Synthesis, DFT calculations, and investigation of catalytic and biological activities of back‐bond functionalized re‐NHC‐Cu complexes

Abstract

Five copper complexes (3a–e) stabilized by ring‐expanded back‐bond functionalized N‐heterocyclic carbene ligands (re‐NHCs) were produced in the glovebox by reacting free re‐NHC with CuI precursor. The potential of these re‐NHC‐Cu complexes as catalysts on the synthesis of mono‐ and di‐(1,4‐disubstituted‐1,2,3‐triazoles) by Cu‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions was investigated. Various spectroscopic approaches were utilized to completely characterize the structures of the re‐Cu‐NHC complexes. Furthermore, density functional theory (DFT) calculations were carried out to get further insights into their molecular geometry and CuAAC reaction mechanism. The re‐NHC‐Cu complexes showed high activity on the CuAAC reaction in an open‐air atmosphere at rt. The Gibbs free energies as well as the optimized geometries of the intermediates and the transition states of the determining step of the reactions catalyzed by 3a, 3e, and 3b complexes were computed. Complex 3e was found to be the most efficient catalyst among these re‐NHC‐Cu complexes. Additionally, re‐Cu‐NHC complexes were investigated for their biological activities, including antiproliferative, antioxidant, AChE and TyrE inhibition, and antiparasitic activity. The results showed that the 3b, 3d, and 3e complexes possessed strong antiproliferative activity against human colon carcinoma (HCT‐116) and moderate cytotoxic activity against hepatocellular carcinoma (HepG‐2) cell lines. In addition, effective selective antileishmanial effects were observed for the 3e compound against both promastigotes and amastigotes stages of L. major with an IC50 value of 0.027 and 0.39 μM mL−1, respectively. These results demonstrate that these compounds are promising candidates for the treatment of colorectal cancer and leishmaniasis.