On the use of chiral compounds for probing the DNA handedness: Z to B conversion in poly(dGm5dC) upon binding of Fe(phen)3(2+) and Ru(phen)3(2+)

In order to examine whether chiral metal complexes can be used to discriminate between right- and left-handed DNA conformational states we have studied the enantioselective interactions of Fe(phen)3(2+) and Ru(phen)3(2+) (phen = 1,10-phenanthroline) with poly(dGm5dC) under B- and Z-form conditions. With the inversion-labile Fe(phen)3(2+), enantioselectivity leads to shifts in the diastereomeric binding equilibria. This effect, known as the "Pfeiffer effect" (1-4), is monitored as slowly emerging circular dichroism of the solution, corresponding to a net excess of the favoured enantiomer. With Ru(phen)3(2+), which is stable to intramolecular inversion, the difference in DNA-binding strengths of the enantiomers results in an excess of the less favoured enantiomer in the bulk solution. This excess is detected in the dialysate of the DNA/metal complex solution. With both complexes we find that the delta-enantiomer is favoured when the polynucleotide adopts the B-form, as previously shown, but also when it initially adopts the Z-form conformational state. This observation, together with evidence from UV-circular dichroism and binding data, indicates that the binding of these metal complexes induces a Z- to B-form transition in Z-form poly(dGm5dC). Consequently, neither of the studied chiral DNA-binders can easily be used to discriminate the DNA handedness.