Facile and green synthesis of [Pd(NHC)(η3-R-allyl)Cl] complexes and their anticancer activity†

A facile and environmentally friendly method for synthesizing a range of palladium-N-heterocyclic carbene (NHC) complexes—[Pd(NHC)(η³-R-allyl)Cl]—is described. This improved approach, which is based on the use of aqueous ammonia as weak base, is effectively exemplified with different NHC structures bearing R-allyl groups, achieving good to excellent yields while significantly reducing reaction times, temperature, cost, and overall environmental impact compared to previous methods. The synthesized complexes were evaluated for in vitro anticancer activity against several human cancer cell lines. Most complexes, except those with highly bulky and lipophilic ligands, showed excellent cytotoxicity—comparable to cisplatin in cisplatin-sensitive tumors and up to 100 times more potent than the reference drug in highly aggressive or resistant cancers. Structural variations such as the type of palladium fragment or imidazol ring saturation had minimal impact on cytotoxic performance.