Interaction of rac-[M(diimine)3]2+ (M = Co, Ni) complexes with CT DNA: role of 5,6-dmp ligand on DNA binding and cleavage and cytotoxicity

Abstract

The complexes [Co(diimine)(3)](ClO(4))(2)1-3 and [Ni(diimine)(3)](ClO(4))(2)4-6, where diimine = 1,10-phenanthroline (phen) (1,4), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (2,5) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (3,6), have been isolated, characterized and their interaction with CT DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Co(5,6-dmp)(3)](ClO(4))(2)2 and rac-[Ni(5,6-dmp)(3)](ClO(4))(2)5 have been determined and the isostructural and also isomorphous complex cations possess distorted octahedral coordination geometries. The absorption spectral titrations of the complexes with DNA reveal that the CT DNA binding affinity (K(b)) of the complexes varies as 3>2>1; 6>5>4. The Ni(II) complexes display DNA binding stronger than the corresponding Co(II) analogues, which is expected of their bigger sizes. The higher DNA binding affinity of 3 and 6 is due to the involvement in partial insertion of the extended phen ring in between the DNA base pairs. In contrast, 2 and 5 interact with DNA in the major groove through hydrophobic forces involving the methyl groups on the 5,6 positions of phen ring. An enhancement in relative viscosities of DNA upon binding to 1-6 is consistent with the DNA binding affinities. The CD spectral studies show only an induced CD band on the characteristic positive band of CT DNA for both the phen (1,4) complexes. In contrast, the 5,6-dmp (2,5) and dpq (3,6) complexes bound to CT DNA exhibit biphasic CD signals in place of the positive CD band and the negative helicity band disappears. This reveals that the complexes bind to DNA enantiopreferentially and effect changes in secondary structure of DNA. The CV and DPV responses indicate that the DNA-bound dpq complexes are stabilized in the lower oxidation state of Co(II) more than in the Co(III) oxidation state. The prominent DNA cleavage abilities of 1-3 observed in the presence of H(2)O(2) (200 μM) follows the order 2>1>3 with efficiencies of more than 90% even at 10 μM complex concentration. Interestingly, Ni(II) complexes 4-6 exhibit higher cytotoxicity (IC(50): 1, 28.0; 2, 15.0; 3, 20.0; 4, 8.0; 5, 2.0; 6, 2.0 μM at 48 h; IC(50): 1, 30.0; 2, 20.0; 3, 25.0; 4, 10.0; 5, 3.0; 6, 3.0 μM at 24 h) against human breast cancer (MCF 7) cell lines than the Co(II) complexes 1-3 as well as cisplatin in spite of their inability to cleave DNA. Also, the 5,6-dmp complex 5 shows cytotoxicity higher than the dpq complex 6 at 24 h incubation time and both 5 and 6 display apoptotic and necrotic modes of cell death.

Characterization of antiproliferative potential and biological targets of a copper compound containing 4′-phenyl terpyridine

“…Despite the significant hypochromic effect (decrease in absorbance at λ max ), no bathochromicity was detected, indicating that the interaction between ZM5 and DNA does not occur by intercalation. Conversely, these data suggest an association with DNA grooves [26,27]. The hypochromic effect might result from external contact of ZM5 with doublestrand DNA.…”

Ni(ii) and Co(ii) complexes of an asymmetrical aroylhydrazone: synthesis, molecular structures, DNA binding, protein interaction, radical scavenging and cytotoxic activity

“…35,36 It has been proved that increasing the size of the substituent and planarity of ligands can enhance the DNA interaction and protein binding. 17,37,38 Therefore, planar aromatic groups, such as benzyl and napthyl group were introduced as substituent to enhance planarity of the ligand. By varying the metal center, it is possible to modify the mode as well as the extent of interaction of the complex with nucleic acids and facilitate individual applications.…”

Spectral and electrochemical studies of bis(diimine)copper(II) complexes in anionic, cationic and nonionic micelles

“…The related complexes [Cu(4-Me-phen) 2 Cl] + , [Cu(5-Me-phen) 2 Cl] + and [Cu(4-NO 2 -phen) 2 Cl] + are expected to possess a coordination geometry similar to that of [Cu(phen) 2 [54][55][56] to display a tetragonally distorted octahedral geometry in which the corners of the square plane are occupied by one nitrogen atom each of the two diimine ligands, a chloride ion and water and the axial positions by the remaining two nitrogen atoms of the diimines. The related cations [Cu(4-Me-phen) 2 [52] to possess a trigonal bipyramidal coordination structure, and the copper(II) complexes of the related ligands 4,7-dmp and 3,4,7,8-tmp are expected to have a similar coordination geometry in the solid state. All these complexes are expected to possess an octahedral geometry in aqueous solution and thus, the related cations [Cu(5,6-dmp) 2 [45][46][47][48][49][50][51][52] to display a distorted octahedral coordination geometry in which water occupies the axial position.…”

“…The related cations [Cu(4-Me-phen) 2 [52] to possess a trigonal bipyramidal coordination structure, and the copper(II) complexes of the related ligands 4,7-dmp and 3,4,7,8-tmp are expected to have a similar coordination geometry in the solid state. All these complexes are expected to possess an octahedral geometry in aqueous solution and thus, the related cations [Cu(5,6-dmp) 2 [45][46][47][48][49][50][51][52] to display a distorted octahedral coordination geometry in which water occupies the axial position. The complex cation [Cu(dpq) 2 Cl] + with a trigonal bipyramidal coordination geometry is expected to exist as [Cu(dpq) 2 (H 2 O)Cl] + species in aqueous solution.…”