Developing novel zinc(<scp>ii</scp>) and copper(<scp>ii</scp>) Schiff base complexes: combined experimental and theoretical investigation on their DNA/protein binding efficacy and anticancer activity

A new versatile azide-bridged polymeric Cu(II) complex, namely, [Cu(L)(μ 1,3 -N 3 )] ∞ ( 1 ), was synthesized utilizing an N,N,O-donor piperidine-based Schiff base ligand ( E )-4-bromo-2-((2-(-1-yl)imino)methyl)phenol ( HL ), obtained via the condensation reaction of 1-(2-aminoethyl) piperidine and 5-bromo salicylaldehyde. The single-crystal X-ray diffraction analysis reveals that complex 1 consists of an end-to-end azido-bridged polymeric network, which is further rationalized with the help of a density functional theory (DFT) study. After routine characterization with a range of physicochemical studies, complex 1 is exploited to evaluate its biomedical potential. Initially, theoretical inspection with the help of a molecular docking study indicated the ability of complex 1 to effectively bind with macromolecules such as DNA and the human serum albumin (HSA) protein. The theoretical aspect was further verified by adopting several spectroscopic techniques. The electronic absorption spectroscopic analysis indicates a remarkable binding efficiency of Complex 1 with both DNA and HSA. The notable fluorescence intensity reduction of the ethidium bromide (EtBr)–DNA adduct, 4′,6-diamidino-2-phenylindole (DAPI)–DNA adduct, and HSA after the gradual addition of complex 1 authenticates its promising binding potential with the macromolecules. The retention of the canonical B form of DNA and α form of HSA during the association of complex 1 was confirmed by implementing a circular dichroism spectral study. The association ability of complex 1 with macromolecules further inspired us to inspect its impact on different cell lines such as HeLa (cervical cancer cell), PA1 (ovarian cancer cell), and HEK (normal cell). The dose-dependent and time-dependent in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay suggests an effective antiproliferative property of complex 1 with low toxicity toward the normal cell line. Finally, the anticancer activity of complex 1 toward carcinoma cell lines was analyzed by nuclear and cellular staining techniques, unveiling the cell death mechanism.

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“…2.8 Å. 36 The hydrogen-bonding parameters and other required bond parameters of complex 1 are tabulated in Tables S3–S5 .…”

Section: Results and Discussionmentioning

confidence: 99%

“…Notably, in the case of the complex with a Schiff base lacking bromine, a similar homochiral polymeric chain was obtained, but it was less tightly bound because of an apical Cu–N(azide) distance of ca. 2.8 Å . The hydrogen-bonding parameters and other required bond parameters of complex 1 are tabulated in Tables S3–S5.…”

Section: Results and Discussionmentioning

confidence: 99%

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

Das¹,

Mukherjee

Islam

et al. 2022

ACS Omega

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“…In the case of electronic absorption spectral titration, the binding constant (K) for the association of the complex with CT-DNA was calculated with the help of eq [ DNA ] / ( ε a − ε f ) = [ DNA ] / ( ε b − ε f ) + 1 / k 0.25em ( ε a − ε f ) where [DNA] represents the concentration of CT-DNA in the base pairs, “ε a ” stands for the apparent absorption coefficient corresponding to A obs /[complex 1 ], “ε f ” is the extinction coefficient of the free complex, and “ε b ” represents the extinction coefficient of the complex fully bonded with CT-DNA.…”

Section: Methodsmentioning

confidence: 99%

“…The innermetallic complexes have generally been formed in the majority of situations. However, even though it is well established that a secondary anionic residue plays a significant role in the demonstration of effective anticancer property, no report has been found in which metal–quercetin complexes have been developed bearing secondary anionic residues to examine their anticancer properties. − The metal complex’s anticancer property can be managed by carefully choosing the metal ion. Fe complexes occupy a prominent position among the many nonplatinum metal complexes.…”

Section: Introductionmentioning

confidence: 99%

DNA/Protein Binding and Apoptotic-Induced Anticancer Property of a First Time Reported Quercetin–Iron(III) Complex Having a Secondary Anionic Residue: A Combined Experimental and Theoretical Approach

