Protection of DNA by metal ions at 95 °C: from lower critical solution temperature (LCST) behavior to coordination-driven self-assembly

While polyvalent metal ions and heating can both degrade nucleic acids, we herein report that a combination of them leads to stabilization. After incubating 4 mM various metal ions and DNA oligonucleotides at 95 °C for 3 h at pH 6 or 8, metal ions were divided into four groups based on gel electrophoresis results. Mg²⁺ can stabilize DNA at pH 6 without forming stable nanoparticles at room temperature. Co²⁺, Cu²⁺, Cd²⁺, Mn²⁺ and Zn²⁺ all protected the DNA and formed nanoparticles, whereas the nanoparticles formed with Fe²⁺ and Ni²⁺ were so stable that they remained even in the presence of EDTA. At pH 8, Ce³⁺ and Pb²⁺ showed degraded DNA bands. For Mg²⁺, better protection was achieved with higher metal and DNA concentrations. By monitoring temperature-programmed fluorescence change, a sudden drop in fluorescence intensity attributable to the lower critical solution temperature (LCST) transition of DNA was found to be around 80 °C for Mg²⁺, while this transition temperature decreased with increasing Mn²⁺ concentration. The unexpected thermal stability of DNA enabled by metal ions is useful for extending the application of DNA at high temperatures, forming coordination-driven nanomaterials, and it might offer insights into the origin of life on the early Earth.