Macrocyclic "tet a"-Derived Cobalt(III) Complex with a N, N'-Disubstituted Hexadentate Ligand: Crystal Structure, Photonuclease Activity, and as a Photosensitizer

Murugan Sethupathi; Boobalan Thulasinathan; Nallathambi Sengottuvelan; Kumar Ponnuchamy; Franc Perdih; Arun Alagarsamy; Muthusamy Karthikeyan

doi:10.1021/acsomega.1c05306

Macrocyclic "tet a"-Derived Cobalt(III) Complex with a N, N'-Disubstituted Hexadentate Ligand: Crystal Structure, Photonuclease Activity, and as a Photosensitizer

ACS Omega. 2021 Dec 20;7(1):669-682. doi: 10.1021/acsomega.1c05306. eCollection 2022 Jan 11.

Authors

Murugan Sethupathi¹, Boobalan Thulasinathan², Nallathambi Sengottuvelan^{1

3}, Kumar Ponnuchamy⁴, Franc Perdih⁵, Arun Alagarsamy², Muthusamy Karthikeyan⁶

Affiliations

¹ Department of Industrial Chemistry, Alagappa University, Karaikudi 630003, Tamil Nadu, India.
² Department of Microbiology, Alagappa University, Karaikudi 630003, Tamil Nadu, India.
³ Department of Chemistry (DDE), Alagappa University, Karaikudi 630003, Tamil Nadu, India.
⁴ Food Chemistry and Molecular Cancer Biology Laboratory, Department of Animal Health and Management, Alagappa University, Karaikudi 630003, Tamil Nadu, India.
⁵ Faculty of Chemistry and Chemical Technology, University of Ljubljana, 1000 Ljubljana, Slovenia.
⁶ Pharmacogenomics and Computational Biology Laboratory, Department of Bioinformatics, Alagappa University, Karaikudi 630004, Tamil Nadu, India.

Abstract

A cobalt(III) complex, [Co(L)]Cl (complex 1, where L = 1,8-[N,N-bis{(3-formyl-2-hydroxy-5-methyl)benzyl}]-1,4,8,11-tetraaza-5,5,7,12,12,14-hexamethylcyclotetradecane) with distorted octahedral geometry has been synthesized and characterized using various spectroscopic techniques. The structure of the ligand has remarkably rich hydrogen intermolecular interactions such as H···H, H···C/C···H, and H···O/O···H that vary with the presence of the metal ion, and the structure of complex 1 has Cl···H interactions; this result has been proved by Hirshfeld surface and two-dimensional (2D) fingerprint maps analyses. The complex exhibits a quasi-reversible Co(III)/Co(II) redox couple with E _1/2 = -0.76 V. Calf thymus DNA (CT DNA) binding abilities of the ligand and complex 1 were confirmed by spectroscopic and electrochemical analyses. According to absorption studies, the ligand and complex 1 bind to CT DNA via intercalative binding mode, with intrinsic binding strengths of 1.41 × 10³ and 8.64 × 10³ M^-1, respectively. A gel electrophoresis assay shows that complex 1 promotes the pUC19 DNA cleavage under dark and light irradiation conditions. Complex 1 has superior antimicrobial activity than the ligand. The cytotoxicity of complex 1 was tested against MDA-MB-231 breast cancer cells with values of IC₅₀ of 1.369 μg mL^-1 in the dark and 0.9034 μg mL^-1 after light irradiation. Besides, cell morphological studies confirmed the morphological changes with AO/EB dual staining, reactive oxygen species (ROS) staining, mitochondria staining, and Hoechst staining on MDA-MB-231 cancer cells by fluorescence microscopy. Complex 1 was found to be a potent antiproliferative agent against MDA-MB-231 cells, and it can induce mitochondrial-mediated and caspase-dependent apoptosis with activation of downregulated caspases. The biotoxicity assay of complex 1 on the development of Artemia nauplii was evaluated at an IC₅₀ value of 200 μg mL^-1 and with excellent biocompatibility.