Selective DNA Recognition and Cytotoxicity of Water-Soluble Helical Metallosupramolecular Polymers

Water-soluble helical Fe­(II)-based metallosupramolecular polymers ((<i>P</i>)<b>-</b> and (<i>M</i>)-polyFe) were synthesized by 1:1 complexation of Fe­(II) ions and bis­(terpyridine)­s bearing a (<i>R</i>)- and (<i>S</i>)-BINOL spacer, respectively. The binding affinity to calf thymus DNA (ct-DNA) was investigated by titration measurements. (<i>P</i>)-PolyFe with the same helicity as B-DNA showed 40-fold higher binding activity (<i>K</i>_b = 13.08 × 10⁷ M^–1) to ct-DNA than (<i>M</i>)-polyFe. The differences in binding affinity were supported by electrochemical impedance spectroscopy analysis. The charge-transfer resistance (<i>R</i>_ct) of (<i>P</i>)-polyFe increased from 2.5 to 3.9 kΩ upon DNA binding, while that of (<i>M</i>)-polyFe was nearly unchanged. These results indicate that ionically strong binding of (<i>P</i>)-polyFe to DNA chains decreased the mobility of ions in the conjugate. Unique rod-like images were obtained by atomic force microscopy measurement of the DNA conjugate with (<i>P</i>)-polyFe, likely because of the rigid binding between DNA chains and the polymer. Differences in polymer chirality lead to significantly different cytotoxicity levels in A549 cells. (<i>P</i>)-PolyFe showed higher binding affinity to B-DNA and much higher cytotoxicity than (<i>M</i>)-polyFe. The helicity in metallosupramolecular polymer chains was important not only for chiral recognition of DNA but also for coordination to a biological target in the cellular environment