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DNA being the necessary element in cell regeneration, controlled cellular apoptosis via DNA binding/cleaving is considered an approach to combat cancer cells. The widely prescribed metallodrug cisplatin has shown interactions with the guanine-N7 center, and a plethora of complexes are continually developed to enhance crosslinking properties as well as covalent and non-covalent interactions. Two pentadentate ligands, L1 (1-(6-(1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) and L2 (1-(6-(1-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), were synthesized together with their respective copper(II) complexes [1](ClO4)2 and [2](ClO4)2, which crystallized in a trigonal bipyramidal fashion. Different analytical and spectroscopic methods confirmed their formation, and their redox behaviour was also examined. The interactions of salmon sperm DNA (ss-DNA) with these two complexes were explored using absorbance spectroscopy, and they both exhibited a binding affinity (Kb) of ∼104 M−1. Fluorescence quenching experiments with ethidium bromide (EB)-bound DNA (EB–DNA) were also performed, and Stern–Volmer constant (KSV) values of 6.93 × 103 and 2.34 × 104 M−1 for [1](ClO4)2 and [2](ClO4)2, respectively, were obtained. Furthermore, DNA conformational changes due to the interactions of both complexes were validated via circular dichroism. We also assessed the DNA cleavage property of these complexes, which resulted in the linearization of circular plasmid DNA. This finding was supported by studying the growth of MDA-MB-231 breast cancer cells upon treatment with both Cu(II) complexes; IC50 values of 5.34 ± 1.02 μM and 0.83 ± 0.18 μM were obtained for [1](ClO4)2 and [2](ClO4)2, respectively. This validates their affinity towards DNA, and these insights can be further utilized for non-platinum based economical metallodrug development based on first row transition metals. [ABSTRACT FROM AUTHOR]

In recent years, the global perspective of small molecule activation has directed the focus towards biomimetic oxidations. Phenoxazinone synthase and catechol oxidase, two vital metalloenzymes, have drawn the attention of the scientific community towards their catalytic performances. Different transition metal-based complexes have been investigated to mimic their activities, yet many factors related to their mechanistic aspects and structure–activity relationship still lack detailed investigation. To get better insights into these factors, two penta-coordinated cis-dichloro and dibromo Cu(II) complexes [Cu(L)Cl2] 1 and [Cu(L)Br2] 2 (where L = N,N-dimethyl-4,6-di(pyridin-2-yl)-1,3,5-triazin-2-amine) were synthesized and comprehensively characterized through various spectroscopic and analytical tools such as UV-vis, FT-IR, NMR, EPR and ESI-MS. The redox behaviour of ligands as well as both the copper complexes were analysed. The molecular structure of 1 and 2 was elucidated via single-crystal X-ray diffraction analysis and a distorted square pyramidal geometry was determined. The halogen atoms (Cl for 1 and Br for 2) are found to be coordinated in a cis fashion for better substrate attachment. Catalytic performances towards the oxidation of o-aminophenol (OAPH) and 3,5-di-tert-butylcatechol (3,5-DTBC) were investigated using UV-vis spectrophotometry. Significant kinetic parameters towards the catalytic activities for 1 and 2 were determined. In terms of OAPH oxidation ability, both complexes were found to be quite comparable, with 2 having greater catalytic performance (Kcat = 156.7 h−1) than 1 (Kcat = 124.5 h−1). However, 2 shows remarkably superior activity for 3,5-DTBC oxidation (Kcat = 367.8 h−1, ∼4.5 times) than 1 (Kcat = 82.2 h−1). The mass spectrometric investigation provides information about the probable mechanistic path towards the oxidation of both the substrates. Iodometric titration experiments were performed to identify H2O2 formation, which proves the involvement of molecular O2 during the catalytic oxidation. Overall, this study offers a detailed investigation on the significance of structural lability and their profound catalytic activities for biomimetic applications, which may open a new direction toward future advancements. [ABSTRACT FROM AUTHOR]

