The interaction of metal ions with synthetic DNA: induction of conformational and structural transitions.

The propensity of a large number of metal ions to induce cooperative conformational or structural transitions in double-stranded poly d(G-C) was assessed by UV and CD spectrometry. This ability was seen to be an intrinsic property of most metal ions. The observed (metal ion)/(polydeoxynucleotide) mole ratio calculated per G-C base pair and corresponding to the midpoints of the principal transition ranged from 0.3 (Ag(II) to 100 (Al(III)). A strong correlation was seen [y = -1.01(log x) + 3.26, r = 0.95, n = 20] between the (metal ion)/(poly d(G-C)) mole ratio required for the transition midpoint (x) and a covalent index to complex stability (y) of the metal ions. This relationship was independent of the types of transitions observed (monophasic or biphasic) or of specific conformations (e.g., B, Z, psi). The y index measures the ability of metal ions to bind to nitrogen and/or sulphur donor atoms in ligands compared to oxygen centers; equilibrium analysis indicates that the mole-ratio x decreases with increasing affinity of metal ions for poly d(G-C). Thus the observed relationship suggests that base-nitrogen binding facilitates the induced transitions. In general, metal ions designated as Class B or nitrogen/sulphur seeking (Ag(I), Hg(II), and Ru(III)) induced monophasic transitions, whereas Class A or oxygen seeking ions (La(III), Ce(III), Tb(III), Dy(III)) induced biphasic transitions. Transitions generated by ions of more ambivalent ligand preference (Borderline ions) were either monophasic (Mn(II), Fe(III), Cu(II), Cd(II), In(III), and Pb(II)) or biphasic (Cr(III), Co(II), Ni(II) and Zn(II)). Poorly defined transition-curve profiles were observed for Pt(II), Pd(II), and Al(III). Specific conformational assignments were made for some of the observed transitions. For a limited number of metal ions (Ni(II), Cu(II), Cd(II), Ag(I), Hg(II)), interaction with calf thymus DNA was similarly examined. In these instances, the susceptibility to DNase I digestion of both the DNA and polydeoxynucleotide complexes was assessed.