Novel Cu4 and Cu4Cd6 clusters derived from flexible aminoalcohols: synthesis, characterization, crystal structures, and evaluation of anticancer properties

Iman, K and Raza, MK and Ansari, M and Monika, Monika and Ansari, A and Ahmad, M and Ahamad, MN and Qasem, KMA and Hussain, S and Akhtar, MN and Shahid, M (2021) Novel Cu4 and Cu4Cd6 clusters derived from flexible aminoalcohols: synthesis, characterization, crystal structures, and evaluation of anticancer properties. In: Dalton Transactions, 50 (34). pp. 11941-11953.

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Abstract

Two new copper clusters,{Cu4}and{Cu4Cd6}, with polydentate aminoalcohol ligands, diethanol propanolamine (H3L1) and bis-tris{2-[bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol} (H6L2), 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{Cu4Cd6}forms an unusual heterometallic cage owing to the introduction of the second metal Cd into the ligand. A hexapodal ligand (H6L2) with N and O donor atoms was chosen deliberately for the construction of a high-nuclearity cluster,i.e.,{Cu4Cd6}. Interestingly, both the clusters displayed significant cytotoxicity towards human cervical (HeLa) and lung (A549) cancer cells as evident from the shallow IC50values [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{Cu4Cd6}] obtained after a 24 h incubation. However, moderate toxicity was observed toward immortalized lung epithelial normal cells (HPL1D) with IC50values of 32.4 ± 1.2 μM for{Cu4}and 27.6 ± 1.7 μM for{Cu4Cd6}. A cellular apoptotic study using HeLa cells revealed that the{Cu4}cluster triggered apoptosis at both the early and late phases while the{Cu4Cd6}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{Cu4Cd6}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. © The Royal Society of Chemistry 2021.

Item Type:	Journal Article
Publication:	Dalton Transactions
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to Royal Society of Chemistry
Keywords:	Biological organs; Cadmium; Cadmium compounds; Cell death; Copper; Copper metallography; Design for testability; Diseases; Fluorescence spectroscopy; Infrared spectroscopy; Lanthanum compounds; Ligands; Single crystals; X ray diffraction, Absorption and fluorescence spectroscopy; Anticancer activities; Anticancer properties; Cell apoptosis; Heterometallics; Hexapodal ligand; Intracellular production; Single crystal x-ray diffraction, Copper compounds
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	03 Dec 2021 07:09
Last Modified:	13 Apr 2023 07:41
URI:	https://eprints.iisc.ac.in/id/eprint/70142

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