Copper(II) Complexes with Schiff Bases Derived from 2‐Pyridinecarbaldehyde N‐Oxide and Amino Acids: Studies on DNA, BSA Binding, Nuclease Activity, and Cytotoxicity

Synthesis of the first example of metal complexes containing Schiff-base ligands derived from amino acids and aldehyde with N-oxide functionality is presented. Five copper(II) complexes with the compositions [Cu(L<sup>1</sup>)(H<sub>2</sub>O)(OAc)]⋅H<sub>2</sub>O (1), [Cu<sub>3</sub>(L<sup>2</sup>)<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>O)<sub>2</sub>] (2), [Cu<sub>4</sub>(L<sup>2</sup>)<sub>2</sub>Cl<sub>6</sub>(MeOH)<sub>2</sub>] (3), [Cu<sub>2</sub>(L<sup>3</sup>)Cl<sub>3</sub>(H<sub>2</sub>O)] (4), and [Cu<sub>3</sub>(L<sup>3</sup>)<sub>2</sub>Cl<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]Cl (5) (where anionic ligands L<sup>1</sup> - L<sup>3</sup> are Schiff bases obtained by condensation of 2-pyridinecarbaldehyde N-oxide with 2-aminoisobutyric acid (HL<sup>1</sup>), β-alanine (HL<sup>2</sup>), and 3-aminobutanoic acid (HL<sup>3</sup>)) were prepared by template synthesis and fully crystallographically characterized. Complexes 1 - 4 were examined for DNA interactions, competitive studies with EB-DNA, viscosity measurements, DNA cleavage studies, cytotoxicity studies, interactions with bovine serum albumin (BSA), and theoretical docking studies. The studied complexes bind to the helix through a nonintercalative binding mode; the interaction of complexes with ctDNA is predominantly via intercalation, while viscosity measurements indicate mostly groove binding. DNA cleavage studies revealed the highest cleavage activity for complex 1. The MTT assay on three human cell lines shows the highest cytotoxic effect for complex 1 against HepG2 (human liver cancer cell line). Experimental interaction of studied complexes with BSA indicates an intermediate binding strength between complexes and albumin, while theoretical docking studies identify possible binding sites of complexes within the BSA.

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Journal
Chemistry - A European Journal
Published
2025-09-20
DOI
https://doi.org/10.1002/chem.202501578
Primary Topic
Metal complexes synthesis and properties
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article
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article

Copper(II) Complexes with Schiff Bases Derived from 2‐Pyridinecarbaldehyde N‐Oxide and Amino Acids: Studies on DNA, BSA Binding, Nuclease Activity, and Cytotoxicity

Radu L. Silaghi-Dumitrescu, Milan Gembický, Emil Švajdlenka, Thomas Schupp et al.
Chemistry - A European Journal
Metal complexes synthesis and properties
article

Copper(II) Complexes with Schiff Bases Derived from 2‐Pyridinecarbaldehyde N‐Oxide and Amino Acids: Studies on DNA, BSA Binding, Nuclease Activity, and Cytotoxicity

Radu L. Silaghi-Dumitrescu, Milan Gembický, Emil Švajdlenka, Thomas Schupp, Lucia Lintnerová, Jindra Valentová, P. Baran, Adrian Humboldt, Barbora Svitková, Alexandru Sonica, Momoka Nakashita, Kya R. Lester
article en

Abstract

Synthesis of the first example of metal complexes containing Schiff-base ligands derived from amino acids and aldehyde with N-oxide functionality is presented. Five copper(II) complexes with the compositions [Cu(L<sup>1</sup>)(H<sub>2</sub>O)(OAc)]⋅H<sub>2</sub>O (1), [Cu<sub>3</sub>(L<sup>2</sup>)<sub>2</sub>Cl<sub>4</sub>(H<sub>2</sub>O)<sub>2</sub>] (2), [Cu<sub>4</sub>(L<sup>2</sup>)<sub>2</sub>Cl<sub>6</sub>(MeOH)<sub>2</sub>] (3), [Cu<sub>2</sub>(L<sup>3</sup>)Cl<sub>3</sub>(H<sub>2</sub>O)] (4), and [Cu<sub>3</sub>(L<sup>3</sup>)<sub>2</sub>Cl<sub>3</sub>(H<sub>2</sub>O)<sub>3</sub>]Cl (5) (where anionic ligands L<sup>1</sup> - L<sup>3</sup> are Schiff bases obtained by condensation of 2-pyridinecarbaldehyde N-oxide with 2-aminoisobutyric acid (HL<sup>1</sup>), β-alanine (HL<sup>2</sup>), and 3-aminobutanoic acid (HL<sup>3</sup>)) were prepared by template synthesis and fully crystallographically characterized. Complexes 1 - 4 were examined for DNA interactions, competitive studies with EB-DNA, viscosity measurements, DNA cleavage studies, cytotoxicity studies, interactions with bovine serum albumin (BSA), and theoretical docking studies. The studied complexes bind to the helix through a nonintercalative binding mode; the interaction of complexes with ctDNA is predominantly via intercalation, while viscosity measurements indicate mostly groove binding. DNA cleavage studies revealed the highest cleavage activity for complex 1. The MTT assay on three human cell lines shows the highest cytotoxic effect for complex 1 against HepG2 (human liver cancer cell line). Experimental interaction of studied complexes with BSA indicates an intermediate binding strength between complexes and albumin, while theoretical docking studies identify possible binding sites of complexes within the BSA.

Chemistry - A European JournalVol. 31(71)
Institute of Chemistry of the Slovak Academy of Sciences (SK), Slovak Academy of Sciences (SK), Babeș-Bolyai University (RO), University of California San Diego (US), Biomedical Research Center of the Slovak Academy of Sciences (SK), Juniata College (US), FH Münster University of Applied Sciences (DE), Comenius University Bratislava (SK)
Openalex Percentile: Top 65%
Metal complexes synthesis and properties
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