An unusual iminoacylation of 2-amino pyridyl thiazole: Synthesis, X-ray crystallography and DFT study of copper(II) amidine complexes and their cytotoxicity, DNA binding and cleavage study. (1st February 2019)

• Record Type: Journal Article
• Authors: Bera, Pradip; Brandão, Paula; Mondal, Gopinath; Santra, Ananyakumari; Jana, Abhimanyu; Mokhamatam, Raveendra Babu; Manna, Sunil Kumar; Mandal, Tarun Kanti; Bera, Pulakesh
• Is Part Of: Polyhedron. Volume 159(2019)
• Page Start: 436
• Page End: 445
• Publication Date: 2019-02-01
• Subjects: Pyridyl-thiazole -- Amidine complexes -- X-ray crystallography -- Cytotoxicity -- DNA cleavage; Chemistry, Inorganic -- Periodicals; Chimie inorganique -- Périodiques; Organometaalverbindingen; Anorganische chemie; 546.05
• DOI: 10.1016/j.poly.2018.11.069
• Languages: English
• ISSNs: 0277-5387

Abstract

Graphical abstract: Copper assisted acetonitrile insertion into 2-amino-4-(2-pyridyl)thiazole (HL ) conferred the nitrile to amidine transformation; an unusual formation of mono and dinuclear copper(II)-amidine complexes with the composition [Cu{L C(Me)NH)}Cl2 ] (1 ) and [(ClO4 ){L C(Me)NH)}Cu( μ -pyrazine)Cu{L C(Me)HN}(ClO4 )](ClO4 )2 (3 ). The same reaction with copper(II) perchlorate andHL yielded the complex [Cu(HL) 2 ](ClO4 )2 (2 ) where no acetonitrile addition was observed. The complexes show significant programmed cell death in human monocytic cells (U937). The chemical nuclease activities of complexes1, 2 and3 respectively show 65, 99 and 80% relaxation of supercoiled DNA at 10 μM in the presence of glutathione (GSH, 1 mM) following an oxidative cleavage mechanism. Abstract: Insertion of acetonitrile in the exocyclic NH2 group of the thiazole unit of 2-amino-4-(2-pyridyl)thiazole (HL ) in the presence of copper chloride results in the formation of the monomeric amidine complex [Cu{L C(Me)NH)}Cl2 ] (1 ). The same reaction ofHL and copper(II) perchlorate yields the complex [Cu(HL) 2 ](ClO4 )2 (2 ), without acetonitrile insertion. However, the presence of a spacer donor, e.g. pyrazine, in the reaction medium results in the formation of a dinuclear amidine derivative, [(ClO4 ){L C(Me)NH}Cu( μ -pyrazine)Cu{L C(Me)NH}(ClO4 )] (ClO4 )2 (3 ). Complexes1 and3 are the first examples of copper assisted iminoacylation of 2-amino pyridylthiazole derivatives, confirming a nitrile to amidine transformation. The new complexes were characterized by single crystal X-ray crystallography, cyclic voltammetry and a DFT study. The complexes have a potential cytotoxic effect in human monocytic cells (U937) with IC50 values ranging from 0.84 to 4.5 μM. Significant necrotic activities are ascertained by a lactate dehydrogenase (LDH) enzyme release assay. The interaction with calf thymus (CT) DNA shows the binding constant ( K b ) values are ∼10 4 M −1 . The chemical nuclease activity of1, 2 and3 result in 65, 99 and 80% relaxation of supercoiled DNA at 10 μM in the presence of glutathione (GSH, 1 mM), respectively. The study with radical scavengers proved that a hydroxyl or singlet oxygen-like species is responsible for the DNA degradation.