Pyrazine- and picoline-modulated unsymmetrical dipyridylamine and its copper(II) coordination polymers and tetranuclear complex: synthesis, structures and bioactivities
Journal
Journal of Molecular Structure
Journal Volume
1376
ISSN
0022-2860
Date Issued
2026-12
Author(s)
Ismayilova, Sabina Zahid
Ismayilov, Rayyat Huseyn
Song, You
Huseynova, Mansura Teyfur
Tagiyev, Dilgam Babir
Medjidov, Ajdar Akber
Yalcin, Bahattin
Sertçelik, Mustafa
Ardahanlı, Hanife
Chien, Su-Ying
Lee, Gene-Hsiang
Abstract
The unsymmetrical pyrazine-modulated ligand, N-(4-methylpyridin-2-yl)pyrazin-2-amine (Hmpypza), its 1D zig-zag chain copper(II) coordination polymer [Cu(mpypza)(O2CCH3)]n(CH3OH)0.5n 1, the tetranuclear copper(II) complex [Cu4(mpypza)2(O2CCH3)6(CH3OH)2] 2 and the 1D straight-chain copper(II) coordination polymer [Cu(Hmpypza)(NO3)2]n 3 have been successfully synthesized and structurally characterized. The free ligand Hmpypza exhibits the same anti-syn conformation, which was found earlier for the unsubstituted di(2-pyridyl)amine (Hdpa). In 1, the Hmpypza molecule acts as a tridentate ligand when it coordinates to the Cu(II) atom following deprotonation. The Cu(II) atom exhibits a square-pyramidal geometry. The tetrakis (μ-acetato)-dicopper paddle-wheel moiety is located at the center of complex 2, which features a linear chain of four penta-coordinated copper atoms. In complex 3, the Hmpypza coordinates with Cu(II) in an anti-anti conformation, functioning as a chelating bidentate ligand; the geometry around the Cu(II) atom is an extended octahedron (CuN2O4), and the distance between the copper atoms is 6.731 Å.The biological evaluation demonstrated dose-dependent antiproliferative activity against HCT116 colorectal carcinoma cells, with complex 3 exhibiting the lowest IC50 value among the tested compounds. Antifungal assays revealed selective inhibitory effects against Candida species, with activity depending on compound structure.Molecular docking studies performed against 1T8I and 5TZ1 enzymes revealed that metal coordination significantly enhances binding affinity compared to the free ligand. The copper(II) complexes displayed improved binding energies and formed multiple stabilizing interactions, including hydrogen bonds, salt bridges, π–π stacking, and hydrophobic contacts within the enzyme binding pockets. Among the investigated compounds, 2 exhibited the strongest predicted binding affinity toward both targets.
Subjects
Bioactivity
Coordination polymer
Hydrogen bonds
Magnetic properties
Modulated oligo-α-pyridylamino ligand
Spectroscopic properties
Tetranuclear copper(II) complex
Publisher
Elsevier BV
Type
journal article