Expedient synthesis of N[sbnd]Oxy-Heterocyclic Carbenes (NOHC) ligands and metal complexes using mechanochemistry

Abstract

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 IC50 value of 0.75 μM, comparable to that of doxorubicin.