Synthesis, Characterization, and Biological Activities of Pendant Arm‐Pyridyltetrazole Copper(II) Complexes: DNA Binding/Cleavage Activity and Cytotoxic Studies

Abstract

2-(1H-Tetrazol-5-yl)pyridine (L) has been reacted separately with Me2NCH2CH2Cl⋅HCl and ClCH2CH2OH to yield two regioisomers in each case, N,N-dimethyl-2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanamine (L1)/N,N-dimethyl-2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanamine (L2) and 2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanol (L3)/2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanol (L4), respectively. These ligands, L1-L4, have been coordinated with CuCl2 ⋅H2O in 1 : 1 composition to furnish the corresponding complexes 1-4. EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X-ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on double-stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free-radical mechanism (OH(⋅)). In vitro anticancer activities of the complexes against MCF-7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC50 values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin.

Design, Synthesis, Single X-Ray Crystal Structure, DFT and Molecular Docking Studies of Novel Clip Type-Pyridyltetrazole Analogues

“…With the compound 2 in hand we tried the reaction of the same with 0.5 equivalents of epichlorohydrine in dry DMF in the presence of K 2 CO 3 at 70 °C which furnished tetrazoles 3A and 3B and the same reaction with 1.0 equivalents of epichlorohydrine was afforded tetrazoles 3C and 3D (Scheme-I). The structure of 3A-3D were readily confirmed by observing their 13 C NMR which showed chemical shift of the tetrazole carbon atom appearing at about 152.95 or 164.59 ppm in the 1,5-and 2,5-disubstituted tetrazoles, respectively [13]. C NMR spectra of 3A which indicated a symmetric bis-tetrazole and those two sets of peaks in 3B which indicated unsymmetrical bis-tetrazole.…”

“…The synthetic route was started from picolinonitrile 1 by following the method published recently [13] to form the tetrazole 2 and the structure was confirmed by comparing the analytical data of 2 with the reported data. With the compound 2 in hand we tried the reaction of the same with 0.5 equivalents of epichlorohydrine in dry DMF in the presence of K 2 CO 3 at 70 °C which furnished tetrazoles 3A and 3B and the same reaction with 1.0 equivalents of epichlorohydrine was afforded tetrazoles 3C and 3D (Scheme-I).…”

“…Recently pyridyl-tetrazole ligands containing ester or carboxylate pendant arms were shown to form metal organic frame works [12]. Recently, we have described the synthesis of pyridyl-tetrazole compounds containing hydroxyl and dimethylamine pendant arms and examined their coordination chemistry with Cu(II) metal [13]. As part of our current investigations into the synthesis of novel pyridyltetrazole derivatives, we have altered the pendant arm and synthesized eight novel ligands in which six compounds are clip type [14] pyridyl tetrazole analogues.…”

Two related copper(I) π-complexes based on 2-allyl-5-(2-pyridyl)-2H-tetrazole ligand: Synthesis and structure of [Cu(2-apyt)NO3] and [Cu(2-apyt)(H2O)](BF4) compounds

“…In comparison to 1 and 2, there are a number of Cu(II) complexes with 2-substituted 5-(2-pyridyl)tetrazoles in which organic ligand, being attached to the metal center in the same way, produces similar five-membered rings. 29,30 Most likely an appearance of {CuN 2 C 2 } ring is the main reason of selective complexation of 2-apyt from starting mixture of 1-apyt and 2-apyt under electrochemical condition to form thermodynamically stable 1 and 2 in crystalline form. Otherwise, the presence of three nitrogen atoms with decreasing nucleophilicity in the order N4>N3>N2 and possessing higher spatial accessibility in 1-apyt should promote a considerable increase of tetrazole moiety participation in metal coordination, thus significantly reducing the contribution of chelating {CuN 2 C 2 } function.…”

Synthesis, characterization, DNA binding, cytotoxicity and molecular docking properties of three novel butterfly‐like complexes with nitrogen‐containing heterocyclic ligands

“…Besides, triazole complexes have been extensively reported in the literature for their multi‐coordinated nitrogen atoms and their unique planar structure [ 23,24 ] . However, the synthesis of metal complexes containing both triazole and pyrazine structures is rarely reported in the literature and examinations of their bioactivity are few [ 25–27 ] …”