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

Khushboo Iman; Md Kausar Raza; Mursaleem Ansari; Monika; Azaj Ansari; Musheer Ahmad; M. Naqi Ahamad; Khalil M. A. Qasem; Sameer Hussain; Muhammad Nadeem Akhtar; M. Shahid

doi:10.1039/D1DT00324K

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

Khushboo Iman,

^a Md Kausar Raza,^b Mursaleem Ansari,^c Monika,^d Azaj Ansari,

^d Musheer Ahmad,

^e M. Naqi Ahamad,

^a Khalil M. A. Qasem,^a Sameer Hussain,^f Muhammad Nadeem Akhtar

^g and M. Shahid

*^a

Author affiliations

* Corresponding authors

^a Functional Inorganic Materials Lab (FIML), Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India
E-mail: shahid81chem@gmail.com

^b Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India

^c Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, India

^d Department of Chemistry, Central University of Haryana, Mahendergarh 123031, Haryana, India

^e Department of Applied Chemistry (ZHCET), Aligarh Muslim University, Aligarh 202002, India

^f School of Chemistry, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China

^g Division of Inorganic Chemistry, Institute of Chemistry, Baghdad-ul-Jadeed Campus, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

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 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 {Cu₄Cd₆}] 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 {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.

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

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

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