Phosphatase-like activity, DNA binding, DNAhydrolysis, anticancer and lactate dehydrogenase inhibition activity promoting by a new bis–phenanthroline dicopper(ii) complex

Abstract

A new bis-phenanthroline dicopper(II) complex has been synthesized and characterized by elemental analysis and spectroscopic methods. The molecular structure of the dinuclear Cu(II) complex [Cu₂(μ-CH₃COO)(μ-H₂O)(μ-OH)(phen)₂]²⁺ (phen = 1,10-phenanthroline) (1) was determined by single crystal X-ray diffraction technique. The coordination environment around each Cu(II) ion in complex 1 can be described as slightly distorted square pyramidal geometry. The distance between the Cu⋯Cu centers in the complex is found to be 2.987 Å. The electronic, redox, phosphate hydrolysis, DNA binding and DNA cleavage have been studied. The antiproliferative effect of complex 1 was confirmed by the lactate dehydrogenase (LDH) enzyme level in MCF-7 cancer cell lysate and content media. The dicopper(II) complex inhibited the LDH enzyme as well as the growth of the human breast cancer MCF7 cell line at an IC₅₀ value of 0.011 μg ml⁻¹. The results strongly suggest that complex 1 is a good cancer therapeutic agent. Electrochemical studies of complex 1 showed an irreversible, followed by a quasi-reversible, one electron reduction processes between −0.20 to −0.8 V. Michaelis–Menten kinetic parameters for the hydrolysis of 4-nitrophenyl phosphate by complex 1 are k_cat = 3.56 × 10⁻² s⁻¹ and K_M = 4.3 × 10⁻² M. Complex 1 shows good binding propensity to calf thymus DNA, with a binding constant value of 1.3 (±0.13) × 10⁵ M⁻¹ (s = 2.1). The size of the binding site and viscosity data suggest a DNA intercalative binding nature of the complex. Complex 1 shows efficient hydrolytic cleavage of supercoiled pBR322-DNA in the dark and in the absence of any external reagents, as demonstrated by the T4 ligase experiment. The pseudo-Michaelis–Menten kinetic parameters for DNA hydrolysis by complex 1 are k_cat = 1.27 ± 0.4 h⁻¹ and K_M = 7.7 × 10⁻² M.