Ultra-Short DNA Fragments Undergo A-to-B Conformational Transitions Revealed by FTIR Spectroscopy

Understanding interactions between cations and DNA is essential for elucidating the structural dynamics of this fundamental biomolecule. While B-DNA is well known to dominate in long genomic DNA under physiological ionic conditions, its stability in very short DNA fragments—particularly in dilute solutions and in crude oligonucleotide preparations—has remained largely unexplored. Previous spectroscopic studies have primarily focused on long DNA, highly purified oligonucleotides, or high-salt environments, where collective polyion effects dominate. In contrast, the present results demonstrate that even in the absence of chain overlap and under low-salt conditions, Mg2+ ions efficiently stabilize the B-form by screening phosphate–phosphate electrostatic repulsion at the intrachain level. The ability to induce an A-to-B transition in crude, ultra-short DNA fragments highlights the fundamental role of divalent counterions in governing DNA conformation and establishes a lower bound for the length scale at which B-DNA can be stabilized. These findings are particularly relevant for dilute biological systems, fragmented DNA samples, and analytical protocols where short DNA fragments and low ionic strength are unavoidable.