Tuning the Duplex Stability of DNA Oligonucleotides Containing Metal‐Mediated Base Pairs of Imidazole‐Derived Nucleobases

Two artificial imidazole-derived nucleobases, ^HQIm (3H-imidazo[4,5-f]quinolin-5-ol) and ^CaIm (imidazole-4-carboxylate), were introduced into short DNA duplexes to systematically investigate their thermal stability upon metal ion coordination. Metal-mediated base pairs are formed with the 3d metal ions Co^II, Ni^II and Zn^II, as well as with the lanthanoid ions Eu^III and Sm^III, which induce a thermal stabilization of up to 8 °C upon binding. The latter are the first lanthanoid-mediated base pairs involving only four donor atoms that result in a significant duplex stabilization. For the 3d metal ions, the increase in DNA melting temperature is in agreement with the trend in complex stability according to the Irving-Williams series. The duplex stabilization upon metal-mediated base pair formation depends on the identity of the artificial base pair, enabling discrimination between metal ions by systematic design of the duplex. Further, the influence of pH on the stability of selected duplexes was studied, revealing a linear relation between pH and the formation of ^HQIm-Ni^II-^HQIm base pairs and allowing to induce a distinct stabilization between 1 °C and 28 °C. Regarding Eu^III-mediated base pairs, an acidic pH can be utilized to disturb their formation, presumably by promoting the coordination of Eu^III to the DNA backbone.