Bridged NHC-Pd(II) complexes: Synthesis, DFT calculations, molecular docking, and investigation of catalytic and biological activities

Abstract

Six palladium(II) (3a-f) complexes of the type [Pd2(μ-Cl)2(NHC)] were prepared by transmetallation of the corresponding Ag-NHC and [PdCl2(CH3CN)2] complexes, and their structures were successfully characterised by 1H NMR, 13C NMR, HRMS, FTIR and elemental analysis. Density functional theory (DFT) calculations were also realised for the complexes. The prepared complexes were assessed for their catalytic activity in the C-H arylation of 2-isobuthylthiazole as well as for their biological activities. As results, these complexes were found to be potent catalysts in the creation of C5-arylated 2-isobuthylthiazole derivatives via C-H bond activation reaction. Furthermore, biological activity analysis revealed that complex 3a exhibits high cytotoxicity towards both human colon carcinoma cell lines (HCT-116) and hepatocellular carcinoma cell lines (HepG-2) with IC50 values of 4.2 and 9.3 µMmL−1, respectively. Complex 3b also showed antioxidant activity comparable to that of BHT through DPPH and ABTS assays. Both complexes 3d and 3f also showed significant inhibitory activity towards the AChE enzyme with IC50 values of 5.06 and 2.52 µMmL−1, respectively. Finally, all complexes showed excellent antiparasitic activity, with 3b exhibiting strong antileishmanial activity against both L. major promastigotes and amastigotes. The interaction between the most cytotoxic complexes and DNA, envisaged as a potential mechanism of toxicity, was explored by means of docking studies. In summary, these prepared complexes have the potential to serve as potent catalysts for the synthesis of arylated 2-isobutylthiazole and biologically active agents, paving the way for numerous prospects in the fields of medicinal chemistry and organic synthesis.