Expedient synthesis of NOxy-Heterocyclic Carbenes (NOHC) ligands and metal complexes using mechanochemistry

• Mechanochemistry was used to prepare 1-hydroxyimidazole 3-oxides and O-alkylated derivatives. • Novel NOHC silver complexes were mechanosynthesized in a fast and efficient multi-step process. • Gold and copper complexes were prepared by mechanotransmetalation. • Ag complex 5 displays cytotoxic activity against HCT116 cell line. 1,3-Di(benzyloxy)imidazol-2-ylidenes (or NOHCs) possess structures related to N- heterocyclic carbenes (NHCs), with potentially useful applications including the stabilization of metals. In order to prepare NOHC metal complexes, a multi-step synthesis involving mechanochemistry, and making use of ball-milling, was designed. A library of unprecedented NHOC metal complexes were tested for their cytotoxic activities against HCT116 colorectal cancer cell line. The tests demonstrated that the studied complexes displayed a similar activity, comparable with that one exhibited by the ligand. However, a remarkable activity was found in the case of silver complex 5 with an IC 50 value of 0.75 μM, comparable to that of doxorubicin. Mechanochemistry was employed as an efficient technique for the preparation of NOHCs and their metallic complexes.