Nickel-based probes of nucleic acid structure bind to guanine N7 but do not perturb a dynamic equilibrium of extrahelical guanine residues

Physical and chemical data are presented to resolve two important aspects of the mechanism and application of nucleic acid probes based on macrocyclic complexes of nickel. Direct coordination between nickel and guanine N7 had previously been suggested by the probes' sensitivity to the structural environment surrounding this nucleotide ligand. The first evidence for such recognition has now been obtained by a diagnostic ability of certain nickel complexes to convert poly(dG-dC) from a B- to Z-helix. Interaction between these complexes and 5'-GMP was also monitored by H-1 NMR and found to be characteristic of ligation between guanine N7 and nickel. Despite this mode of binding, the specificity of guanine oxidation reflects native conformations of DNA that are independent of nickel. To demonstrate this, the relative reactivity of each guanine forming an equilibrium of extrahelical bulges was shown here to mimic the distribution of species determined by previous NMR studies in the absence of nickel. Accordingly, nickel reagents may now be applied with confidence when a number of dynamic features of nucleic acid structure are examined.