Bera¹,

Das²,

Dolai³

et al. 2022

ACS Omega

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A new quercetin-based iron(III) cationic complex [Fe(Qr)Cl(H2O)(MeO)] (complex 1) is created in the current study by condensation of quercetin with ferric chloride in the presence of Et3N. Comprehensive spectroscopic analysis and conductometric measurement are used to pinpoint complex 1. The generated complex’s +3-oxidation state has been verified by electron paramagnetic resonance (EPR) research. Density functional theory analysis was used to structurally optimize the structure of complex 1. Before biomedical use, a variety of biophysical studies are implemented to evaluate the binding capacity of complex 1 with DNA and human serum albumin (HSA) protein. The findings of the electronic titration between complex 1 and DNA, as well as the stunning fall in the fluorescence intensities of the HSA and EtBr-DNA/DAPI-DNA domain after complex 1 is gradually added, give us confidence that complex 1 has a strong affinity for both macromolecules. It is interesting to note that the displacement experiment confirms partial intercalation as well as the groove binding mechanism of the title complex with DNA. The time-dependent fluorescence analysis indicates that after interaction with complex 1, HSA will exhibit static quenching. The thermodynamic parameter values in the HSA–complex 1 interaction provide evidence for the hydrophobicity-induced pathway leading to spontaneous protein–complex 1 interaction. The two macromolecules’ configurations are verified to be preserved when they are associated with complex 1, and this is done via circular dichroism spectral titration. The molecular docking investigation, which is a theoretical experiment, provides complete support for the experimental findings. The potential of the investigated complex to be an anticancer drug has been examined by employing the MTT assay technique, which is carried out on HeLa cancer cell lines and HEK-293 normal cell lines. The MTT assay results validate the ability of complex 1 to display significant anticancer properties. Finally, by using the AO/PI staining approach, the apoptotic-induced cell-killing mechanism as well as the detection of cell morphological changes has been confirmed.

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“…Metal based compounds, especially Schiff base metal complexes, offer medicinal chemistry to develop several therapeutic drugs, not fully accessible to the organic chemistry, for the treatment of a life threaten disease, cancer, due to the presence of wide variety of coordination numbers and geometries, thermodynamic and kinetic characteristics, variable oxidation states of the metal, constitutional property of cation and ligand. [1][2][3][4][5][6][7][8][9] This door had been fully opened to the chemists after successful launching of cisplatin and their analogs as the anticancer drugs and their widespread success in the clinical treatment of various forms of cancer. [10,11] But within a few years of this wonderful invention, a drive had been taken by inorganic chemists to find out new competitors against platinum-based complexes in order to reduce the side effect of the drugs (platinum metal complexes), used for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Development of DNA intercalative, HSA binder pyridine‐based novel Schiff base Cu(II), Ni(II) complexes with effective anticancer property: A combined experimental and theoretical approach

Satapathi¹,

Das²,

Rajak

et al. 2021

Applied Organom Chemis

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The two novel Cu(II) complexes [Cu(L)(CH 3 COO)] and [Cu(L)(N 3 )] (1, 2) and one Ni(II) complex [Ni(L)(N) 3 ] (3) have been developed by using the ligand HL, obtained by the condensation of 2 amino methyl pyridine and 5-bromo salicylaldehyde. All the three complexes are spectroscopically characterized along with molar conductance measurement. With the help of EPR, density functional theory (DFT) studies, the occupants of distorted square planer geometry with azide (2 and 3), acetate (1) as a secondary anionic residue, and the presence of +2 oxidation state on metal center of the complexes have been documented. After structural determination, all the complexes have been exposed to inspect their DNA and human serum albumin (HSA) binding efficacy. Initially, the higher binding constants, obtained from electronic titration among complexes and DNA, the impressive reduction of fluorescence intensities of the HSA and Ethidium Bromide (EtBr)-DNA adduct, after incremental addition of complexes separately, assure the high binding ability of complexes 2 and 3 in compare with 1. The time-dependent fluorescence study, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectral titration provide the additional support to get affirmation about the binding potentiality of the aforementioned complexes with DNA/HSA. The molecular docking study authenticates the experimental approach. Furthermore, the anticancer study of all the complexes has been checked by implementing the MTT assay method on two cancer cell lines and one normal cell line. The MTT assay results explore the better anticancer property of complex 2 in comparison with complexes 1 and 3 with low toxicity to the normal cell, and this fact may be correlated with the impressive DNA and HSA binding efficacy of complex 2.Finally, the nuclear staining study by AO/PI dual sensor discloses the nuclear morphological change of cancer cells along with the opening of cell death mechanism, suggesting the apoptotic pathway.

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Developing novel zinc(ii) and copper(ii) Schiff base complexes: combined experimental and theoretical investigation on their DNA/protein binding efficacy and anticancer activity

Abstract: Two new metal complexes namely [Zn2(LH)2(N3)4] (1) and [Cu(L)(N3)] (2) have been derived from a Schiff base ligand, (E)-2-(((2-(piperidine-2-yl)ethyl)imino)methyl)phenol (HL) employing azide as the secondary anionic residue. Single crystal structural...

Cited by 36 publications

References 77 publications

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

DNA/Protein Binding and Apoptotic-Induced Anticancer Property of a First Time Reported Quercetin–Iron(III) Complex Having a Secondary Anionic Residue: A Combined Experimental and Theoretical Approach

Development of DNA intercalative, HSA binder pyridine‐based novel Schiff base Cu(II), Ni(II) complexes with effective anticancer property: A combined experimental and theoretical approach

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