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Updated: May 16, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Synthesis, crystal structures and urease inhibition of Ni(II) complexes constructed from Schiff bases with
Wen-Yang Liu1, Hong-Lei Li2, Jiang-Song Jia1
1Department of Pharmacy, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University; People's Hospital of Henan University, Zhengzhou, Henan, 450003, China. SJun@zzu.edu.cn.
Abstract:
In this study, three new Ni(II) complexes, namely, [Ni(C16H13Cl2NO3)(C10H8N2)]·H2O·2CH3OH (C1), [Ni(C16H13Cl2NO3)]·3H2O·CH3OH (C2), and [Ni(C16H13Cl2NO3)(C10H8N2)]·1.5H2O (C3), were synthesized using chlorinated Schiff base ligands derived from the condensation of 3,5-dichlorosalicylaldehyde with L/D-phenylalanine, combined with Ni2+ ions and 2,2'-bipyridine as a co-ligand (for C1 and C3). All complexes C1-C3 were characterized by single-crystal X-ray diffraction and elemental analysis. This study systematically investigates the influence of co-ligands (2,2'-bipyridine vs. solvent molecules) and amino acid configurations (L-vs.D-phenylalanine) on the structural stability and urease inhibitory activity of the complexes. In vitro urease inhibitory assays showed that C1 exhibited the most potent activity (IC50 = 10.68 ± 0.09 μM), which significantly surpassed the positive control AHA (IC50 = 27.73 ± 0.33 μM), followed by C3 (IC50 = 15.49 ± 0.29 μM) and C2 (IC50 = 36.49 ± 0.13 μM). Molecular docking indicated that C1 binds to the urease active pocket stably via hydrogen bonding with HIS593 and hydrophobic interactions with ARG439/ALA440. DFT calculations revealed that the carboxyl oxygen atoms of C1 are potential electrophilic attack sites, while pyridine ring regions are prone to nucleophilic attacks. Structure-activity relationship (SAR) analysis suggested that the L-phenylalanine fragment and 2,2'-bipyridine co-ligand are crucial for enhancing urease inhibitory activity. These findings provide valuable insights for the development of novel Schiff base metal complexes as potent urease inhibitors.
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