Métro (1) , Frédéric Lamaty (1) , Xavier Bantreil (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 LCMT - Laboratoire de chimie moléculaire et thioorganique
3 ICSN - Institut de Chimie des Substances Naturelles

The use of ball-mills enabled the straightforward synthesis of a variety of silver(I) complexes featuring challenging NHC ligands. Sterically hindered including electron-poor or with very low solubility imidazolium salts were grinded with silver(I) oxide to furnish heteroleptic or homoleptic complexes in high yield and short reaction times. The synthesis of heteroleptic bis-NHC silver(I) complexes was also performed for the first time in a ball-mill. The efficiency and rapidity of the mechanochemical approach enabled the generation of a library of unprecedented NHC silver complexes, which cytotoxicity on HCT116 colorectal cancer cell line was evaluated providing a rare example of medicinal mechanochemistry. The cationic silver complexes were found more potent than the neutral analogues, with IC50 values down to 21 nM, 256 times more potent than cisplatin.

Domaines: Chimie de coordination; Chimie thérapeutique

Audrey Beillard, François Quintin, Jérémie Gatignol, Pascal Retailleau, Jean-Luc Renaud, et al.. Solving the Challenging Synthesis of Highly Cytotoxic Silver Complexes bearing Sterically Hindered NHC Ligands with Mechanochemistry. Dalton Transactions, 2020, 49 (36), pp.12592-12598. ⟨10.1039/D0DT00410C⟩. ⟨hal-02919846⟩