Search Results (3)

We report the synthesis and biological characterization of N-heterocyclic carbene (NHC) complexes with gold(I), silver(I), copper(I), and palladium(II) metal centers, and 3-(2,6-diisopropyl-phenyl) imidazolinium- and imidazolium-based ligands, including their biscarbene complexes, along with metal complexes of 4-(S)-tert-butyl-imidazolinium-derived carbenes carrying various substituents in position 1. Compared to the imidazolium complexes, the corresponding imidazolinium complexes displayed superior cytotoxicity against the Mes-Sa uterine sarcoma cell line, while the biscarbene complexes exhibited greatly enhanced cytotoxicity with nanomolar activity. The ABCB1-overexpressing multidrug-resistant sublines of Mes-Sa demonstrated only marginal resistance to monocarbene imidazolinium complexes lacking a 4-(S)-tert-butyl group, whereas significant resistance was observed for all other complexes, with its extent further influenced by the nature of the metal center. Probing a subset of the complexes confirmed their strong cytotoxicity against the CST murine breast cancer cell line and its cisplatin-resistant variant, with little or no cross-resistance observed. Within a defined subset, compounds triggered apoptosis, and intracellular ROS production was consistently induced by the copper complexes. Collectively, these results indicate that imidazolinium-based metal NHCs are promising anticancer drug candidates, with copper and silver centers standing out for their potent cytotoxicity and evasion of both ABCB1-mediated and cisplatin resistance. Full article

Three new tridentate copper(II) N-heterocyclic carbene (NHC) complexes have been obtained and characterized with symmetrical C-4 substitutions on their pendent pyridine rings. Substitutions including methyl (Me), methoxy (OMe), and chloro (Cl) groups, which extend the library pincer Cu-NHC complexes under investigation, modify the impact of pyridinyl basicity on NCN pincer complexes. Both ligand precursors and copper(II) complexes are characterized using a range of techniques, including nuclear magnetic resonance (NMR) spectroscopy for ¹H, ¹³C, ³¹P, and ¹⁹F nuclei, electrospray ionization mass spectrometry (ESI-MS), X-ray crystallography, cyclic voltammetry, and UV-Vis spectroscopy. The pyridine substitutions lead to minimal changes to bond lengths and angles in the X-ray crystal structures of these related complexes; there is a pronounced impact on the electrochemical behavior of both the ligand precursors and copper complexes in the solution. The substitution in the pyridinyl units of these complexes show an impact on the catalytic reactivity of these complexes as applied to a model C–N bond-forming reaction (CEL cross-coupling) under well-established conditions; however, this observation does not correlate to the expected change in basicity in these ligands. Full article

Arylboronic acids are commonly used in modern organic chemistry to form new C–C and C–heteroatom bonds. These activated organic synthons show reactivity with heteroatoms in a range of substrates under ambient oxidative conditions. This broad reactivity has limited their use in protic, renewable solvents like water, ethanol, and methanol. Here, we report our efforts to study and optimize the activation of arylboronic acids by a copper(II) N-heterocyclic carbene (NHC) complex in aqueous solution and in a range of alcohols to generate phenol and aryl ethers, respectively. The optimized reactivity showcases the ability to make targeted C–O bonds, but also identifies conditions where water and alcohol activation could be limiting for C–C and C–heteroatom bond-forming reactions. This copper(II) complex shows strong reactivity toward arylboronic acid activation in aqueous medium at ambient temperature. The relationship between product formation and temperature and catalyst loading are described. Additionally, the effects of buffer, pH, base, and co-solvent are explored with respect to phenol and ether generation reactions. Characterization of the new copper(II) NCN-pincer complex by X-ray crystallography, HR-MS, cyclic voltammetry, FT-IR and UV-Vis spectral studies is reported. Full article