Copper(II) complexes of tridentate pyridylmethylethylenediamines: Role of ligand steric hindrance on DNA binding and cleavage

Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N′-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N′-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N′-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P21/n with a = 11.566(2) Å, b = 7.369(1) Å, c = 15.703(3) Å, α = 90°, β = 109.68(8)°, γ = 90° and Z = 4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1¯ with a = 9.191(2) Å, b = 12.359(3) Å, c = 14.880(3) Å, α = 79.61(13)°, β = 86.64(13)°, γ = 87.28(8)° and Z = 2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive ΔTm values (12-21 °C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.