Interaction of rac-[Cu(diimine)₃]²⁺ and rac-[Zn(diimine)₃]²⁺ complexes with CT DNA: effect of fluxional Cu(II) geometry on DNA binding, ligand–promoted exciton coupling and prominent DNA cleavage

The complexes [Cu(phen)₃](ClO₄)₂1, [Cu(5,6-dmp)₃](ClO₄)₂2, [Cu(dpq)₃](ClO₄)₂3, [Zn(phen)₃](ClO₄)₂4, [Zn(5,6-dmp)₃](ClO₄)₂5 and [Zn(dpq)₃](ClO₄)₂6, where phen = 1,10-phenanthroline, 5,6-dmp = 5,6-dimethyl-1,10-phenanthroline and dpq = dipyrido[3,2-d:2′,3′-f]quinoxaline, have been isolated, characterized and their interaction with calf thymus DNA studied by using a host of physical methods. The X-ray crystal structures of rac-[Cu(5,6-dmp)₃](ClO₄)₂2 and rac-[Zn(5,6-dmp)₃](ClO₄)₂5 have been determined. While 2 possesses a regular elongated octahedral coordination geometry (REO), 5 possesses a distorted octahedral geometry. Absorption spectral titrations of the Cu(II) complexes with CT DNA reveal that the red-shift (12 nm) and DNA binding affinity of 3 (K_b, 7.5 × 10⁴ M⁻¹) are higher than those of 1 (red-shift, 6 nm; K_b, 9.6 × 10³ M⁻¹) indicating that the partial insertion of the extended phen ring of dpq ligand in between the DNA base pairs is deeper than that of phen ring. Also, 2 with a fluxional Cu(II) geometry interacts with DNA (K_b, 3.8 × 10⁴ M⁻¹) more strongly than 1 suggesting that the hydrophobic forces of interaction of 5,6 methyl groups on the phen ring is more pronounced than the partial intercalation of phen ring in the latter with a static geometry. The DNA binding affinity of 1 is lower than that of its Zn(II) analogue 4, and, interestingly, the DNA binding affinity of 2 with a fluxional geometry is higher than that of its Zn(II) analogue 5 with a spherical geometry. It is remarkable that upon binding to DNA 3 shows an increase in viscosity higher than that the intercalator EthBr does, which is consistent with the above DNA binding affinities. The CD spectra show only one induced CD band on the characteristic positive band of CT DNA upon interaction with the phen (1,4) and dpq (3,6) complexes. In contrast, the 5,6-dmp complexes 2 and 5 bound to CT DNA show exciton-coupled biphasic CD signals with 2 showing CD signals more intense than 5. The Δ-enantiomer of rac-[Cu(5,6-dmp)₃]²⁺2 binds specifically to the right-handed B-form of CT DNA at lower ionic strength (0.05 M NaCl) while the Λ-enantiomer binds specifically to the left-handed Z-form of CT DNA generated by treating the B-form with 5 M NaCl. The complex 2 is stabilized in the higher oxidation state of Cu(II) more than its phen analogue 1 upon binding to DNA suggesting the involvement of electrostatic forces in DNA interaction of the former. In contrast, 3 bound to DNA is stabilized as Cu(I) rather than the Cu(II) oxidation state due to partial intercalative interaction of the dpq ligand. The efficiencies of the complexes to oxidatively cleave pUC19 DNA vary in the order, 3 > 1 ≫ 2 with 3 effecting 100% cleavage even at 10 μM complex concentration. However, interestingly, this order is reversed when the DNA cleavage is performed using H₂O₂ as an activator and the highest cleavage efficiency of 2 is ascribed to its electrostatic interaction with the exterior phosphates of DNA.