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

Abstract

Complex [Cu(dpq)₂(H₂O)](ClO₄)₂.H₂O (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) À, b=12.290(5) À, c=14.283(4) À, α=94.01(2)°, β=91.69(2)°,γ=101.60 (3)°, V=1481.7(8) ų and Z=2. The structure, refined to R=0.0505 and R_w=0.1441 for 5212 reflections with I>2σ (I) using 440 parameters, shows the presence of a CuN₄O chromophore in an axially compressed distorted trigonal-bipyramidal structure. The Cu-N distances lie in the range 1.969(3)-2.103(3) À. The Cu-OH₂ distance is 2.145(3) À. 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 (δE_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, =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.