Molecular features of CoIII tetra- and pentammines affect their influence on DNA structure

Abstract

The polyamines spermine and spermidine cause a range of structural effects on DNA. [Co(NH3)6]3+ is known to mimic many of these effects and we have shown previously that (+)[Co(en)3]3+ and (-)-[Co(en)3]3+ (en = ethylenediamine) do so as well. In this paper the effects of mono- and disubstitution of the CoIII ammines by aqua, halo and nitro groups is explored. The overall effectiveness of the amines in conferring thermal stability on the ct-DNA proceeds in the order: spermine > (+)-[Co(en)3]3+ ≈ (-)-[Co(en)3]3+ ≈ [Co(NH3)6]3+ ≈ spermidine > [Pt(NH3)4]2+ > [Co(NH3)5H2O]3+ ≈ [Co(NH3)5Cl]2+ ≈ [Co(NH3)5Br]2+ > cis-[Co(en)2NH3Cl]2+ > [Co(NH3)5(NO2)]2+ ≈ trans-[Co(NH3)4(H2O)2] 3+; whereas the B→Z transition-induction ordering is: spermine ≈ [Co(NH3)6]3+ > (+)-[Co(en)3]3+ ≈ [Co(NH3)5(H2O)]3+ > (-)-[Co(en)3]3+ > [Co(NH3)5Br]2+ > [Co(NH3)5Cl]2+, with the other amines failing to cause the transition under the 11 mM salt concentration and temperature ramp conditions used; the DNA bending ranking is: spermine > [Co(NH3)6]3+ > (+)-[Co(en)3]3+ > (-)-[Co(en)3]3+ > [Co(NH3)5(H2O)]3+ > trans-[Co(NH3)4(H2O)2] 3+ > spermidine, with the other 2+ amines (the aquo complexes will be 2+ at neutral pH), especially the bromo and nitro compounds, having comparatively little effect. While the presentation of NNN triangular faces is found to be important in the B→Z transition, the fact that the halo ligands are probably substituted by the DNA phosphates plays a role, especially in the DNA bending, where deep penetration of the major groove is concluded to be required. A favourable interaction between the backbone and the aquo ligands may enhance the B→Z transition. Show more