Mixed ligand copper(II) complexes [Cu(L1)(bpy)](ClO4)21 and [Cu(L2)(bpy)](ClO4)22 (where L1 = 1-(anthracen-9-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine, L2 = 1-(pyren-1-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine and bpy = 2,2′-bipyridine) were synthesised and characterised thoroughly via different analytical and spectroscopic techniques i.e., UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, HRMS and EPR spectroscopy. The molecular structures of the synthesised complexes were obtained using the single-crystal X-ray diffraction technique. Both complexes exhibited penta-coordinated and acquired distorted square pyramidal geometry. The redox behaviour of complexes 1 and 2 was investigated by employing cyclic voltammetry. The DNA binding study was carried out by UV-vis spectrophotometry using double-stranded salmon sperm DNA (ds-ss-DNA). The binding constant (Kb) values of 1 and 2 were 0.11 × 104 M−1 and 1.05 × 104 M−1, respectively, which indicates that 2 has better binding ability than 1. This might be due to the higher conjugative abilities with the extended surface area of the aromatic pyrene ring compared to the anthracene moiety. The fluorescence quenching experiments were also performed with EB bound DNA (EB–DNA) and Stern–Volmer constant (KSV) values were calculated as 1.23 × 105 M−1 and 1.39 × 105 M−1 for 1 and 2, respectively, suggesting that 2 showed stronger interaction with ss-DNA than 1. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA varying with 1 and 2. Evaluation of the DNA binding properties of the complexes to linearized plasmid DNA indicated that 2 had modest DNA binding properties, which is a pre-requisite for a genotoxic agent. The effect of 1 and 2 on cell survival was analysed using HeLa cells by MTT assay and it was observed that the IC50 values of 1 and 2 were 43.7 μM and 18.6 μM, respectively. Our study paves the way for the designing of bio-inspired novel mixed metal complexes, which shows promising results for further exploration of molecular and mechanistic studies towards the development of non-platinum based economical metallodrugs. [ABSTRACT FROM AUTHOR]

Mononuclear Co(II) complexes [CoII(L)Cl2]; 1, [CoII(L)(bpy)Cl]PF6; 2, [CoII(L)(phen)Cl]PF6; 3 and [CoII(L)( pic) Cl]; 4, (where L = N,N-bis(pyridin-2-ylmethyl)aniline, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, pic = picolinic acid) were systematically synthesized and characterized by different analytical and spectroscopic methods. All the complexes were structurally identified by single-crystal X-ray diffraction analysis. Penta-coordinated complex 1 adopted a distorted trigonal bipyramidal geometry, whereas hexacoordinated complexes 2-4 have distorted octahedral geometry. The interactions of salmon sperm DNA (ss- DNA) with our synthesized complexes 1-4 were investigated by absorbance and fluorescence spectroscopy. All the complexes are very susceptible to DNA binding and exhibited binding affinities (Kb) in the order of ~104 M-1, indicating their strong interaction with ss-DNA. The Stern--Volmer constant (Ksv) ranged from 0.46 ± 0.01 x 104 to 1.08 ± 0.04 x 104 M-1, suggesting weak or moderate binding with DNA. Agarose gel electrophoresis revealed the DNA cleavage activity in vitro for 2-4, which could efficiently cleave the supercoiled plasmid DNA without any external agents; however, with the addition of H2O2, the cleavage property was enhanced. Live-cell imaging and other biochemical assays demonstrated the ability of Co(II) complexes 1-4 to induce significant cytotoxicity in A549 lung cancer cells with IC50 values of 32.14 ± 1.3 µM, 3.14 ± 0.16 µM, 15.78 ± 0.72 µM and 18.45 ± 0.92 µM, and in MDA-MB-231 breast cancer cells with IC50 values of 20.42 ± 0.92 µM, 0.41 ± 0.02 µM, 2.31 ± 0.12 µM and 9.67 ± 0.35 µM, respectively. [ABSTRACT FROM AUTHOR]