Novel {Cu4} and {Cu4Cd6} clusters derived from flexible aminoalcohols: synthesis, characterization, crystal structures, and evaluation of anticancer properties. Issue 34 (10th August 2021) - Iman, Khushboo
Abstract : The effect of a heterometal on a Cu(ii ) cluster has been exercised and observed to enhance anticancer activity and apoptosis. Abstract : Two new copper clusters, {Cu4 } and {Cu4 Cd6 }, with polydentate aminoalcohol ligands, diethanol propanolamine (H3 L 1 ) and bis–tris{2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1, 3-diol} (H6 L 2 ), have been synthesized under mild conditions and characterized thoroughly by single-crystal X-ray diffraction (XRD), infrared spectroscopy, elemental analysis, powder XRD, magnetic and DFT studies, and absorption and fluorescence spectroscopy. The cluster {Cu4 } exhibits a rare tetranuclear copper cubane core whereas {Cu4 Cd6 } forms an unusual heterometallic cage owing to the introduction of the second metal Cd into the ligand. A hexapodal ligand (H6 L 2 ) with N and O donor atoms was chosen deliberately for the construction of a high-nuclearity cluster, i.e., {Cu4 Cd6 } . Interestingly, both the clusters displayed significant cytotoxicity towards human cervical (HeLa) and lung (A549) cancer cells as evident from the shallow IC50 values [15.6 ± 0.8 μM (HeLa), 18.5 ± 1.9 μM (A549) for {Cu4 }, and 11.1 ± 1.5 μM (HeLa), 10.2 ± 1.3 μM (A549) for {Cu4 Cd6 } ] obtained after a 24 h incubation. However, moderate toxicity was observed toward immortalized lung epithelial normal cells (HPL1D) with IC50 values of 32.4 ± 1.2 μM for {Cu4 } and 27.6 ± 1.7 μM for {Cu4 Cd6 } . A cellular apoptotic study using HeLa cells revealed that the {Cu4 } cluster triggered apoptosis at both the early and late phases while the {Cu4 Cd6 } cluster facilitate apoptosis mainly at the late apoptotic stage. A standard 2′, 7′-dichlorodihydrofluorescein-diacetate (DCFH-DA) test affirms that both the clusters enhanced ROS production inside the cancer cells, responsible for promoting cell apoptosis. The decanuclear {Cu4 Cd6 } clusters demonstrated better anticancer activity compared to the tetranuclear {Cu4 } clusters, indicating the role of high nuclearity and additional Cd metal in the enhanced intracellular production of ROS.