On the thermodynamics of folding of an i-motif DNA in solution under favorable conditions

Under slightly acidic conditions, cytosine-rich DNA sequences can form non-canonical secondary structures called i-motifs, which occur as four stretches of cytosine repeats form hemi-protonated C·C+base pairs. The growing interest in the i-motif structures as important components in functional DNA-based nanotechnology or as potential targets of anticancer drugs, increases the need for a deep understanding of the energetics of their structural transitions. Here, a combination of spectroscopic and calorimetric techniques is used to unravel the thermodynamics of folding of an i-motif DNA under favorable conditions. The results give new insights into the energetic aspects of i-motifs and show that thermodynamic and thermal stability are related but not identical properties of such DNA structures.