Oxidative cleavage of DNA by a dipyridoquinoxaline copper(II) complex in the presence of ascorbic acid

Complex [Cu(dpq) 2(H 2O)](ClO 4) 2.H 2O ( 1), where dpq is dipyrido-[3,2- d:2′,3′- f]-quinoxaline, has been prepared by reacting copper(II) perchlorate hexahydrate with dpq in methanol and structurally characterized. The complex crystallizes in the triclinic space group P-1 with the unit cell parameters a=8.646(2) Å, b=12.290(5) Å, c=14.283(4) Å, α=94.01(2)°, β=91.69(2)°, γ=101.60 (3)°, V=1481.7(8) Å 3 and Z=2. The structure, refined to R=0.0505 and R w =0.1441 for 5212 reflections with I>2 σ ( I) using 440 parameters, shows the presence of a CuN 4O chromophore in an axially compressed distorted trigonal–bipyramidal structure. The Cu–N distances lie in the range 1.969(3)–2.103(3) Å. The Cu–OH 2 distance is 2.145(3) Å. The complex is one-electron paramagnetic and exhibits a visible spectral d–d band at 718 nm in MeCN. It shows a quasi-reversible cyclic voltammetric response at 0.091 V (Δ E p=229 mV) at 50 mV s −1 in MeCN–0.1 M TBAP for the Cu(II)/Cu(I) couple. In 50 mM Tris–HCl/0.1 M KCl buffer–DMF mixture (1:4 v/v, pH 7.2), the couple appears at 0.089 V versus SCE. The complex undergoes facile reduction with sodium ascorbate in an aqueous DMF mixture (4:1 v/v) to form an unstable brown Cu(I) species ( λ max=440 nm, ε=7480 M −1 cm −1) which converts to 1 on exposure to air giving a turnover frequency of ca. 400. Binding studies revealed that 1 is an efficient binder to calf thymus DNA. Complex 1 on reaction with supercoiled (SC) DNA in presence of ascorbic acid in a 50 mM Tris–HCl/50 mM NaCl buffer (pH 7.2) shows nuclease activity which is 4.5 times greater than that of the phen analogue.